Objective:To evaluate the diagnostic value of coronary angiography-derived fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) for identifying coronary functional abnormalities.Methods:This diagnostic study enrolled patients with clinically suspected or diagnosed coronary artery disease who underwent coronary angiography at Beijing Anzhen Hospital, TEDA International Cardiovascular Hospital, and Qilu Hospital of Shandong University between December 2021 and June 2022. All enrolled patients successfully underwent invasive wire-based FFR and IMR measurements during angiography. In a core laboratory, FFR and IMR for the target vessels were measured using artificial intelligence technology based on coronary angiographic images. Spearman correlation analysis was used to evaluate the correlation between angiography-derived FFR and wire-based FFR, and between angiography-derived IMR and wire-based IMR. Coronary hemodynamic abnormality was defined as FFR≤0.80; the diagnostic performance of angiography-derived FFR for identifying this abnormality was evaluated. Microcirculatory dysfunction was defined as IMR≥25; the diagnostic performance of angiography-derived IMR for identifying microcirculatory dysfunction was evaluated.Results:A total of 181 patients, aged (60.6±8.8) years, with 62 (34.3%) females, and 181 target vessels were included in the final analysis. Angiography-derived FFR showed a significant positive correlation with wire-based FFR ( r=0.78, P<0.001). For identifying coronary hemodynamic abnormality, angiography-derived FFR showed an accuracy of 89.0%, sensitivity of 88.8%, specificity of 89.1%, positive predictive value (PPV) of 88.8%, negative predictive value (NPV) of 89.1%, and an area under the receiver operating characteristic curve ( AUC) of 0.88. Angiography-derived IMR showed a significant positive correlation with wire-based IMR ( r=0.93, P<0.001). For identifying microcirculatory dysfunction, angiography-derived IMR demonstrated an accuracy of 89.5%, sensitivity of 86.8%, specificity of 90.2%, PPV of 70.2%, NPV of 96.3%, and an AUC of 0.95. Conclusion:Angiography-derived FFR and IMR exhibit strong correlations with their invasive wire-based counterparts and demonstrate high diagnostic value for assessing coronary hemodynamics and coronary microcirculatory function.

Objective:To explore the effect of insulin-like growth factor 2 ( IGF2) mRNA binding protein 2 (IGF2BP2) inhibitor CWI1-2 on migration and invasion of glioma cells SHG-140 and LN229 as well as their resistance to temozolomide (TMZ). Methods:(1) SHG-140 and LN229 glioma cell lines were cultured in vitro; cell counting kit-8 (CCK-8) assay was used to detect the effects of 0.1, 0.2, 0.5, 1.0, 2, and 5 μmol/L CWI1-2 on survival rate of the two cell lines at 24 and 48 hours after treatment, and the best concentration and treatment time of CWI1-2 were screened. SHG-140 and LN229 cells were categorized into control group, 0.5 μmol/L CWI1-2 group, and 1.0 μmol/L CWI1-2 group, respectively, and equal amount of medium, 0.5 μmol/L CWI1-2 and 1.0 μmol/L CWI1-2 were added into the cells for 24 hours; Western blotting and immunofluorescent staining were used to detect the IGF2BP2 protein expression; cell scratch assay and Transwell assay were, respectively, used to detect the cell migration and invasion. (2) CCK-8 assay was employed to detect the effects of 100, 200, 400, 600, 800, and 1000 μmol/L TMZ on survival rate of SHG-140 and LN229 cells at 24 and 48 hours after treatment, and the best concentration and treatment time of TMZ were screened. SHG-140 and LN229 cells were categorized into