Objective:To assess a value of dual energy index(DEI)and effective atomic number(Zeff)of dual-energy computed tomography(DECT)combined with slope of energy spectrum curve in identifying the component of urinary tract stones.Methods:The clinical and DECT imaging data of 111 patients with urinary tract stones who admitted to Nantong Haimen People's Hospital from October 2019 to October 2022 were selected,and the diameters of the urinary tract stones of all patients were<5 mm.The components of outside body stones of all patients were analyzed by infrared spectrum.The accuracy,sensitivity and specificity of the DEI,Zeff,slope of energy spectrum curve and the combination of the them were respectively calculated in identifying the components of urinary tract stones.Results:In 111 patients,the patients with calcium oxalate stones were 75(67.57%),and ones with hydroxyapatite were 15 cases(13.51%),and ones with uric acid stones were 21 cases(18.92%),and there were no other type of stone included cysteine.The differences of CT values(F=487.691,P<0.001),DEI values(F=395.553,P<0.001),Zeff values(F=818.689,P<0.001)and the slopes of energy spectrum curves(H=19.615,P<0.001)were statistically significant among the three types of stones.The overall accuracies of DEI,Zeff and slope of energy spectrum curve were 87.39%(97/111),84.68%%(94/111)and 81.98%(91/111)in identifying the components of urinary tract stone.The range of diagnostic accuracies of DEI,Zeff and the slope of energy spectrum curve was between 80%and 100%for calcium oxalate stones,hydroxyapatite and uric acid stones.The overall accuracy of DEI,Zeff combined with slope of energy spectrum curve was 94.59%(105/111)in identifying the components of urinary tract stones.The diagnostic accuracies of DEI,Zeff combined with slope of energy spectrum curve were respectively 94.59%,94.59 and 100%for calcium oxalate stones,hydroxyapatite and uric acid stones.Conclusion:Compared with the single indicator of DECT,the DEI and Zeff combined with the slope of the energy spectrum curve showed better diagnostic accuracy in identifying the components urinary track stones.

Objective To evaluate the diagnostic efficacy of diffusion kurtosis imaging(DKI)histograms in predicting isocitrate dehydrogenase(IDH)mutations and grade in gliomas.Methods Sixty-four patients with pathologically confirmed gliomas with IDH gene phenotype results were included,all of whom underwent DKI,and mean kurtosis(MK)and mean diffusivity(MD)maps were generated.The whole tumor was outlined on the MK and MD maps in all slices,and histograms of the full tumor volume MK and MD were calculated.The histogram parameters between IDH mutant and wild type gliomas,and the MK and MD histogram parameters between high grade glioma(HGG,grade 3-4)and low grade glioma(LGG,grade 2)were compared.Receiver operating characteristic(ROC)curve was used to assess the predictive efficacy in determining IDH gene phenotype and grade of gliomas in statistically different parameters.Results Of the 64 gliomas,39 were IDH mutant and 25 were IDH wild type.The MKmax and MK90th in IDH mutant gliomas were lower than that in IDH wild type,while the MDmin,MD10th and MD30th were greater than that in IDH wild type.The area under the curve(AUC)of MKmax was 0.883 in differentiation of the IDH mutant and the IDH wild type,and when the MKmax was greater than 0.745,its sensitivity and specificity in predicting IDH mutations were 81.8％and 82.4％,respectively.There were 28 cases of LGG and 36 cases of HGG;the MKmax,MK70th,and MK90th of HGG were greater than that of LGG,while the MDmin and MD10th were lower than that of LGG,in which the MD10th had an AUC of 0.886 in differentiation of HGG and LGG,when MD10th was greater than 1.075 × 10-3 mm2/s,its sensitivity and specificity in predicting HGG were 85.7％and 86.1％,respectively.Conclusion The MKmax in the DKI histogram has the highest predictive efficacy in the IDH phenotype,while the MD10th has the best diagnostic value for glioma grade.

