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.

ObjectiveTo investigate the distribution characteristics and correlation of paired oral and esophageal microbiota in patients with esophageal squamous cell carcinoma （ESCC）. MethodsA total of 46 pathologically confirmed ESCC patients were enrolled， and oral swabs and cancerous tissue samples were collected. The microbial composition was analyzed using 16S rRNA gene sequencing， and bioinformatics methods were employed to compare the microbiota diversity， compositional differences， and correlations between the two sites. ResultsThe Alpha diversity of the oral microbiota in ESCC patients was significantly higher than that of their esophageal microbiota， though the overall community structure was similar between the two sites. LEfSe analysis revealed that Spirochaetes， Prevotella， Catonella， Enterococcus， Fusobacterium periodonticum， Veillonella parvula， Capnocytophaga sputigena， and Neisseria subflava were significantly enriched in ESCC tumor tissues. In contrast， Actinobacteria， Proteobacteria， Streptococcus， Neisseria， Haemophilus， Streptococcus mitis， Haemophilus parainfluenzae， Porphyromonas gingivalis， Haemophilus haemolyticus， and Prevotella tannerae were significantly enriched in the oral cavity. Correlation analysis demonstrated significant associations between the two sites at taxonomic levels such as Spirochaetes， Treponema， Granulicatella elegans， Neisseria macacae， Treponema amylovorum， Fusobacterium periodonticum， and Neisseria meningitidis （P<0.05）. ConclusionThe oral and esophageal microbiota in ESCC patients exhibit both distinct differences and similarities. Oral microbiota may influence the esophageal microenvironment through migration or local immune modulation.

Under the background of new-era technological development and the implementation of national strategies, an increasing number of national major scientific and technological infrastructures led by universities have come into operation. How to take the advantages of national facilities to serve major scientific researches while fostering innovative graduates has become an important issue in recent studies. Taking Shanghai Jiao Tong University as an example and building upon the first National Facility for Translational Medicine (Shanghai), this paper focuses on the cultivation of graduates' innovative research and practical abilities, constructs a three-dimensional collaborative education system of "institutional empowerment-knowledge transfer-capability forging, " and explores the implementation pathway through which national major scientific and technological infrastructures empower innovative talent development. Practice has demonstrated that converting the research and technological advantages of national major scientific and technological infrastructures into high-quality educational resources yields remarkable outcomes in empowering innovative talent development, offering a replicable paradigm for universities to enhance the quality of innovative talent cultivation through national multidisciplinary cross-cutting science and technology platforms such as national major scientific and technological infrastructures.

