Objective To explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

Objective To investigate the correlation between serum galectin-3(Gal-3),fibroblast growth factor-21(FGF-21)and the lung function and and the Modified British Medical Research Council dyspnea in-dex(mMRC)score in invalids with chronic obstructive pulmonary disease(COPD).Methods A total of 79 patients with COPD who received treatment in the hospital from April 2021 to April 2023 were selected as the observation group,and 60 healthy individuals in the hospital during the same period were selected as control group.The expressions of Gal-3 and FGF-21 in serum were detected and compared.The first second forced ex-piratory volume(FEV1),FEV1/forced vital capacity(FVC)and mMRC score in two groups were compared,and the correlation between the expression levels of Gal-3 and FGF-21 and FEV1,FEV1/FVC and mMRC score in COPD patients was analyzed.Results The expression levels of serum Gal-3 and FGF-21 in the obser-vation group were higher than those in the control group(P＜0.05).The pulmonary function indexes in ser-um of observation group were higher than those in the control group,while the mMRC score was lower than that in the control group(P＜0.05).The expression levels of Gal-3 and FGF-21 were positively correlated with FEV1 and FEV1/FVC(P＜0.05),was negatively correlated with mMRC score(P＜0.05).Conclusion The expression of serum Gal-3 and FGF-21 in COPD invalids is abnormal,and the expression levels of serum Gal-3 and FGF-21 in COPD patients were correlated with FEV1,FEV1/FVC and mMRC score,which could be used as important reference indicators for diagnosis and disease evaluation of COPD.

Objective To analyze the relationship between neuroticism and gastroesophageal reflux disease (GERD) using the Mendelian randomization (MR) method. Methods Exposure and outcome data were downloaded from the Integrative Epidemiology Unit (IEU) database in August 2023, including summary statistics from genome-wide association studies (GWAS) for neuroticism (n=374 323) and GERD (n=602 604). MR was conducted using the weighted median method, MR-Egger method, inverse variance weighted method, weighted mode method, and simple mode method. The causal relationship between the two was assessed using odds ratio (OR), and sensitivity analyses were performed to ensure the accuracy of the results. Results Neuroticism was associated with an increased risk of GERD [OR=1.229, 95%CI (1.186, 1.274), P<0.001]. Similarly, GERD was associated with an increased risk of neuroticism [OR=1.786, 95%CI (1.623, 1.965), P<0.001]. Conclusion There is a bidirectional causal relationship between neuroticism and gastroesophageal reflux disease.

Objective To identify causal effects and potential mechanisms of oxidative stress (OS)-related genes in lung cancer. Methods OS-related genes were extracted from the GeneCards database. Integration analysis of genome-wide association study (GWAS) data for lung cancer with gene expression and DNA methylation quantitative trait locus (QTL), including eQTL and mQTL in blood was performed using the summary data-based Mendelian randomization (SMR) approach to determine the causal relationship between OS-related genes and lung cancer risk. Colocalization analysis of OS-related gene QTL and lung cancer risk locus was performed to gain insight into the potential regulatory mechanisms of lung cancer risk. Results A total of 1 188 OS-related genes were obtained from the GeneCards database. A potential causal relationship between OS-related genes and lung cancer was identified by SMR analysis. AGER expression level [OR=1.944, 95%CI (1.431, 2.640), P<0.001], and ATF6B expression level [OR=1.508, 95%CI (1.287, 1.767), P<0.001] were associated with lung cancer risk. Meanwhile, ATF6B methylation level was also associated with lung cancer risk. Conclusion OS-related genes are associated with lung cancer, which may be a potential target of anti-cancer drugs.

Objective To investigate the value of gemstone spectral CT multiparameter for risk assessment in acute pulmonary embolism(APE).Methods A total of 83 patients diagnosed with APE were categorized into three groups based on the European Society of Cardiology(ESC)guidelines:high-risk group(n=23),medium-high-risk group(n=29),and medium-low-risk group(n=31).The spectral CT multiparameters for each group were subsequently analyzed and compared.The predictive value of the region of interest perfusion defect iodine group value(ROI vPD),whole lung mean perfusion iodine group value(vMeanIP),and lung perfusion defect volume ratio(rPDvol)in high-risk APE patients were assessed using receiver operating characteristic(ROC)curves.Pearson correlation was employed to analyze the correlation of gemstone spectral CT multiparameter with pulmonary artery obstruction index(PAOI)and right ventricle/left ventricle diameter ratio(rRVD/LVD).Results Whole lung minimum perfusion iodine group value(vMinIP),whole lung maximum perfusion iodine group value(vMaxIP),vMeanIP,rPDvol and right ventricle/left ventricle volume ratio(rRVV/LVV)exhibited significant differences across all groups.The area under the curve(AUC)for ROI vPD,vMeanIP,and rPDvol in high-risk APE patients were 0.792,0.831,and 0.884,respectively.The sensitivity and specificity for ROI vPD(≤0.3),vMeanIP(≤1.1),and rPDvol(≥23.7％)were recorded at 95.7％and 60.0％,78.3％and 75.0％,as well as 91.3％and 75.0％,respectively.Simultaneously,the gemstone spectral CT multiparameter exhibited correlations with PAOI and rRVD/LVD.Conclusion The gemstone spectral CT multiparameter can be utilized to evaluate the severity and progression of patients with APE.

