Comparative efficacy of six programmed cell death Protein-1 inhibitors as first-line treatment for advanced non-small cell lung cancer: a multicenter retrospective cohort study.

The purpose of this study was to assess the comparative efficacy of six programmed cell death-1 inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) that have been used as first-line therapy for Chinese patients with advanced non-small cell lung cancer (NSCLC), which remains unclear. We determined the differences in efficacy by observing patient survival data, with the goal of informing future treatment options. Retrospective data analysis from June 2015 to April 2023 included 913 patients across six groups: nivolumab (123%, 13.5%), pembrolizumab (421%, 46.1%), sintilimab (239%, 26.1%), tislelizumab (64%, 7.0%), toripalimab (39%, 4.3%), and camrelizumab (27%, 3.0%). The median progression-free survival (PFS) for each group was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and the median overall survival (OS) was 33.7, 36.1, 32.5, not reached, 30.9 and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. While differences existed in the objective response rates among groups (p < 0.05), there were no significant differences (all p > 0.05) in PFS or OS. The findings suggest comparable efficacy among these PD-1 inhibitors for NSCLC treatment, underscoring their collective suitability and aiding treatment decisions.

Prognosis of immune checkpoint inhibitor-induced myasthenia gravis: a single center experience and systematic review.

Background: Immune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves with the clinical characteristics of ICI-induced MG, facilitating early diagnosis and prompt intervention. Methods: We searched the Chinese People's Liberation Army General Hospital medical record system from January 2017 to August 2023 for patients diagnosed with ICI-induced MG. We systematically reviewed the literature until August 2023 to identify all similar patients. We collected clinical information on these patients. Results: 110 patients were identified, 9 from our institution and 101 from case reports. In our institution, Median age was 66 years (range: 49-79 years). 6 were males. The most common was lung cancer (n = 4). All patients had no previous history of MG and received PD-1 or PD-L1 inhibitors. The median time from ICI initiation to first MG symptoms was 4 weeks (range: 2-15 weeks). ICIs were discontinued in all patients. Most patients initially received high-dose corticosteroids, and their symptoms improved. Some patients are discharged with corticosteroids maintenance therapy. In addition, 55 patients (50%) with concomitant myositis and/or myocarditis and MG-induced mortality were more common in the myositis and/or myocarditis group (10.9% vs. 34.5%, p = 0.016). Overlap of myositis with MG (OR = 3.148, p = 0.009) and anti-AChR antibody positivity (OR = 3.364, p = 0.005) were both significantly associated with poor outcomes. Conclusion: Our study reveals the prognosis of ICI-induced MG and suggests that myositis and/or myocarditis are severe comorbidities of ICI-induced MG, emphasizing the importance of early diagnosis and clinical intervention.

Fructus Lycii and Salvia miltiorrhiza Bunge extract attenuate oxidative stress-induced photoreceptor ferroptosis in retinitis pigmentosa.

AIM OF THE STUDY: To assess the impact of Fructus Lycii and Salvia miltiorrhiza Bunge extract (FSE) on retinitis pigmentosa (RP) and to explore the mechanisms by which FSE can prevent oxidative stress-induced photoreceptor ferroptosis in RP. METHODS: Hydrogen peroxide(H2O2) was used to induce oxidative stress in 661 W cells, which were then examined using flow cytometry and enzyme linked immunosorbent assay (ELISA). Changes in mitochondria were observed by using an electron microscope to characterize the ferroptosis of the cells. The protective effect of FSE on the retina function and structure of rd10 mice was evaluated using histopathological examination, fundus photographs, and electroretinography (ERG). Protein expression levels of Tumor Protein p53 (P53), Solute Carrier Family 7 Member 11 (SLC7A11), Glutathione peroxidase 4 (GPX4), Arachidonate-12-Lipoxygenase (ALOX12), and Dipeptidyl peptidase 4 (DPP4) were evaluated by Western blot assays in Vivo and in Vitro. RESULTS: H2O2-induced 661 W cells increased oxidative stress products and P53 and ALOX12, decreasing the expression of SLC7A11, GPX4, and DPP4. GPX4 activator does not reduce reactive oxygen species (ROS) generation and has little effect on ferroptosis. Fer-1 and FSE attenuate ROS generation and inhibit ferroptosis of photoreceptors in RP via inhibited P53 expression and increased SLC7A11 and GPX4 expression. CONCLUSION: FSE may be available in clinical therapeutics to alleviating RP and the mechanism by which inhibits ferroptosis of photoreceptors following oxidative stress via the P53/ SLC7A11 pathway.