ObjectiveTo investigate the mechanism by which Sini San （SNS） treats liver fibrosis through regulating the polarization of intrahepatic Kupffer cells. MethodsSixty SPF-grade male Balb/c mice were randomized into blank control， model， silymarin （0.2 g·kg^-1）， and low-， medium-， and high-dose （2.93， 5.85， 11.70 g·kg^-1， respectively） SNS groups. A mouse model of liver fibrosis was induced by intraperitoneal injection of CCl₄. After 5 weeks of administration， the body mass， liver pathological changes ［Hematoxylin and Eosin （HE）， Masson， and Sirius red staining］， serum biochemical indicators ［alkaline phosphatase （ALP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT）］， liver fibrosis markers ［procollagen type Ⅲ （PCⅢ）， laminin （LN）， and hyaluronic acid （HA）］， inflammatory cytokines ［interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10）］， and fibrosis-related proteins ［α-smooth muscle actin （α-SMA）， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ）］ were assessed. A co-culture system of THP-1 cells （M1 macrophages） and human hepatic stellate cells （LX-2） was established. The cell experiment was designed with blank control （LX-2 alone）， model （LX-2 + M1 macrophages）， and low-， medium-， and high-dose SNS （co-culture with 5%， 10%， or 20% SNS-containing serum， respectively） groups. Cell viability， inflammatory cytokines， and macrophage phenotype were examined. Human primary hepatic Kupffer cells were allocated into blank control， M1 （LPS 100 μg·L^-1+IFN-γ 20 μg·L^-1）， M2 （IL-4 20 μg·L^-1+IL-13 20 μg·L^-1）， M1+M2， M1+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M1 conditions for 24 h）， M2+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M2 conditions for 24 h）， and M1+M2+SNS groups （supplemented with 10% SNS-containing serum for 2 h after culture under M1+M2 conditions for 24 h）， and the expression of nuclear factor-κB （NF-κB） p65 and signal transducer and activator of transcription 3 （STAT3） at protein and mRNA levels was determined. ResultsCompared with the blank group， the model group exhibited increased serum levels of ALT， AST， ALP， PCⅢ， LN， HA， IL-6， and TNF-α， upregulated protein and mRNA levels of α-SMA， Col Ⅰ， and Col Ⅲ in the liver tissue （P<0.05， P<0.01）， and decreased IL-10 level and STAT3 mRNA level （P<0.05， P<0.01）， accompanied by marked collagen deposition and inflammatory infiltration in the liver. Compared with the model group， all doses of Sini San reversed these alterations （P<0.05， P<0.01）， with the high-dose group showing the most pronounced effects. Cell experiments demonstrated that， compared with the blank control group， the model group had elevated levels of pro-inflammatory cytokines （IL-1β， IL-6， and TNF-α） and upregulated protein and mRNA levels of M1 markers ［cluster of differentiation 86 （CD86， inducible nitric oxide synthase （iNOS）， and monocyte chemoattractant protein-1 （MCP-1）］ （P<0.01）， along with declined level of IL-10 and downregulated expression of M2 markers ［（CD163， CD206， and arginase-1 （Arg-1）］ （P<0.05，P<0.01）. Compared with the model group， treatment with Sini San-containing serum at various concentrations lowered the levels of pro-inflammatory cytokines and expression of M1 markers （P<0.05， P<0.01）， while increasing the IL-10 level and M2 marker expression （P<0.05， P<0.01）. Additionally， Sini San downregulated the mRNA level of NF-κB and upregulated the mRNA level of STAT （P<0.05， P<0.01）. In the experiment with human primary Kupffer cells， compared with the blank group， the M1 group showed increased NF-κB p65 expression （P<0.01） and decreased STAT3 expression （P<0.05）， whereas the M2 group exhibited increased STAT3 expression （P<0.01）. Compared with the respective model groups， Sini San-containing serum reversed the M1-induced overexpression of NF-κB p65 （P<0.05， P<0.01） and further enhanced the M2-induced STAT3 expression （P<0.05， P<0.01）. ConclusionSini San can inhibit the NF-κB p65/STAT3 signaling pathway and repolarize intrahepatic Kupffer cells from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype to attenuate inflammation and suppress hepatic stellate cell activation and collagen deposition， thereby exerting anti-fibrotic effect.