Objective:To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid(99mTc-DTPA)in different brain regions of adult rats after administration through brain extracellular space(ECS)pathway.Methods:After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq(100 μCi)of 99mTc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain,the single photon emission computed tomography/computed tomography(SPECT/CT)for small animals was used for imaging at different time points,and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously.The SD rats were injected with 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo.They were put to death 4 h later.Their blood and urine were collected.The brain,cerebellum,heart,liver,spleen,lung,and kidney were taken and weighed by γ counter to measure its radioactivity.Results:SPECT/CT imaging results showed that after 99mTc-DTPA was administered through brain ECS,the radioactivity was concentrated in the brain,kidney and bladder.The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum,while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum.There was a phenomenon of"con-tralateral cerebellar dominant drainage"in the caudate nucleus.The thalamic area preferentially drained to the ipsilateral cerebellum after administration.Four hours after administration via ECS,high radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.Conclusion:Intracerebral ECS administration is a promising method of administration,but there are significant differences in distribution and clearance in different brain regions.This study further ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Janus Kinase 2/genetics* ; Polysaccharides/administration & dosage* ; Colitis, Ulcerative/chemically induced* ; Mice ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Drug Synergism ; Male ; Hesperidin/administration & dosage* ; Platycodon/chemistry* ; Phosphatidylinositol 3-Kinases/genetics* ; Disease Models, Animal ; RAW 264.7 Cells ; Mice, Inbred C57BL

Objective:To investigate the role of O-GlcNAcylation in the regulation of the stability of receptor for activated C kinase 1(Rack1)during SHH-type medulloblastoma(SHH-MB)initiation.Methods:SHH-MB tumors and adjacent tissues were selected from the clinical tu-mor specimen library of the Department of Pathology at The General Hospital of Western Theater Command.Rack1 expression and O-GlcNAcylation(O-GlcNAc)levels in these tumor tissues were analyzed.The human medulloblastoma cell line Daoy was treated with a glyc-osyltransferase(OGT)inhibitor(OSMI-1)and adeglycosyltransferase(OGA)inhibitor(TM-G),and their impact on tumor cell proliferation was assessed using a Cell Counting Kit-8(CCK-8)and immunofluorescence staining.The O-GlcNAc enzyme labeling system co-immunoprecipita-tion(Co-IP)and Western blot were used to correlate Rack1 protein levels with O-GlcNAc levels.The impact of O-GlcNAcon Rack1 stability was confirmed using cycloheximide(CHX)and ubiquitination modification experiments.In a medulloblastoma mouse model with Rack1 knockdown,tumor cell proliferation was detected using a Cell Counting Kit-8(CCK-8),immunofluorescence staining,and a scratch assay.Xenograft tumors were transplanted into immunodeficient mice and SHH signaling was detected by Western blot in the obtained tissue samples(sh-NC and sh-Rack1)to verify the role of Rack1 protein in SHH-MB.Results:Rack1 and O-GlcNAcylation levels were significantly in-creased in SHH-MB tumor samples,and a negative correlation was observed between Rack1 levels and patient survival rates.Treatment of Daoy cells with OGT and TM-G revealed that O-GlcNAc significantly promotes Daoy cell proliferation,while inhibiting O-GlcNAc impedes tu-mor cell proliferation.Molecular experiments have confirmed that O-GlcNAc modification of Rack1 protein can regulate tumor cell stability,thereby promoting tumor cell proliferation.When Rack1 expression was knocked down in Daoy cells,cell proliferation was significantly re-duced relative to control cells.Accordingly,proliferation was significantly inhibited in tumor tissues with Rack1 protein knockdown in mouse models,suggesting that Rack1 can participate in the initiation of SHH-MB by regulating SHH signaling.Conclusions:O-GlcNAcylation particip-ates in SHH-MB initiation by regulating Rack1 stability.

Objective:To investigate immunological non-responders (INRs) and immunological responders (IRs) during long-term antiretroviral therapy (ART), and study the dynamics of HIV reservoir and α4β7 cells in INRs and IRs and their correlation.Methods:Twenty-six patients with chronic HIV infection who received ART for 5 years were included. They were divided into INRs (CD4 + T cell counts≤350 cells/μl, n=9) and IRs (CD4 + T cell counts≥500 cells/μl, n=17) based on immune reconstitution outcomes. The percentages and numbers of α4β7 cells in both groups at baseline, ART 1, 3, and 5 years were detected by flow cytometry, and the levels of HIV DNA and cell-associated HIV RNA were quantified by real-time fluorescent quantitative PCR during the same periods. HIV viral decay, α4β7 cells dynamics, and their correlations with T cells were compared at baseline, ART 1, 3 and 5 years between the two groups. Results:Over 5 years of ART, INRs exhibited higher HIV reservoir levels compared to IRs, but the decline trend was not slow. The counts of α4β7 cell were lower and the growth trend was slow in INRs ( P<0.05). α4β7 cell counts were strongly positively correlated with CD4 + T cell counts at all timepoints (Year 1: r=0.887; Year 3: r=0.878; Year 5: r=0.887; P all <0.001), while showing significantly negative correlations with activated CD38 + HLA-DR + CD4 + T cells (Year 1: r=-0.619, P=0.001), CD38 + HLA-DR + CD8 + T cells (Year 1: r=-0.517; Year 5: r=-0.532; P all <0.01), and PD-1 + CD4 + T cells (Year 1: r=-0.476, Year 5: r=-0.390, P all <0.05). Conclusions:During long-term ART, INRs maintained higher HIV reservoir and lower α4β7 cell counts compared with IRs, and decreased α4β7 cells may be associated with disease progression.

This study summarizes the disease diagnosis and operation coding for tumor radiotherapy.The designated di-agnosis code is Z51.0,and the operation codes range from 92.2 to 92.4.By analyzing a typical case from a tertiary cancer hospi-tal,the practical application of these codes is elucidated.Furthermore,strategies to improve coding quality are proposed,aiming to improve the accuracy,completeness,and standardization of radiotherapy diagnosis and operation coding.These measures are expected to facilitate standardized and refined management of medical services with radiotherapy.