Model incorporating multiple diffusion MRI features: development and validation of a radiomics-based model to predict adult-type diffuse gliomas grade.

OBJECTIVES: To develop and validate a radiomics-based model (ADGGIP) for predicting adult-type diffuse gliomas (ADG) grade by combining multiple diffusion modalities and clinical and imaging morphologic features. METHODS: In this prospective study, we recruited 103 participants diagnosed with ADG and collected their preoperative conventional MRI and multiple diffusion imaging (diffusion tensor imaging, diffusion kurtosis imaging, neurite orientation dispersion and density imaging, and mean apparent propagator diffusion-MRI) data in our hospital, as well as clinical information. Radiomic features of the diffusion images and clinical information and morphological data from the radiological reports were extracted, and multiple pipelines were used to construct the optimal model. Model validation was performed through a time-independent validation cohort. ROC curves were used to evaluate model performance. The clinical benefit was determined by decision curve analysis. RESULTS: From June 2018 to May 2021, 72 participants were recruited for the training cohort. Between June 2021 and February 2022, 31 participants were enrolled in the prospective validation cohort. In the training cohort (AUC 0.958), internal validation cohort (0.942), and prospective validation cohort (0.880), ADGGIP had good accuracy in predicting ADG grade. ADGGIP was also significantly better than the single-modality prediction model (AUC 0.860) and clinical imaging morphology model (0.841) (all p < .01) in the prospective validation cohort. When the threshold probability was greater than 5%, ADGGIP provided the greatest net benefit. CONCLUSION: ADGGIP, which is based on advanced diffusion modalities, can predict the grade of ADG with high accuracy and robustness and can help improve clinical decision-making. CLINICAL RELEVANCE STATEMENT: Integrated multi-modal predictive modeling is beneficial for early detection and treatment planning of adult-type diffuse gliomas, as well as for investigating the genuine clinical significance of biomarkers. KEY POINTS: • Integrated model exhibits the highest performance and stability. • When the threshold is greater than 5%, the integrated model has the greatest net benefit. • The advanced diffusion models do not demonstrate better performance than the simple technology.

Applying MAP-MRI to Identify the WHO Grade and Main Genetic Features of Adult-type Diffuse Gliomas: A Comparison of Three Diffusion-weighted MRI Models.

RATIONALE AND OBJECTIVES: Currently, there is no noninvasive method to effectively judge the genotype of diffuse gliomas. We explored the association between mean apparent propagator-MRI (MAP-MRI) and WHO grade 2/3, IDH 1/2 mutations, and chromosome 1p/19q combined deletion genotypes in adult-type diffuse gliomas and compared it with the diagnostic efficiency of diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI). MATERIALS AND METHODS: We prospectively recruited 67 participantshistopathologically diagnosed with adult-type diffuse gliomas. Routine MRI, DKI, and DSI were performed before surgery. The extreme and average partial diffusion indexes of solid tumors were measured. A comprehensive assessment of statistically significant diffusion parameters was performed after Bonferroni correction, including ROC curves, correct classification percentage (CCP), integrated discrimination improvement (IDI), net reclassification improvement (NRI), and k-fold cross validation. RESULTS: For differentiating WHO grade 2/3, q-space inverse variance (QIV), mean kurtosis (MK), non-Gaussianity (NG), and return to the origin probability (RTOP) were different (p' < .05), with the mean QIV exhibiting the best diagnostic efficacy and stability (AUC = 0.973, CCP = 0.906). We observed significant differences in mean diffusivity (MD), mean square displacement, QIV, MK, and RTOP between the IDH wild-type and IDH mutant groups (p' < .001) (AUC, 0.806-0.978) and MAP-MRI showed a higher IDI than DTI and DKI (0.094-0.435, NRI > 0, respectively). For the chromosome 1p/19q combined deletion, the minimum QIV was different between the overall (p' < .05) and no significant differences  in MD and MK was observed. CONCLUSION: MAP-MRI effectively predicts the WHO grade 2/3, IDH 1/2 mutations, and chromosome 1p/19q combined deletion in adult-type diffuse gliomas, and it may perform better than DTI and DKT.