Apigenin inhibits angiogenesis in retinal microvascular endothelial cells through regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway.

BACKGROUND: Diabetic retinopathy (DR) is a common cause of visual impairment. Apigenin has been shown to have antiangiogenic effects in various diseases. Our study aimed to investigate the role of apigenin in DR and elucidate the underlying mechanism. METHODS: Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to establish a DR model. HRMECs were treated with apigenin. Then we knocked down or overexpressed miR-140-5p and HDAC3, and added PI3K/AKT inhibitor LY294002. The expression levels of miR-140-5p, HDAC3, and PTEN were measured using qRT-PCR. Western blot analysis was performed to assess the expression of HDAC3, PTEN, and PI3K/AKT pathway-related proteins. Finally, cell proliferation and migration were evaluated using MTT, wound-healing assay, and transwell assay, while angiogenesis was examined using the tube formation assay. RESULTS: HG treatment resulted in reduced miR-140-5p expression and overexpression of miR-140-5p suppressed proliferation, migration, and angiogenesis of the HG-induced HRMECs. Apigenin treatment significantly restored the decreased level of miR-140-5p caused by HG treatment and inhibited proliferation, migration, and angiogenesis of the HG-induced HRMECs by upregulating miR-140-5p. Moreover, miR-140-5p targeted HDAC3, and overexpression of miR-140-5p reversed the HG-inducted upregulation of HDAC3 expression. HDAC3 was found to bind to the promoter region of PTEN, inhibiting its expression. Knockdown of HDAC3 suppressed the PI3K/AKT pathway by elevating PTEN expression. Furthermore, apigenin inhibited angiogenesis in DR cell models through the regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. CONCLUSIONS: Apigenin effectively suppressed angiogenesis in HG-induced HRMECs by modulating the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway. Our study may contribute to the development of novel therapeutic approaches and identification of potential targets for the treatment of DR.

The value of intravoxel incoherent motion model-based diffusion-weighted imaging for predicting long-term outcomes in nasopharyngeal carcinoma.

Objective: The aim of this study was to evaluate the prognostic value for survival of parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in patients with nasopharyngeal carcinoma (NPC). Materials: Baseline IVIM-DWI was performed on 97 newly diagnosed NPC patients in this prospective study. The relationships between the pretreatment IVIM-DWI parametric values (apparent diffusion coefficient (ADC), D, D*, and f) of the primary tumors and the patients' 3-year survival were analyzed in 97 NPC patients who received chemoradiotherapy. The cutoff values of IVIM parameters for local relapse-free survival (LRFS) were identified by a non-parametric log-rank test. The local-regional relapse-free survival (LRRFS), LRFS, regional relapse-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were calculated by using the Kaplan-Meier method. A Cox proportional hazards model was used to explore the independent predictors for prognosis. Results: There were 97 participants (mean age, 48.4 ± 10.5 years; 65 men) analyzed. Non-parametric log-rank test results showed that the optimal cutoff values of ADC, D, D*, and f were 0.897 × 10-3 mm2/s, 0.699 × 10-3 mm2/s, 8.71 × 10-3 mm2/s, and 0.198%, respectively. According to the univariable analysis, the higher ADC group demonstrated significantly higher OS rates than the low ADC group (p = 0.036), the higher D group showed significantly higher LRFS and OS rates than the low D group (p = 0.028 and p = 0.017, respectively), and the higher D* group exhibited significantly higher LRFS and OS rates than the lower D* group (p = 0.001 and p = 0.002, respectively). Multivariable analyses indicated that ADC and D were the independent prognostic factors for LRFS (p = 0.041 and p = 0.037, respectively), D was an independent prognostic factor for LRRFS (p = 0.045), D* and f were the independent prognostic factors for OS (p = 0.019 and 0.029, respectively), and f acted was an independent prognostic factor for DMFS (p = 0.020). Conclusions: Baseline IVIM-DWI perfusion parameters ADC and D, together with diffusion parameter D*, could act as useful factors for predicting long-term outcomes and selecting high-risk patients with NPC.