Objective·To investigate the effect of ceria nanoparticles-polyethylene glycol(CeNP-PEG)on scavenging reactive oxygen species(ROS)and alleviating disease activity in dextran sulphate sodium(DSS)-induced colitis mice.Methods·CeNP was synthesized with the hydrates of cerium acetate,oleamine,and xylene,which was modified with polyethylene glycol-stearyl phosphatidylethanolamine(mPEG-DPSE)to obtain CeNP-PEG.Then CeNP-PEG was purified.The particle size and zeta potential of CeNP-PEG were measured by using transmission electron microscopy(TEM)and dynamic light scattering(DLS).Mouse macrophages(Raw264.7)were cultured in vitro and induced to a pro-inflammatory phenotype(M1 phenotype).M1 macrophages were treated with 0.5 μg/mL and 1.0 μg/mL CeNP-PEG,respectively,and then Western blotting was used to detect the expression changes of the proteins related with nuclear factor-κB(NF-κB)signaling pathway.DSS-induced colitis mice models were constructed,and CeNP-PEG(1.0 mg/mL)was intravenously administrated for 3 times via tail vein during the modeling period.Meanwhile,the body weight,fecal characteristics,and frequency of rectal bleeding in mice were monitored in the normal control group(Normal group),the model group(DSS group),and the CeNP-PEG treatment group.The disease activity index(DAI)was calculated to evaluate the intestinal inflammation.The level of ROS in mouse intestinal tissues was detected by dihydroethidine(DHE)staining and the mRNA expression levels of inflammatory cytokines interferon-γ(Ifn-γ),interleukin-6(Il-6),Il-1β and tumor necrosis factor-α(Tnf-α)were detected by real-time quantitative PCR(RT-qPCR).Results·The hydrated particle size of synthesized CeNP-PEG was(6.96±0.27)nm,and the average zeta potential was(-6.02±1.31)mV.Western blotting results showed that the expression of p-P65 increased in the pro-inflammatory macrophages compared with the control group.The expression of NF-κB inhibitor-α(IκB-α)decreased,and their expressions tended to recover after the intervention of different concentrations of CeNP-PEG.In the DSS-induced colitis models,mice in the CeNP-PEG treatment group lost less weight than those in the DSS group(P= 0.000)and had lower DAI scores(P=0.000).The RT-qPCR results of intestinal tissues showed that the mRNA levels of Ifn-γ,Il-1β,Il-6 and Tnf-α in the DSS group were significantly up-regulated compared with those in the Normal group(P=0.000),and all of them significantly decreased in the CeNP-PEG treatment group.The results of DHE staining showed that the fluorescence intensity of intestinal tissues in the DSS group was significantly enhanced than that in the Normal group,and the fluorescence intensity decreased in the CeNP-PEG treatment group.Conclusion·CeNP-PEG can inhibit the expression of intestinal inflammatory factors and the activation of NF-κB-related inflammatory pathway of pro-inflammatory macrophages,eliminate intestinal ROS,improve the intestinal inflammatory microenvironment,and alleviate the disease activity of DSS-induced colitis in mice.

Objective To summarize and analyze the application of regional citrate anticoagulation (RCA) in patients undergoing continuous renal replacement therapy (CRRT) using a scoping review methodology. Methods Following the scoping review methodology, a systematic search was conducted in domestic and international databases, including CNKI, Wanfang Data, Cochrane Library, PubMed, and Embase for literature related to RCA in CRRT patients. The search was limited from the inception of the databases to August 10, 2023. Included studies were screened, summarized, and analyzed. Results A total of 19 articles were included in this study, comprising 8 randomized controlled trials, 8 cohort studies, 2 case-control studies, and 1 cross-sectional survey. Anticoagulation methods for CRRT primarily included unfractionated heparin, low-molecular-weight heparin, thrombin inhibitors, nafamostat, and RCA. Compared to other anticoagulation methods, RCA exhibited advantages in lower bleeding risk and longer filter lifespan. Calcium ion monitoring during RCA application predominantly relies on the empirical trial-and-error approach. Major complications associated with RCA include citrate accumulation, acid-base imbalance, and ion metabolic disorders. For patients with high bleeding risk, hypercalcemia, and sepsis, RCA may confer greater benefits during CRRT. Conclusion RCA has gradually emerged as a preferred anticoagulation method for CRRT patients, offering advantages in extending filter lifespan and reducing bleeding risk. Future research should focus on calcium ion monitoring during RCA, enhancing safety and efficacy through targeted infusion systems, and further exploring the immunomodulatory effects of RCA and its mechanisms related to high inflammatory factor clearance rates.