LASS2 overexpression enhances early apoptosis of lung cancer cells through the caspase­dependent pathway.

In a previous study by the authors, the longevity assurance homolog 2 (LASS2) gene was determined to inhibit activity of vacuolar H+­ATPase (V­ATPase) by combining with the C subunit (ATP6L) of V­ATPase. However, the influence of LASS2 overexpression and silencing on apoptosis of human lung cancer cells 95D or 95C remains unclear. Thus, the effect of LASS2 on apoptosis and its potential mechanisms were investigated in 95D and 95C cells. Using the lentiviral transfection method, lentiviral vectors of LASS2 overexpression and silencing were transfected into 95D and 95C cells, respectively. The apoptotic ability of tumor cells was observed by flow cytometry. The expression levels of LASS2, Bcl­2, Bax, cytochrome c, caspase­9, and caspase­3 were detected by western blotting. CCK­8 assay was used to detect the growth ability of tumor cells in vitro. Flow cytometric analysis revealed that LASS2 overexpression could promote the early apoptosis of lung cancer cells 95D. CCK­8 assay demonstrated that LASS2 overexpression inhibited the proliferation of 95D cells. Additionally, LASS2 overexpression decreased the expression of Bcl­2, induced the release of cytochrome c from mitochondria, and promoted the activation of caspase­9 and caspase­3. There was a significant difference in the expression of Bcl­2, cytochrome c, caspase­9 and caspase­3 in the LASS2­overexpression group compared with the normal and negative control groups. Alternatively, the aforementioned experiments in lung cancer cells 95C following LASS2 silencing produced the opposite effects. LASS2 may induce early apoptosis of lung cancer cells by influencing the caspase­dependent mitochondrial pathway.

Primary application of mean apparent propagator-MRI diffusion model in the grading of diffuse glioma.

PURPOSE: To evaluate the diagnostic -->performance of mean apparent propagator-magnetic resonance imaging (MAP-MRI) in distinguishing the grades of diffuse gliomas. METHOD: Thirty-six patients with pathologically confirmed diffuse gliomas were enrolled in this study. MAP-MRI parameters were measured in the parenchymal area of the tumour: non-Gaussianity (NG), non-Gaussianity axial (NGAx), non-Gaussianity vertical (NGRad), Q-space inverse variance (QIV), return to the origin probability (RTOP), return to the axis probability (RTAP), return to the plane probability (RTPP), and mean square displacement (MSD). Differences in the parameters between any two grades were compared, the characteristics of the parameters for different diffuse glioma grades were analysed, and receiver operating characteristic (ROC) curves were plotted to analyse the diagnostic value of each parameter. RESULTS: Compared with grade III gliomas, grade II gliomas had lower NG, NGAx and NGRad values. NG, NGAx and NGRad had great area under the ROC curve (AUC) values (0.823, 0.835, and 0.838, P < 0.05). Compared with those of grade IV glioma, the NG, NGAx, NGRad, RTAP and RTOP values for grade II glioma were lower, the QIV values were higher (all P < 0.05). NG, NGAx, NGRad, RTAP, RTOP and QIV had great area under the ROC curve (AUC) values (0.923, 0.929, 0.923,0.793,0.822, and 0.769, P < 0.05). CONCLUSIONS: Quantitative MAP-MRI parameters can distinguish grade II and III and grade II and IV gliomas before surgery but not grade III and IV gliomas. Thus, these parameters have clinical guiding value in the noninvasive preoperative evaluation of tumour pathological grading.

Clinical efficacy of DC-CIK combined with sorafenib in the treatment of advanced hepatocellular carcinoma.