Epigallocatechin-3-Gallate Ameliorated Iron Accumulation and Apoptosis and Promoted Neuronal Regeneration and Memory/Cognitive Functions in the Hippocampus Induced by Exposure to a Chronic High-Altitude Hypoxia Environment.

We aimed to explore the protective effects and potential treatment mechanism of Epigallocatechin-3-gallate (EGCG) in an animal model of chronic exposure in a natural high-altitude hypoxia (HAH) environment. Behavioral alterations were assessed with the Morris water maze test. Iron accumulation in the hippocampus was detected by using DAB enhanced Perls' staining, MRI, qPCR and colorimetry, respectively. Oxidative stress (malondialdehyde, MDA), apoptosis (Caspase-3), and neural regeneration (brain-derived neurotrophic factor, BDNF) were detected by using ELISA and western blotting. Neural ultrastructural changes were evaluated by transmission electron microscopy (TEM). The results showed that learning and memory performance of rats decreased when exposure to HAH environment. It was followed by iron accumulation, dysfunctional iron metabolism, reduced BDNF and the upregulation of MDA and Caspase-3. TEM confirmed the ultrastructural changes in neurons and mitochondria. EGCG reduced HAH-induced cognitive impairment, iron deposition, oxidative stress, and apoptosis and promoted neuronal regeneration against chronic HAH-mediated neural injury.

Machine learning to differentiate small round cell malignant tumors and non-small round cell malignant tumors of the nasal and paranasal sinuses using apparent diffusion coefficient values.

OBJECTIVE: We used radiomics feature-based machine learning classifiers of apparent diffusion coefficient (ADC) maps to differentiate small round cell malignant tumors (SRCMTs) and non-SRCMTs of the nasal and paranasal sinuses. MATERIALS: A total of 267 features were extracted from each region of interest (ROI). Datasets were randomized into two sets, a training set (∼70%) and a test set (∼30%). We performed dimensional reductions using the Pearson correlation coefficient and feature selection analyses (analysis of variance [ANOVA], relief, recursive feature elimination [RFE]) and classifications using 10 machine learning classifiers. Results were evaluated with a leave-one-out cross-validation analysis. RESULTS: We compared the AUC for all the pipelines in the validation dataset using FeAture Explorer (FAE) software. The pipeline using RFE feature selection and Gaussian process classifier yielded the highest AUCs with ten features. When the "one-standard error" rule was used, FAE produced a simpler model with eight features, including Perc.01%, Perc.10%, Perc.90%, Perc.99%, S(1,0) SumAverg, S(5,5) AngScMom, S(5,5) Correlat, and WavEnLH_s-2. The AUCs of the training, validation, and test datasets achieved 0.995, 0.902, and 0.710, respectively. For ANOVA, the pipeline with the auto-encoder classifier yielded the highest AUC using only one feature, Perc.10% (training/validation/test datasets: 0.886/0.895/0.809, respectively). For the relief, the AUCs of the training, validation, and test datasets that used the LRLasso classifier using five features (Perc.01%, Perc.10%, S(4,4) Correlat, S(5,0) SumAverg, S(5,0) Contrast) were 0.892, 0.886, and 0.787, respectively. Compared with the RFE and relief, the results of all algorithms of ANOVA feature selection were more stable with the AUC values higher than 0.800. CONCLUSIONS: We demonstrated the feasibility of combining artificial intelligence with the radiomics from ADC values in the differential diagnosis of SRCMTs and non-SRCMTs and the potential of this non-invasive approach for clinical applications. KEY POINTS: • The parameter with the best diagnostic performance in differentiating SRCMTs from non-SRCMTs was the Perc.10% ADC value. • Results of all the algorithms of ANOVA feature selection were more stable and the AUCs were higher than 0.800, as compared with RFE and relief. • The pipeline using RFE feature selection and Gaussian process classifier yielded the highest AUC.

Texture Analysis of Fat-Suppressed T2-Weighted Magnetic Resonance Imaging and Use of Machine Learning to Discriminate Nasal and Paranasal Sinus Small Round Malignant Cell Tumors.