BACKGROUND: China bears the biggest atrial fibrillation (AF) burden in the world. However, little is known about the incidence and predictors of AF. This study aimed to investigate the current incidence of AF and its electrocardiographic (ECG) predictors in general community individuals aged over 60 years in China. METHODS: This was a prospective cohort study, recruiting subjects who were aged over 60 years and underwent annual health checkups from April to July 2015 in four community health centers in Songjiang District, Shanghai, China. The subjects were then followed up from 2015 to 2019 annually. Data on sociodemographic characteristics, medical history, and the resting 12-lead ECG were collected. Kaplan-Meier curve was used for showing the trends in AF incidence and calculating the predictors of AF. Associations of ECG abnormalities and AF incidence were examined using Cox proportional hazard models. RESULTS: This study recruited 18,738 subjects, and 351 (1.87%) developed AF. The overall incidence rate of AF was 5.2/1000 person-years during an observation period of 67,704 person-years. Multivariable Cox regression analysis indicated age (hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.06-1.09; P < 0.001), male (HR, 1.30; 95% CI: 1.05-1.62; P = 0.018), a history of hypertension (HR, 1.55; 95% CI: 1.23-1.95; P < 0.001), a history of cardiac diseases (HR, 3.23; 95% CI: 2.34-4.45; P < 0.001), atrial premature complex (APC) (HR, 2.82; 95% CI: 2.17-3.68; P < 0.001), atrial flutter (HR, 18.68; 95% CI: 7.37-47.31; P < 0.001), junctional premature complex (JPC) (HR, 3.57; 95% CI: 1.59-8.02; P = 0.002), junctional rhythm (HR, 18.24; 95% CI: 5.83-57.07; P < 0.001), ventricular premature complex (VPC) (HR, 1.76; 95% CI: 1.13-2.75, P = 0.012), short PR interval (HR, 5.49; 95% CI: 1.36-22.19; P = 0.017), right atrial enlargement (HR, 6.22; 95% CI: 1.54-25.14; P = 0.010), and pacing rhythm (HR, 3.99; 95% CI: 1.57-10.14; P = 0.004) were independently associated with the incidence of AF. CONCLUSIONS The present incidence of AF was 5.2/1000 person-years in the studied population aged over 60 years in China. Among various ECG abnormalities, only APC, atrial flutter, JPC, junctional rhythm, short PR interval, VPC, right atrial enlargement, and pacing rhythm were independently associated with AF incidence.
Humans ; Male ; Middle Aged ; Aged ; Atrial Fibrillation/epidemiology* ; Prospective Studies ; Incidence ; Atrial Flutter/complications* ; Risk Factors ; China/epidemiology* ; Electrocardiography

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

BACKGROUND: Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness. This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness. METHODS: A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders (IRs) (CD4 + T-cell count >500) and immunological non-responders (INRs) (CD4 + T-cell count <300) was conducted. The transcriptomic profiles were used to identify distinct cell subpopulations, marker genes, and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness. RESULTS: Among the cellular subpopulations analyzed, the ratios of monocytes, CD16 + monocytes, and exhausted B cells demonstrated the most substantial differences between INRs and IRs, with fold changes of 39.79, 11.08, and 2.71, respectively. In contrast, the CD4 + T cell ratio was significantly decreased (0.39-fold change) in INRs compared with that in IRs. Similarly, the ratios of natural killer cells and terminal effector CD8 + T cells were also lower (0.37-fold and 0.27-fold, respectively) in the INRs group. In addition to several well-characterized immune cell-specific markers, we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus (HIV) replication. Notably, ISG15 , IFITM3 , PLSCR1 , HLA-DQB1 , CCL3L1 , and DDX5 , which have been demonstrated to influence HIV replication through their interaction with viral proteins, emerged as significant monocyte marker genes. Furthermore, the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication. CONCLUSIONS We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs. Host genes associated with HIV replication were identified as markers of, and were found to be differentially expressed in, different types of immune cells.
Humans ; Acquired Immunodeficiency Syndrome ; Transcriptome/genetics* ; HIV ; HIV Infections/genetics* ; Leukocytes, Mononuclear/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; Virus Replication ; Membrane Proteins/metabolism* ; RNA-Binding Proteins/metabolism*

Objective:To evaluate the effect of gabapentin on myocardial ischemia-reperfusion injury and its mechanism.Methods:Sixty male clean SD rats, aged 10 weeks and weighing 250 g~300 g, were divided into 5 groups ( n=12) with 12 rats in each group by random number table method: Sham group, myocardial ischemia reperfusion group (group I/R), gabapentin group (group Gap), LY294002 group (group LY) and gabapentin +LY294002 group (group Gap +LY). The model of myocardial ischemia reperfusion injury was established by ligation of the left anterior descending coronary artery for 30 min and reperfusion for 120 min. Heart rate (HR), mean arterial pressure (MAP) and the rate pressure product (RPP) were recorded at baseline before ischemia (T 0) for 30 min (T 1) and reperfusion for 120 min (T 2) to evaluate hemodynamic changes during ischemia and reperfusion; The frequency of PVCs and VT/VF were recorded to evaluate the occurrence of arrhythmias during ischemia/reperfusion. TTC staining was used to detect myocardial infarction area. And the protein expression levels of PI3K and Akt in myocardial tissue were detected by Western blotting. Results:Compared with group I/R, the myocardial infarction area, PVCs and VT/VF times, and the protein expression levels of PI3K and p-Akt were significantly increased in group Gap ( P<0.05). Compared with group Gap, the area of myocardial infarction, the number of PVCs and VT/VF, and the protein expression of PI3K and p-Akt were significantly decreased in the group Gap +LY ( P<0.05). Conclusions:Gabapentin can alleviate myocardial ischemia-reperfusion injury, and its mechanism is related to the activation of PI3K-AKT signaling pathway.

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3