control group, CWI1-2 group, TMZ group, and TMZ+CWI1-2 group, respectively, and equal amounts of culture medium, 0.5 μmol/L CWI1-2, 200 μmol/L TMZ, and 0.5 μmol/L CWI1-2+200 μmol/L TMZ were added into the 4 groups for 24 hours, respectively; colony formation assay was used to detect the colony formation rate and CCK-8 assay was utilized to determine the proliferation rate. Results:(1) CCK-8 results indicated that, compared with the 0.1 and 0.2 μmol/L CWI1-2 groups, SHG-140 and LN229 cells in the 0.5, 1.0, 2, and 5 μmol/L CWI1-2 groups had significantly lower survival rate at 24 and 48 hours after treatment ( P<0.05); furthermore, the survival rate in the SHG-140 and LN229 cells of the 0.5, 1.0, 2, and 5 μmol/L CWI1-2 groups decreased successively, with statistical differences ( P<0.05); therefore, 0.5 μmol/L and 1 μmol/L CWI1-2 for 24 hours with less effect on survival rate were selected for subsequent experiments. Western blotting results showed that, compared with the control group (1.27±0.05), the SHG-140 cells in 0.5 and 1.0 μmol/L CWI1-2 groups had significantly lower IGF2BP2 protein expression (0.91±0.09, 0.79±0.10; P<0.05); compared with the control group and 0.5 μmol/L CWI1-2 group (0.82±0.09, 0.82±0.04), the LN229 cells in 1.0 μmol/L CWI1-2 group had significantly lower IGF2BP2 protein expression (0.33±0.02, P<0.05). Immunofluorescent staining results showed that, compared with the control group, the 0.5 and 1.0 μmol/L CWI1-2 groups had obviously decreased IGF2BP2 protein immunofluorescent intensity. Cell scratch assay results showed that, compared with the control group, the SHG-140 cells in 0.5 and 1.0 μmol/L CWI1-2 groups had significantly lower migration rate ( P<0.05); the migration rate in LN229 cells of the control group, 0.5 μmol/L CWI1-2 group and 1.0 μmol/L CWI1-2 group decreased successively, with statistical differences ( P<0.05). Transwell assay results showed that the number of transmembrane SHG-140 and LN229 cells in the control group, 0.5 μmol/L CWI1-2 group and 1.0 μmol/L CWI1-2 group decreased successively, with significant differences ( P<0.05). (2) CCK-8 assay results showed that compared with the 100 and 200 μmol/L TMZ groups, SHG-140 and LN229 cells in the 400, 600, 800 and 1000 μmol/L TMZ groups had statistically lower survival rate at 24 and 48 hours after treatment ( P<0.05); therefore, concentration with less effect on cell survival rate (200 μmol/L TMZ) was selected for subsequent experiments. The cell colony formation rate of SHG-140 and LN229 cells in the control group, CWI1-2 group, TMZ group and TMZ+CWI1-2 group decreased successively, with significant differences ( P<0.05). Cell proliferation rate of LN229 cells in the control group, CWI1-2 group, TMZ group and TMZ+CWI1-2 group decreased successively, with significant differences ( P<0.05). Conclusion:CWI1-2 can inhibit the proliferation and invasion of glioma cells, and can also increase the killing effect of TMZ on glioma cells.

Objective:To explore the effect of insulin-like growth factor 2 ( IGF2) mRNA binding protein 2 (IGF2BP2) inhibitor CWI1-2 on migration and invasion of glioma cells SHG-140 and LN229 as well as their resistance to temozolomide (TMZ). Methods:(1) SHG-140 and LN229 glioma cell lines were cultured in vitro; cell counting kit-8 (CCK-8) assay was used to detect the effects of 0.1, 0.2, 0.5, 1.0, 2, and 5 μmol/L CWI1-2 on survival rate of the two cell lines at 24 and 48 hours after treatment, and the best concentration and treatment time of CWI1-2 were screened. SHG-140 and LN229 cells were categorized into control group, 0.5 μmol/L CWI1-2 group, and 