OBJECTIVE: We used texture analysis and machine learning (ML) to classify small round cell malignant tumors (SRCMTs) and Non-SRCMTs of nasal and paranasal sinus on fat-suppressed T2 weighted imaging (Fs-T2WI). MATERIALS: Preoperative MRI scans of 164 patients from 1 January 2018 to 1 January 2021 diagnosed with SRCMTs and Non-SRCMTs were included in this study. A total of 271 features were extracted from each regions of interest. Datasets were randomly divided into two sets, including a training set (∼70%) and a test set (∼30%). The Pearson correlation coefficient (PCC) and principal component analysis (PCA) methods were performed to reduce dimensions, and the Analysis of Variance (ANOVA), Kruskal-Wallis (KW), and Recursive Feature Elimination (RFE) and Relief were performed for feature selections. Classifications were performed using 10 ML classifiers. Results were evaluated using a leave one out cross-validation analysis. RESULTS: We compared the AUC of all pipelines on the validation dataset with FeAture Explorer (FAE) software. The pipeline using a PCC dimension reduction, relief feature selection, and gaussian process (GP) classifier yielded the highest area under the curve (AUC) using 15 features. When the "one-standard error" rule was used, FAE also produced a simpler model with 13 features, including S(5,-5)SumAverg, S(3,0)InvDfMom, Skewness, WavEnHL_s-3, Horzl_GlevNonU, Horzl_RLNonUni, 135dr_GlevNonU, WavEnLL_s-3, Teta4, Teta2, S(5,5)DifVarnc, Perc.01%, and WavEnLH_s-2. The AUCs of the training/validation/test datasets were 1.000/0.965/0.979, and the accuracies, sensitivities, and specificities were 0.890, 0.880, and 0.920, respectively. The best algorithm was GP whose AUCs of the training/validation/test datasets by the two-dimensional reduction methods and four feature selection methods were greater than approximately 0.800. Especially, the AUCs of different datasets were greater than approximately 0.900 using the PCC, RFE/Relief, and GP algorithms. CONCLUSIONS: We demonstrated the feasibility of combining artificial intelligence and the radiomics from Fs-T2WI to differentially diagnose SRCMTs and Non-SRCMTs. This non-invasive approach could be very promising in clinical oncology.

A meta-analysis of the diagnostic performance of machine learning-based MRI in the prediction of axillary lymph node metastasis in breast cancer patients.

BACKGROUND: Despite that machine learning (ML)-based MRI has been evaluated for diagnosis of axillary lymph node metastasis (ALNM) in breast cancer patients, diagnostic values they showed have been variable. In this study, we aimed to assess the use of ML to classify ALNM on MRI and to identify potential covariates that might influence the diagnostic performance of ML. METHODS: A systematic research of PubMed, Embase, Web of Science, and the Cochrane Library was conducted until 27 December 2020 to collect the included articles. Subgroup analysis was also performed. FINDINGS: Fourteen studies assessing a total of 2247 breast cancer patients were included in the analysis. The overall AUC for ML in the validation set was 0.80 (95% confidence interval [CI] 0.76-0.83) with a negative predictive value of 0.83. The pooled sensitivity and specificity were 0.79 (95% CI 0.74-0.84) and 0.77 (95% CI 0.73-0.81), respectively. In the subgroup analysis of the validation set, T1-weighted contrast-enhanced (T1CE) imaging with ML yielded a higher sensitivity (0.80 vs. 0.67 vs. 0.76) than the T2-weighted fat-suppressed (T2-FS) imaging and diffusion-weighted imaging (DWI). Support vector machines (SVMs) had a higher specificity than linear regression (LR) and linear discriminant analysis (LDA) (0.79 vs. 0.78 vs. 0.75), whereas LDA showed a higher sensitivity than LR and SVM (0.83 vs. 0.70 vs. 0.77). INTERPRETATION: MRI sequences and algorithms were the main factors that affect the diagnostic performance of ML. Although its results were encouraging with the pooled sensitivity of around 0.80, it meant that 1 in 5 women that would go with undetected metastases, which may have a detrimental effect on the overall survival for 20% of patients with positive SLN status. Despite that a high NPV of 0.83 meant that ML could potentially benefit those with negative SLN, it might also translate to 1 in 5 tests being false negative. We would like to suggest that ML may not be yet usable in clinical routine especially when patient survival is used as a primary measurement of its outcome.

Effect of Shuangdan Mingmu capsule, a Chinese herbal formula, on oxidative stress-induced apoptosis of pericytes through PARP/GAPDH pathway.