PURPOSE: To explore the therapeutic efficacy and safety of the combination treatment of dendritic cells and cytokine-induced killers (DC-CIK) and sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients diagnosed with advanced HCC and treated with DC-CIK and/or sorafenib in the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University from January 2015 to January 2016 were retrospectively analyzed. HCC patients were divided into (A): control group (oral administration of sorafenib) and (B): observation group (oral administration of sorafenib combined with DC-CIK). Patients were followed up every 4-8 weeks. Overall survival and adverse events of each patient were recorded. Therapeutic efficacy was evaluated using the modified RECIST criteria. RESULTS: After treatment, ALT and TBIL were remarkably elevated in the control group and decreased in the observation group. No significant change in AFP level was seen in the control group after treatment, whereas it was remarkably decreased in the observation group. The efficacy rate was 16.7% and 51.4% in the control and observation group, respectively. Clinical benefit rate (CBR) was 41.9% and 88.6% in the control group and observation group, respectively. The median survival time of the control and observation group was 13.8 and 18.6 months, respectively. In the observation group there was a significant difference in the survival time between patients with Child-Pugh A and Child-Pugh B, respectively. CONCLUSIONS: DC-CIK combined with sorafenib could improve the tumor response rate and prolong overall survival of advanced HCC without increasing the incidence of adverse events. HCC patients achieve a more stable disease condition and longer overall survival with DC-CIK combined with sorafenib than those with individual sorafenib treatment.

Reduction of graphene oxide quantum dots to enhance the yield of reactive oxygen species for photodynamic therapy.

The production of reactive oxygen species (ROS) from graphene oxide quantum dots (GOQDs) and chemically reduced GOQDs (rGOQDs) was studied. This shows that GOQDs and rGOQDs produce ROS including singlet oxygen (1O2), hydrogen peroxide (H2O2) and superoxide anion (O2˙-). Interestingly, the rGOQDs exhibit a higher yield of ROS under white light in comparison with GOQDs, indicating the enhanced photodynamic effect through chemical reduction of GOQDs. Studies on the relation between their structures and the yield of ROS demonstrate that the reduction of GOQDs with hydrazine hydrate decreases the band gap and valence band of GOQDs and results in more electron-hole pairs, which leads to an improvement in the yield of ROS from rGOQDs. This research explores the specific species of ROS generated from GOQDs, and provides an efficient avenue to improve the yield of ROS through surface modification of GOQDs.

[Protective effects of acidic fibroblast growth factor on intestinal ischemia/reperfusion in rats].

OBJECTIVE: To observe the change in hepatic and renal functions, change in the plasma D-lactate level, and the expression of proliferating cell nuclear antigen (PCNA) after intestinal I/R injury, so as to explore the effects of reconstructive human acid fibroblast growth factor(aFGF) on intestinal I/R injury in rats. METHODS: One hundred and twenty-six Wistar rats were divided into sham-operated, ischemia (45 minutes) plus reperfusion, reconstructive human aFGF treatment (2, 4, 8 microg aFGF) and wild type aFGF(2, 6, 12, and 24 hours, respectively) groups. Hepatic and renal functions and the levels of plasma D-lactate were determined and the expression of PCNA was assessed. RESULTS: Compared with all other groups, bowel barrier function and hepatic and renal functions showed most marked deterioration in sham-operated group. The damages were less marked in reconstructive human aFGF group compared with other groups 24 hours after ischemia/reperfusion of the intestine, and the protective effect was best shown when 4 microg of aFGF was given. The trend of expression of PCNA was similar to that of changes in D-lactate level. CONCLUSION: Wild type reconstructive human aFGF treatment significantly improves the outcome of ischemia/reperfusion injury to the intestine, and the effect is dose-dependent.

[Protective effects of modified recombinant human acidic fibroblast growth factor on small intestine after ischemia/reperfusion injury in rats].