1.0 μmol/L CWI1-2 group, respectively, and equal amount of medium, 0.5 μmol/L CWI1-2 and 1.0 μmol/L CWI1-2 were added into the cells for 24 hours; Western blotting and immunofluorescent staining were used to detect the IGF2BP2 protein expression; cell scratch assay and Transwell assay were, respectively, used to detect the cell migration and invasion. (2) CCK-8 assay was employed to detect the effects of 100, 200, 400, 600, 800, and 1000 μmol/L TMZ on survival rate of SHG-140 and LN229 cells at 24 and 48 hours after treatment, and the best concentration and treatment time of TMZ were screened. SHG-140 and LN229 cells were categorized into control group, CWI1-2 group, TMZ group, and TMZ+CWI1-2 group, respectively, and equal amounts of culture medium, 0.5 μmol/L CWI1-2, 200 μmol/L TMZ, and 0.5 μmol/L CWI1-2+200 μmol/L TMZ were added into the 4 groups for 24 hours, respectively; colony formation assay was used to detect the colony formation rate and CCK-8 assay was utilized to determine the proliferation rate. Results:(1) CCK-8 results indicated that, compared with the 0.1 and 0.2 μmol/L CWI1-2 groups, SHG-140 and LN229 cells in the 0.5, 1.0, 2, and 5 μmol/L CWI1-2 groups had significantly lower survival rate at 24 and 48 hours after treatment ( P<0.05); furthermore, the survival rate in the SHG-140 and LN229 cells of the 0.5, 1.0, 2, and 5 μmol/L CWI1-2 groups decreased successively, with statistical differences ( P<0.05); therefore, 0.5 μmol/L and 1 μmol/L CWI1-2 for 24 hours with less effect on survival rate were selected for subsequent experiments. Western blotting results showed that, compared with the control group (1.27±0.05), the SHG-140 cells in 0.5 and 1.0 μmol/L CWI1-2 groups had significantly lower IGF2BP2 protein expression (0.91±0.09, 0.79±0.10; P<0.05); compared with the control group and 0.5 μmol/L CWI1-2 group (0.82±0.09, 0.82±0.04), the LN229 cells in 1.0 μmol/L CWI1-2 group had significantly lower IGF2BP2 protein expression (0.33±0.02, P<0.05). Immunofluorescent staining results showed that, compared with the control group, the 0.5 and 1.0 μmol/L CWI1-2 groups had obviously decreased IGF2BP2 protein immunofluorescent intensity. Cell scratch assay results showed that, compared with the control group, the SHG-140 cells in 0.5 and 1.0 μmol/L CWI1-2 groups had significantly lower migration rate ( P<0.05); the migration rate in LN229 cells of the control group, 0.5 μmol/L CWI1-2 group and 1.0 μmol/L CWI1-2 group decreased successively, with statistical differences ( P<0.05). Transwell assay results showed that the number of transmembrane SHG-140 and LN229 cells in the control group, 0.5 μmol/L CWI1-2 group and 1.0 μmol/L CWI1-2 group decreased successively, with significant differences ( P<0.05). (2) CCK-8 assay results showed that compared with the 100 and 200 μmol/L TMZ groups, SHG-140 and LN229 cells in the 400, 600, 800 and 1000 μmol/L TMZ groups had statistically lower survival rate at 24 and 48 hours after treatment ( P<0.05); therefore, concentration with less effect on cell survival rate (200 μmol/L TMZ) was selected for subsequent experiments. The cell colony formation rate of SHG-140 and LN229 cells in the control group, CWI1-2 group, TMZ group and TMZ+CWI1-2 group decreased successively, with significant differences ( P<0.05). Cell proliferation rate of LN229 cells in the control group, CWI1-2 group, TMZ group and TMZ+CWI1-2 group decreased successively, with significant differences ( P<0.05). Conclusion:CWI1-2 can inhibit the proliferation and invasion of glioma cells, and can also increase the killing effect of TMZ on glioma cells.