BACKGROUND: Diabetic retinopathy (DR) has become a worldwide concern because of the rising prevalence rate of diabetes mellitus (DM). Despite much energy has been committed to DR research, it remains a difficulty for diabetic patients all over the world. Since apoptosis of retinal microvascular pericytes (RMPs) is the early characteristic of DR, this study aimed to reveal the mechanism of Shuangdan Mingmu (SDMM) capsule, a Chinese patent medicine, on oxidative stress-induced apoptosis of pericytes implicated with poly (ADP-ribose) polymerase (PARP) / glyceraldehyde 3-phosphate dehydrogenase (GAPDH) pathway. METHODS: Network pharmacology approach was performed to predict biofunction of components of SDMM capsule dissolved in plasma on DR. Both PARP1 and GAPDH were found involved in the hub network of protein-protein interaction (PPI) of potential targets and were found to take part in many bioprocesses, including responding to the regulation of reactive oxygen species (ROS) metabolic process, apoptotic signaling pathway, and response to oxygen levels through enrichment analysis. Therefore, in vitro research was carried out to validate the prediction. Human RMPs cultured with media containing 0.5 mM hydrogen oxide (H2O2) for 4 h was performed as an oxidative-damage model. Different concentrations of SDMM capsule, PARP1 inhibitor, PARP1 activation, and GAPDH inhibitor were used to intervene the oxidative-damage model with N-Acetyl-L-cysteine (NAC) as a contrast. Flow cytometry was performed to determine the apoptosis rate of cells and the expression of ROS. Cell counting kit 8 (CCK8) was used to determine the activity of pericytes. Moreover, nitric oxide (NO) concentration of cells supernatant and expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), B cell lymphoma 2 (BCL2), vascular endothelial growth factor (VEGF), endothelin 1 (ET1), PARP1, and GAPDH were tested through RT-qPCR, western blot (WB), or immunocytochemistry (ICC). RESULTS: Overproduction of ROS, high apoptotic rate, and attenuated activity of pericytes were observed after cells were incubated with media containing 0.5 mM H2O2. Moreover, downregulation of SOD, NO, BCL2, and GAPDH, and upregulation of VEGFA, ET1, and PARP1 were discovered after cells were exposed to 0.5 mM H2O2 in this study, which could be improved by PARP1 inhibitor and SDMM capsule in a dose-dependent way, whereas worsened by PARP1 activation and GAPDH inhibitor. CONCLUSIONS: SDMM capsule may attenuate oxidative stress-induced apoptosis of pericytes through downregulating PARP expression and upregulating GAPDH expression.

Predicting the pathological response to chemoradiotherapy of non-mucinous rectal cancer using pretreatment texture features based on intravoxel incoherent motion diffusion-weighted imaging.

OBJECTIVES: To investigate the performance of the mean parametric values and texture features based on intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) on identifying pathological complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). METHODS: Pretreatment IVIM-DWI was performed on 41 LARC patients receiving nCRT in this prospective study. The values of IVIM-DWI parameters (apparent diffusion coefficient, ADC; pure diffusion coefficient, D; pseudo-diffusion coefficient, D* and perfusion fraction, f), the first-order, and gray-level co-occurrence matrix (GLCM) texture features were compared between the pCR (n = 9) and non-pathological responder (non-pCR, n = 32) groups. Receiver operating characteristic (ROC) curves in univariate and multivariate logistic regression analysis were generated to determine the efficiency for identifying pCR. RESULTS: The values of IVIM-DWI parameters and first-order texture features did not show significant differences between the pCR and non-pCR groups. The pCR group had lower Contrast and DifVarnc values extracted from the ADC, D, and D* maps, respectively, as well as lower CorrelatD value. Higher CorrelatD*, Correlatf, SumAvergADC, and SumAvergD values were observed in the pCR group. The area under the ROC curve (AUC) values for the individual predictors in univariate analysis ranged from 0.698 to 0.837, with sensitivities from 43.75% to 87.50% and specificities from 66.67 to 100.00%. In multivariate analysis, CorrelatD* (P < 0.001), DifVarncADC (P = 0.024), and DifVarncD (P < 0.001) were the independent predictors to pCR, with an AUC of 0.986, a sensitivity of 93.75%, and a specificity of 100.00%. CONCLUSION: Pretreatment GLCM analysis based on IVIM-DWI may be a potential approach to identify the pathological response of LARC.