OBJECTIVE: To explore the protective effect of modified recombinant human acidic fibroblast growth factor (rhaFGF) on small intestinal after ischemia/reperfusion (I/R) injury in rats. METHODS: The clamp on the superior mesenteric artery (SMA) was removed after clamping it for 45 minutes to replicate I/R injury of the intestine in the rat. Rats were then divided randomly into sham operation group, normal saline treatment group and rhaFGF treatment group, in which the rats of the normal saline treatment group were injected 0.1 ml of normal saline and that of the rhaFGF group were given 4 microg of rhaFGF immediately after reperfusion. The content of D-lactate in the plasma was determined and the changes in intestinal pathology were observed. At the same time, the rates of apoptosis of intestinal epithelial cells were assessed 2, 6, 12 and 24 hours after I/R, and compared to the sham operation group. RESULTS: The plasma content of D-lactate in the saline treatment group at 6 hours after I/R reached (0.34+/-0.09) mg/L and was significantly higher than that in the rhaFGF treatment group((0.23+/-0.07)mg/L, P<0.05). It was shown histologically that the intestinal structures were damaged more seriously in saline treatment group than in rhaFGF group. The apoptosis rates in the saline treatment group and rhaFGF group were elevated significantly, peaking at 12 hours after I/R injury((62.8+/-1.7)% in saline group and (42.5+/-2.6)% in rhaFGF treatment group), then the rate began to fall. There was statistically significant difference between the two groups at 12 hours after I/R injury. CONCLUSION: rhaFGF can reduce content of D-lactate in the plasma and rate of apoptosis of epithelial cells in the intestine after I/R injury, thus it seems to afford a protective effect on the small intestine after I/R injury in rats.

[Effects of reconstructive human acidic fibroblast growth factor and wild type acidic fibroblast growth factor on skin cell proliferation].

OBJECTIVE: To investigate the effects of reconstructive human acidic fibroblast growth factor (aFGF) and wild type aFGF on skin cell proliferation in rat. METHODS: Neonatal rat skin (area of 2 mmx2 mm) was cultured in Dulbecco's modification of Eagle's medium containing reconstructive human aFGF and wild type aFGF, respectively. The concentrations of aFGF were 1 microg/L, 10 microg/L, and 100 microg/L. After being cultured for 4 days, the area of skin was measured. RESULTS: After treatment with two different growth factors in three different concentrations (1 microg/L, 10 microg/L and 100 microg/L) for 4 days, the areas of skin in three reconstructive human aFGF groups were 1.4, 1.5 and 1.3 fold of that of control, respectively and the areas of three wild type aFGF groups were 1.5, 3.2 and 1.6 fold of that of control, respectively, while the area of skin in the control group was (2.96+/-1.12) mm(2). In comparison with those of other groups, the skin area of 10 microg/L wild type aFGF group was significantly increased (P<0.05). CONCLUSION: Reconstructive human aFGF confers less impact on cutaneous cell growth. The capability of wild type aFGF to induce cutaneous cell proliferation is much greater than that of reconstructive human aFGF.

[Effects of acidi fibroblast growth factor on hepatic and renal functions after intestinal ischemia/reperfusion injury].

OBJECTIVE: To investigate the change in hepatic and renal functions parameters after intestinal ischemia-reperfusion (I/R) injury, and to explore the effects of acidic fibroblast growth factor (aFGF) on hepatic and renal functions after intestinal I/R injury in rats. METHODS: Seventy-eight Wistar rats were divided into four groups, which are sham-operated (C) group, ischemia (45 minutes) plus reperfusion (R), reconstructive human aFGF treatment (rhF), and wild type aFGF treatment (wtF) groups. The animals were sacrificed at 2, 6, 12 and 24 hours, respectively. Hepatic and renal functions were analyzed. RESULTS: In comparison with those in group C, the hepatic and renal functions were damaged in group R, rhF and wtF decreased. Treatment with rhF and wtF markedly abated the hepatic and renal dysfunction. The desquamation of intestine villi and infiltration of inflammation cells in the submucosa were observed in all groups. CONCLUSION: Hepatic and renal functions are damaged after intestinal I/R injury. Treatment with rhF and wtF could protect against multiple organ dysfunction associated with intestinal ischemia-reperfusiun injury.