Objective:To evaluate the diagnostic value of coronary angiography-derived fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) for identifying coronary functional abnormalities.Methods:This diagnostic study enrolled patients with clinically suspected or diagnosed coronary artery disease who underwent coronary angiography at Beijing Anzhen Hospital, TEDA International Cardiovascular Hospital, and Qilu Hospital of Shandong University between December 2021 and June 2022. All enrolled patients successfully underwent invasive wire-based FFR and IMR measurements during angiography. In a core laboratory, FFR and IMR for the target vessels were measured using artificial intelligence technology based on coronary angiographic images. Spearman correlation analysis was used to evaluate the correlation between angiography-derived FFR and wire-based FFR, and between angiography-derived IMR and wire-based IMR. Coronary hemodynamic abnormality was defined as FFR≤0.80; the diagnostic performance of angiography-derived FFR for identifying this abnormality was evaluated. Microcirculatory dysfunction was defined as IMR≥25; the diagnostic performance of angiography-derived IMR for identifying microcirculatory dysfunction was evaluated.Results:A total of 181 patients, aged (60.6±8.8) years, with 62 (34.3%) females, and 181 target vessels were included in the final analysis. Angiography-derived FFR showed a significant positive correlation with wire-based FFR ( r=0.78, P<0.001). For identifying coronary hemodynamic abnormality, angiography-derived FFR showed an accuracy of 89.0%, sensitivity of 88.8%, specificity of 89.1%, positive predictive value (PPV) of 88.8%, negative predictive value (NPV) of 89.1%, and an area under the receiver operating characteristic curve ( AUC) of 0.88. Angiography-derived IMR showed a significant positive correlation with wire-based IMR ( r=0.93, P<0.001). For identifying microcirculatory dysfunction, angiography-derived IMR demonstrated an accuracy of 89.5%, sensitivity of 86.8%, specificity of 90.2%, PPV of 70.2%, NPV of 96.3%, and an AUC of 0.95. Conclusion:Angiography-derived FFR and IMR exhibit strong correlations with their invasive wire-based counterparts and demonstrate high diagnostic value for assessing coronary hemodynamics and coronary microcirculatory function.

Objective To investigate the regulating mechanism of Notch1 signaling pathway on the invasion and migration ofglioma initiating cells (GICs).Methods (1) Box-plotting was conducted to analyze the mRNA expression of Notch1 in normal brain tissue and glioblastoma tissue using Bredel Brain,Sun Brain and TCGA databases;Kaplan-Meier survival analysis was conducted to analyze the association between the prognosis of glioma patients with the expression of Hes1 in TCGA database;Heatmap was conducted to analyze the expression of Notch1 and CXCR4 in GICs and common cell line in GEO database.(2) Magnetic activated cell sorting was adopted to establish cell lines of U87 GICs and U251 GICs;immunofluorescence staining was used to detect expression of CXCR4 and Notch1.After the cell lines of U87 GICs and U251 GICs were divided into DMSO,shNC,MK0752 and shNotchl groups,the shNotch1 and shNC groups were transfected respectively with recombinant lentivirus of Notch1-shRNA and its control sequence while the MK0752 and DMSO groups were added respectively with MK-0752 of 80 nmol/mL and the same amount of DMSO.The protein expression of Notch1,CXCR4 and p-mTOR was detected by Westem blotting in the 4 groups.The capabilities of invasion and migration of the GICs were detected by Transwell assay in the shNotch1 and shNC groups.Results (1) The box-plotting showed the mRNA expression of Notch 1 in the glioblastoma tissue was significantly higher than in the normal brain tissue (P＜0.05).The Kaplan-Meier survival analysis showed that the life span ofglioma patients with high expression of Hes1 was significantly shorter than that of those with low expression of Hes1 (P＜0.05).Heatmaps showed that the expression levels of Notch1 and CXCR4 in GICs were higher than in the common cell line.(2) The immunofluorescence staining showed that Notch1 and CXCR4 were highly expressed and colocalized in cell lines of U87 GICs and U251 GICs.The Western blotting showed that the protein expression of Notch1,CXCR4 and p-mTOR in the cell lines of U87GICs and U251 GICs in the MK0752 and shNotch1 groups was lower than that in the DMSO and shNC groups.Transwell assay showed that the penetrating-membrane cells per visual field in the shNotch1group were significantly fewer than those in the shNC group (P＜0.05).Conclusion Notch1 signaling pathway can promote invasion and migration of GICs through regulating CXCR4 expression.