Prognostic Value of the Pretreatment Primary Lesion Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Nasopharyngeal Carcinoma.

RATIONALE AND OBJECTIVES: Early identifying the long-term outcome of chemoradiotherapy is helpful for personalized treatment in nasopharyngeal carcinoma (NPC). This study aimed to investigate the prognostic significance of pretreatment quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for NPC. MATERIALS AND METHODS: The relationships between the prognosis and pretreatment quantitative DCE-MRI (Ktrans, Kep, Ve, and fpv) values of the primary tumors were analyzed in 134 NPC patients who received chemoradiotherapy. Kaplan-Meier analysis was performed to calculate the local-regional relapse-free survival (LRRFS), local relapse-free survival (LRFS), regional relapse-free survival, distant metastasis-free survival (DMFS), progression-free survival, and overall survival rates. Cox proportional hazards model was used to explore the independent predictors for prognosis. RESULTS: The local-failure group had significantly higher Ve (p = 0.033) and fpv values (p = 0.005) than the non-local-failure group. The Ve-high group showed significantly lower LRRFS (p = 0.015) , LRFS (p = 0.013) , DMFS (p = 0.027) and progression-free survival (p = 0.035) rates than the Ve-low group. The fpv-high group exhibited significantly lower LRRFS (p = 0.004) and LRFS (p = 0.005) rates than the fpv-low group. Ve was the independent predictor for LRRFS (p = 0.008), LRFS (p = 0.007), DMFS (p = 0.041), and overall survival (p = 0.022). fpv was the independent indicator for LRRFS (p = 0.003) and LRFS (p = 0.001). CONCLUSION: Baseline quantitative DCE-MRI may be valuable in predicting the prognosis for NPC.

Predicting chemoradiotherapy response of nasopharyngeal carcinoma using texture features based on intravoxel incoherent motion diffusion-weighted imaging.

The aim of the study was to investigative the utility of gray-level co-occurrence matrix (GLCM) texture analysis based on intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for predicting the early response to chemoradiotherapy for nasopharyngeal carcinoma (NPC).Baseline IVIM-DWI was performed on 81 patients with NPC receiving chemoradiotherapy in a prospective nested case-control study. The patients were categorized into the residue (n = 11) and nonresidue (n = 70) groups, according to whether there was local residual lesion or not at the end of chemoradiotherapy. The pretreatment tumor volume and the values of IVIM-DWI parameters (apparent diffusion coefficient [ADC], D, D, and f) and GLCM features based on IVIM-DWI were compared between the 2 groups. Receiver operating characteristic (ROC) curves in univariate and multivariate logistic regression analysis were generated to determine significant indicator of treatment response.The nonresidue group had lower tumor volume, ADC, D, CorrelatADC, CorrelatD, InvDfMomADC, InvDfMomD and InvDfMomD values, together with higher ContrastD, Contrastf, SumAvergADC, SumAvergD, and SumAvergD values, than the residue group (all P < .05). Based on ROC curve in univariate analysis, the area under the curve (AUC) values for individual GLCM features in the prediction of the treatment response ranged from 0.635 to 0.879, with sensitivities from 54.55% to 100.00% and specificities from 52.86% to 85.71%. Multivariate logistic regression analysis demonstrated D (P = .026), InvDfMomADC (P = .033) and SumAvergD (P = .015) as the independent predictors for identifying NPC without residue, with an AUC value of 0.977, a sensitivity of 90.91% and a specificity of 95.71%.Pretreatment GLCM features based on IVIM-DWI, especially on the diffusion-related maps, may have the potential to predict the early response to chemoradiotherapy for NPC.

MiR-340/iASPP axis affects UVB-mediated retinal pigment epithelium (RPE) cell damage.