Objective:To investigate tetanus antibody levels and distribution characteristics in a healthy population of Henan Province.Methods:A cross-sectional survey was conducted in Henan Province from 2022 to 2023 to investigate the permanent population. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-tetanus toxoid IgG antibody (anti-TT), and the positive rate (≥0.01 IU/ml), protection rate (≥0.1 IU/ml) and concentration differences of tetanus antibodies in different populations were analyzed.Results:The age M ( Q1, Q3) of 5 494 participants was 14 (4, 40) years old, with a minimum age of 8 months and a maximum age of 81 years old. The male-to-female ratio was 1.00∶1.18. The total positive rate, protective rate and mean concentration (MC) [ M ( Q1, Q3)] of Anti-TT were 76.48%, 41.72% and 0.067 (0.010, 0.154) IU/ml, respectively. The positive rates of Anti-TT in individuals aged <3, 3-5, 6-9, and 10-14 were 95.32%, 96.05%, 97.81%, and 93.17%, respectively, but gradually decreased with age ( χ2trend=1 283.02, P<0.001). The antibody protection rate [82.13% (579/705)] and MC [ M ( Q1, Q3) of 0.160 (0.122, 0.259) IU/ml] in the population under 3 years old were relatively high, and both showed a decreasing trend with age (protection rate: χ2trend=1 889.49, P<0.001; MC: t=-54.22, P<0.001). There were significant differences in antibody levels among populations of different ages, regions, occupations, and immunization histories (all P<0.001). Within 13 years after the last dose of TTCV vaccination, the positive rate of Anti-TT was all greater than 90%, but the protection rate and MC continued to decrease with the prolongation of vaccination time (protection rate: χ2trend=160.58, P<0.001; MC: t=-14.93, P<0.001). After the last dose of vaccination, the protection rate and MC [ M ( Q1, Q3)] decreased to 30.43% and 0.055 (0.036, 0.115) IU/ml, respectively, for 10-13 years. The protection rates of Anti-TT for farmers, workers, people aged 60 and above, and women of childbearing age (20-45 years old) were 7.77%, 22.96%, 8.39%, and 12.72%, respectively. Conclusion:The level of tetanus antibodies in infants and young children in Henan Province is relatively high from 2022 to 2023, but it decreases with age and prolonged post-immunization time. There are significant differences in antibody levels among individuals of different ages, regions, occupations, and immunization histories. Occupational high-risk groups such as farmers and workers, elderly people, and women of childbearing age lack sufficient immunization protection.

Objective:Analyze the imaging and clinical data of cases undergoing thoracoscopic subsegmental resection for non-small cell lung cancer(NSCLC) with a diameter≤2 cm, and explore the clinical outcomes of subsegmental resection.Methods:A retrospective analysis was conducted on the clinical data of 58 patients who underwent thoracoscopic subsegmentectomy in China-Japan Friendship Hospital from January 2020 to July 2024. Three-dimensional reconstruction technology was used for surgical planning before the operation, and thoracoscopic subsegmentectomy was performed, including single lung subsegmentectomy(Group 1), multiple lung subsegmentectomy(Group 2), and combined segmentectomy and subsegmentectomy(Group 3).Results:All patients successfully completed the surgery, with 23 cases of single lung subsegmentectomy, 6 cases of multiple lung subsegmentectomy, and 29 cases of combined segmentectomy and subsegmentectomy. The median intraoperative blood loss was 30.0(20.0, 30.0)ml, the average operation time was(2.03±0.68) h, the average pathological size of the nodules was(10.53±4.45) mm, and the average postoperative tube retention was(2.55±0.92) days. There were 6 cases of postoperative complications, including pulmonary air leakage in 2 cases, cerebral embolism in 1 case, pulmonary embolism in 1 case, pulmonary infection in 1 case, and atrial fibrillation in 1 case. All patients had negative surgical margins in the postoperative pathology. Group 1 had less average intraoperative blood loss than Group 2, with statistically significant differences( P=0.027). Surgical procedures for the upper lobe of the lung mainly involve the resection of combined segments and subsegments, while those for the lower lobe primarily consist of single segmentectomy. Conclusion:Subsegmentectomy is an effective surgical approach when the nodule is small and a clear margin can be ensured, allowing for better preservation of remaining lung tissue. Bleeding during multiple subsegmentectomies is greater than that in single subsegmentectomy and combined segmentectomy with subsegmentectomy, which may be related to the more complex vascular variations in multiple subsegmentectomies.