Tumor immunotherapy refers to the application of immunological principles and methods to stimulate and enhance the body's antitumor immune response as well as assist the immune system to kill tumors and inhibit tumor growth.These methods in-volve injecting immune cells and effector molecules into the host.Immunotherapy,especially immunoprecipitation treatment,has ex-erted a strong antitumor effect on melanoma,renal cell carcinoma,non-small cell lung cancer,and hematological malignancies.This method has also received widespread attention.However,in malignant glioma,immunotherapy is still in its infancy.Numerous clinical trials have shown that immunotherapy for glioma is feasible and safe.This paper reviews the latest advances in immunization strate-gies,such as immunological checkpoints,adoptive immunotherapy,and tumor vaccines,to provide new ideas for glioma treatment.

Objective To study the expression level and clinical significance of Galectin-3 and miRNA-21 in non-small-cell lung carcinoma(NSCLC).Methods One hundred and fifty patients with NSCLC were chosen as cancer group,and 1 50 patients with benign pulmonary diseases were chosen as control group.The expression level of Galectin-3 and that of miRNA-21 between two groups were compared,and the relevance between expression level of Galectin-3 and that of miRNA-21 and clinical feature were analysed.Results In cancer group,the expression level of Galectin-3 was 6.75±2.38,and that of control group was 1.12 ±0.29;the expression level of miRNA-21 was 5.91 ± 1.59,and that of control group was 0.97 ± 0.1 7,and the difference between two groups had statistical significance(P <0.05 ).The relevance between expression level of Galectin-3 and stage,differentiation,lym-phatic metastasis,diameter of carcinoma and PFS,OS of patients had statistical significance(P <0.05).The relevance between ex-pression level of miRNA-21 and stage,differentiation,diameter of carcinoma and PFS,OS of patients had statistical significance(P <0.05).In the diagnosis of NSCLC,the sensitivity of the expression level of Galectin-3 was 90.20%,and its specificity was 70.69%, while the sensitivity of expression level of miRNA-21 was 88.24% and its specificity was 69.97%.The difference between the di-agnostic value of Galectin-3 and that of miRNA-21 had no statistical significance(P >0.05 ).Conclusion The expression level of Galectin-3 and that of miRNA-21 can be applied in the diagnosis and prognosis of non-small-cell lung carcinoma.

OBJECTIVE To investigate pathogenetic condition and fungal detection on evaluating acute exacerbation of COPD(AECOPD),and the relation of the severity and risk of death during hospital stay.METHODS Samples of sputum,blood and pleural effusion from patients with bronchopulmonary candidiasis in our respiratory department were collected since from Jul 2007 to Jun 2007.All of patients carried out APACHEⅡ integrating,according to the results of APACHEⅡsubset to Knaus equations to calculate the risk of death during hospital stay.RESULTS Twenty-two strains of fungi were isolated from 119 patients(18.4%).Blood gas analysis of severe COPD patients indicated a respiratory failure tendency,the fungal detection rate was higher than that of mild or median COPD patients.The higher of APACHEⅡ accumulated points,the higher of fungal detection rate,and the higher of risk of death.CONCLUSIONS The most organisms in respiratory tract infection are bacterium.With number of admission times in hospital and severity of pathogenetic condition increased are,the opportunity of fungal infection is raised.Furthermore,the fungal infection associatively with exacerbation.Fungi become the ascendant causative organisms inducing the decrese in pulmonary function and severity of patients,we should think about of it when the therapeutic efficacy is worse.

AIM: To investigate the effects of oral administration of Astragalus membranceus, mung bean and arsenolite on the toxic of the arsenolite induced rats and the possible mechanisms with metallothionein (MT). METHODS: All the rats were oral administration with arsenolite. The Astragalus membranceus and mung bean were compared with the cadmium chloride which induced MT synthesis. The contents of MT were determined by cadmium saturation method, the liver mRNA levels for MT 1, MT 2 were detected by RT PCR. The protective effects of renal and liver were observed by testing alanine aminotransferase (ALT), blood urea nitrogen (BUN) and serum creatinine (SCR). RESULTS: The contents of MT were accorded with the mRNA expression of MT 1, MT 2. Arsenolite, Astragalus membranceus and mung bean could induce the synthesis of MT, but the contents of MT which arsenolite induced were trace. The contents of MT significantly increased after oral administration of Astragalus membranceus and mung bean, especially in the Astragalus membranceus group (P