Long-term exposure to ultraviolet B (UVB) light increases the risk of UVB damage due to increased UVB absorption by the retina and may further lead to age-related eye diseases. The retinal pigment epithelium (RPE) cell is a main target of UVB reaching the retina; its degeneration is an essential event in UVB-mediated age-related macular degeneration (AMD). Herein, we first evaluated the expression and effect of iASPP, an inhibitory regulator of apoptosis, in UVB-induced RPE cell damage. Through the mechanism of RNA interference at the post-transcriptional level, miRNA affects a variety of cellular processes, including UVB-mediated cell damage. We next screened for upstream candidate miRNAs that may regulate iASPP expression. Among 8 candidate miRNAs, UVB significantly increased miR-340 levels. We also confirmed the direct binding of miR-340 to the 3'UTR of iASPP, and assessed the combined effect of miR-340 and iASPP on UVB-induced RPE cell damage. Taken together, we demonstrated the possible mechanisms involved in UVB-induced retinal damage. In RPE cells, UVB irradiation inhibits iASPP expression through inducing miR-340 expression, thereby promoting RPE cell apoptosis and suppressing cell viability via affecting p53, p21 and caspase-3 protein expression. Targeting miR-340 to rescue iASPP expression in RPE cells may help treat UVB-mediated retinal damage.

The pharmacological properties of Ophiocordyceps xuefengensis revealed by transcriptome analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The Yao ethnic group in Xuefeng Mountains area have used Xuefeng cordyceps, the caterpillar-fungus complex of Ophiocordyceps xuefengensis, for treating a variety of diseases for long. Just like some other cordyceps, O. xuefengensis, which is identified as the sister taxon of O. sinensis in 2013, also seems to have broad pharmacological properties, not only enhancing human immunity, anti-bacteria, anti-virus, but also anti-tumor. However, investigation of the medicinal fugal species O. xuefengensis can be found only in few literature records since its pharmacological and therapeutic use is mainly in traditional Yao communities by local healers. AIM OF THE STUDY: The aim of this study is to collect samples of Xuefeng cordyceps and isolate the strain of O. xuefengensis, to determine bioactive components and evaluate the anti-tumor activity, to obtain the gene expression profile of O. xuefengensis and reveal its pharmacological properties by de novo transcriptome analysis. Accordingly, we attempt to provide information and give a comprehensive understanding of this mysterious medicinal fugal species from traditional Yao communities of China. MATERIAL AND METHODS: Bioactive components were determined with HPLC-DAD-Q-TOF-MS technology; in vitro anti-tumor activity against 6 cell lines was evaluated using standard MTT assay; transcriptome analysis was done by de novo sequencing; unique genes were functionally profiled basing on Gene Ontology Database and the targeted genes were examined by blast. RESULTS: Trace cordycepin, an anti-tumor agent, was detected in O. xuefengensis water extract. To some extent, the raw water extract of O. xuefengensis showed in vitro anti-tumor activity, against A549, HepG2, MCF-7, PC-3 and Raji cell lines. A total of 94,858 transcripts and 49,001 unique genes were obtained, amongst, 43.4% unique genes were matched with those of O. sinensis. Not all supposed genes related to cordycepin biosynthetic pathways were found by transcriptome analysis. CONCLUSION: According to the gene expression profile, O. xuefengensis is very close to medicinal fungus O. sinensis. Raw water extract of O. xuefengensis, to a certain degree, could inhibit the growth of tumor cells, indicating that this fungus could be a new resource for the exploration of anti-tumor drug.

A new cordycepin-producing caterpillar fungus Ophiocordyceps xuefengensis with artificial infection to the host, cultivation of mycelia and stromata.

Caterpillar fungi have numerous pharmacological and therapeutic applications in traditional medicine, due to a variety of active chemical constituents, such as cordycepin and adenosine. It is imperative to discover new resource for artificial cultivation and biometabolite production since the traditional natural species are endangered. In this study, a new strain HACM 001 was isolated and identified as Ophiocordyceps xuefengensis by rDNA-ITS sequencing. This strain showed the potential of artificial infection to caterpillar larvae leading to mummification, as well as fermentation mycelia in liquid culture and cultivation stromata in solid medium. Eight nucleosides and nucleobases, especially cordycepin and adenosine, were determined and analyzed with HPLC-DAD-Q-TOF-MS/MS technology. Cordycepin was detected in all forms of present O. xuefengensis strain at different contents, among which the highest content (37.1 µg/g) appeared in the stromata cultivated on solid medium. The content of adenosine in mycelia and stromata, respectively, reached 1155 µg/g and 1470 µg/g. Therefore, O. xuefengensis might be an alternative source for obtaining artificial fungus-caterpillar-larvae complex and producing cordycepin and adenosine.