Objective:To systematically search and summarize high-quality evidence-based evidence on the prevention and management of refeeding syndrome in patients with anorexia nervosa, and to provide a basis for preventive management of patients at high risk.Methods:A computerized search was conducted for evidence on the prevention and management of refeeding syndrome in patients with anorexia nervosa in relevant domestic and international databases and professional team websites, including clinical decision-making, guidelines, expert consensus, evidence summaries and systematic evaluations, and randomized controls. The search timeframe was from database construction to August 2024. Two researchers trained in systematic evidence-based knowledge independently performed literature screening, quality assessment, and extraction and summarization of evidence according to inclusion and exclusion criteria.Results:A total of 15 publications were included, which contained 4 guidelines, 3 expert consensus, 3 clinical decision-making, 3 systematic evaluations, and 2 randomized control trials. Thirty-one pieces of evidence for the prevention and management of refeeding syndrome were summarized in seven areas: treatment team, risk factors, risk assessment, preventive measures, clinical diagnosis, management measures, and patient safety.Conclusions:The best evidence summarized in this study for the prevention and management of refeeding syndrome in anorexia nervosa provides an evidence-based basis for practitioners to implement refeeding syndrome prevention and management measures.

Objective:The differentially expressed genes(DEGs)and activated signaling pathways in systemic sclerosis(SSc)were screened by bioinformatics methods,and Chinese medicines for potential treatment of SSc were explored,providing a new theoretical basis for the study of SSc and the screening of potential markers.Methods:The data sets GSE58095,GSE130953,GSE33463 and GSE58613 were selected from GEO database and divided into skin group and peripheral blood group according to the sample source.The DEGs of SSc patients was analyzed by R language,and the Wayne diagram was drawn to take the intersection of the two groups.Metascape was used for GO enrichment analysis and KEGG pathway enrichment analysis,and STRING and Cytoscape were used for protein interaction network analysis to find key pathways and hub genes.The core genes were mapped to the medical on-tology information retrieval platform,and related Chinese medicines for SSc treatment were screened.The effective components of Chi-nese medicines were obtained through TCMSP and HERB databases,and the target letters of active ingredients were obtained through swiss database.The"drug-active ingredient-target"network was constructed by Cytoscape.Results:Total 218 DEGs were identified from the skin group of patients with SSc,and 283 DEGs were screened from peripheral blood of patients with SSc.Among them,there were 7 DEGs co-upregulated in skin and peripheral blood,namely ISG15,LGALS3BP,BST2,C1QB,IFI27,CEACAM1 and FBP1.CAMK2N1 was up-regulated in skin but down-regulated in peripheral blood,ARG1 was down-regulated in skin but up-regulated in pe-ripheral blood.GO and KEGG analysis of SSc DEGs showed that these genes were significantly enriched in inflammatory response,he-moglobin complex,immune receptor activity and extracellular matrix.The results of protein interaction network suggest that more than 10 genes such as COL1A1,CTGF12,IL1B,IFNG and JUN may be potential markers of SSc and core genes of therapeutic targets.The potential Chinese medicines screened for SSc treatment include ginseng,sanguisorba,convolvula,wolfberry,safflower,etc.The main components of these herbs were β-sitosterol,quercetin,kaempferol,stigmasterol,luteolin,sitosterol,Spinasterol,and the target were AKR1B1,AR,CYP1B1,XDH,etc.Conclusion:This study uses bioinformatics to screen out core genes that may be potential markers and therapeutic targets for SSc,which is expected to be a new target for the early diagnosis and mechanism research of SSc.Meanwhile,the mapped Chinese medicine and its effective components can provide ideas for the research and development of Chinese medicine compounds for the treatment of SSc.

Objective To assess the efficacy of endoscopic transethmoidal orbital wall decompression(ETMOWD)in conjunction with fat removal orbital decompression(FROD)on restrictive strabismus in patients with thyroid-associated ophthalmopathy(TAO).Methods A retrospective case series study was conducted involving patients diagnosed with TAO at our hospital from December 2021 to August 2024.Patients were divided into two groups:the orbital decompression group(OD group)and the non-orbital decompression group(NOD group),based on whether they underwent orbital decompression surgery.The study compared perioperative data,types of strabis-mus,degree of ocular motility limitation,extent of posterior migration of ocular muscles,and postoperative outcomes between the two groups.Additionally,the effects of ETMOWD combined with FROD on strabismus were evaluated by analyzing changes in relevant indices before and after surgery in the OD group.Results A total of 65 participants were included in the analysis,with 40 in the OD group group and 25 in the NOD group.There was no statistically significant difference in baseline characteristics between the two groups.Preoperative strabismus types,including horizontal and vertical strabismus,did not differ significantly between the OD and NOD groups(P>0.05).However,the mean preoperative restriction grade of eye movement was significantly higher in the OD group compared to the NOD group.Additionally,the number of surgeries,mean total operated muscles,and number of horizontal muscles were all significantly higher in the OD group than in the NOD group(all P<0.05),with a notably different effect on horizontal muscle migration between the two groups.The degree of restriction of eye movement and diplopia improved significantly in all patients,with cure rates of 70%in the OD group and 72%in the NOD group.Furthermore,the OD group underwent ETMOWD combined with FROD orbital decompression surgery,which resulted in a decrease in intraocular pressure(IOP)from(19.43±3.9)mmHg preoperatively to(15.05±2.2 mmHg postoperatively(P<0.001).Both horizontal and vertical strabismus increased after surgery.Conclusions Our results demonstrated that,compared with the NOD group,the OD group exhibited increased complexity in strabismus surgery,as evidenced by a higher number of operations,total muscle strips,horizontal muscle strips,and greater migratory effect size of the horizontal muscles.The combination of ETMOWD and FROD effectively reduced exophthalmos,with a more pronounced effect on the medial rectus muscle compared to the vertical muscles.However,the long-term outcomes between the two groups were similar.

Objective:To investigate tetanus antibody levels and distribution characteristics in a healthy population of Henan Province.Methods:A cross-sectional survey was conducted in Henan Province from 2022 to 2023 to investigate the permanent population. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-tetanus toxoid IgG antibody (anti-TT), and the positive rate (≥0.01 IU/ml), protection rate (≥0.1 IU/ml) and concentration differences of tetanus antibodies in different populations were analyzed.Results:The age M ( Q1, Q3) of 5 494 participants was 14 (4, 40) years old, with a minimum age of 8 months and a maximum age of 81 years old. The male-to-female ratio was 1.00∶1.18. The total positive rate, protective rate and mean concentration (MC) [ M ( Q1, Q3)] of Anti-TT were 76.48%, 41.72% and 0.067 (0.010, 0.154) IU/ml, respectively. The positive rates of Anti-TT in individuals aged <3, 3-5, 6-9, and 10-14 were 95.32%, 96.05%, 97.81%, and 93.17%, respectively, but gradually decreased with age ( χ2trend=1 283.02, P<0.001). The antibody protection rate [82.13% (579/705)] and MC [ M ( Q1, Q3) of 0.160 (0.122, 0.259) IU/ml] in the population under 3 years old were relatively high, and both showed a decreasing trend with age (protection rate: χ2trend=1 889.49, P<0.001; MC: t=-54.22, P<0.001). There were significant differences in antibody levels among populations of different ages, regions, occupations, and immunization histories (all P<0.001). Within 13 years after the last dose of TTCV vaccination, the positive rate of Anti-TT was all greater than 90%, but the protection rate and MC continued to decrease with the prolongation of vaccination time (protection rate: χ2trend=160.58, P<0.001; MC: t=-14.93, P<0.001). After the last dose of vaccination, the protection rate and MC [ M ( Q1, Q3)] decreased to 30.43% and 0.055 (0.036, 0.115) IU/ml, respectively, for 10-13 years. The protection rates of Anti-TT for farmers, workers, people aged 60 and above, and women of childbearing age (20-45 years old) were 7.77%, 22.96%, 8.39%, and 12.72%, respectively. Conclusion:The level of tetanus antibodies in infants and young children in Henan Province is relatively high from 2022 to 2023, but it decreases with age and prolonged post-immunization time. There are significant differences in antibody levels among individuals of different ages, regions, occupations, and immunization histories. Occupational high-risk groups such as farmers and workers, elderly people, and women of childbearing age lack sufficient immunization protection.