The Application of CT Radiomics in the Diagnosis of Vein Wall Invasion in Patients With Renal Cell Carcinoma Combined With Tumor Thrombus.

OBJECTIVE: The objective of this study was to explore the application of radiomics combined with machine learning to establish different models to assist in the diagnosis of venous wall invasion in patients with renal cell carcinoma and venous tumor thrombus and to evaluate the diagnostic efficacy. MATERIALS AND METHODS: We retrospectively reviewed the data of 169 patients in Peking University Third Hospital from March 2015 to January 21, who was diagnosed as renal mass with venous invasion. According to the intraoperative findings, 111 patients were classified to the venous wall invasion group and 58 cases in the non-invasion group. ITK-snap was used for tumor segmentation and PyRadiomics 3.0.1 package was used for feature extraction. A total of 1598 features could be extracted from each CT image. The patients were divided into training set and testing set by time. The elastic-net regression with 4-fold cross-validation was used as a dimension-reduction method. After feature selection, a support vector machines (SVM) model, a logistic regression (LR) model, and an extra trees (ET) model were established. Then the sensitivity, specificity, accuracy, and the area under the curve (AUC) were calculated to evaluate the diagnostic performance of each model on the testing set. RESULTS: Patients before September 2019 were divided into the training set, of which 88 patients were in the invasion group and 42 patients were in the non-invasion group. The others were in the testing set, of which 32 patients were in the invasion group and 16 patients were in the non-invasion group. A total of 34 radiomics features were obtained by the elastic-net regression. The SVM model had an AUC value of 0.641 (95% CI, 0.463-0.769), a sensitivity of 1.000, and a specificity of 0.062. The LR model had an AUC value of 0.769 (95% CI, 0.620-0.877), a sensitivity of 0.913, and a specificity of 0.312. The ET model had an AUC value of 0.853 (95% CI, 0.734-0.948), a sensitivity of 0.783, and a specificity of 0.812. Among the 3 models, the ET model had the best diagnostic effect, with a good balance of sensitivity and specificity. And the higher the tumor thrombus grade, the better the diagnostic efficacy of the ET model. In inferior vena cava tumor thrombus, the sensitivity, specificity, accuracy, and AUC of ET model can be improved to 0.889, 0.800, 0.857, 0.878 (95% CI, 0.745-1.000). CONCLUSION: Machine learning combined with radiomics method can effectively identify whether venous wall was invaded by tumor thrombus and has high diagnostic efficacy with an AUC of 0.853 (95% CI, 0.734-0.948).

Dual Function of the Third Component in Ternary Organic Solar Cells: Broaden the Spectrum and Optimize the Morphology.

Ternary organic solar cells (T-OSCs) have attracted significant attention as high-performance devices. In recent years, T-OSCs have achieved remarkable progress with power conversion efficiency (PCE) exceeding 19%. However, the introduction of the third component complicates the intermolecular interaction compared to the binary blend, resulting in poor controllability of active layer and limiting performance improvement. To address these issues, dual-functional third components have been developed that not only broaden the spectral range but also optimize morphology. In this review, the effect of the third component on expanding the absorption range of T-OSCs is first discussed. Second, the extra functions of the third component are introduced, including adjusting the crystallinity and molecular stack in active layer, regulating phase separation and purity, altering molecular orientation of the donor or acceptor. Finally, a summary of the current research progress is provided, followed by a discussion of future research directions.

Utility of contrast-enhanced MRI radiomics features combined with clinical indicators for predicting induction chemotherapy response in primary central nervous system lymphoma.

PURPOSE: To assess the utility of combining contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics features with clinical variables in predicting the response to induction chemotherapy (IC) for primary central nervous system lymphoma (PCNSL). METHODS: A total of 131 patients with PCNSL (101 in the training set and 30 in the testing set) who had undergone contrast-enhanced MRI scans were retrospectively analyzed. Pyradiomics was utilized to extract radiomics features, and the clinical variables of the patients were gathered. Radiomics prediction models were developed using different combinations of feature selection methods and machine learning models, and the best combination was ultimately chosen. We screened clinical variables associated with treatment outcomes and developed clinical prediction models. The predictive performance of radiomics model, clinical model, and combined model, which integrates the best radiomics model and clinical characteristics, was independently assessed and compared using Receiver Operating Characteristic (ROC) curves. RESULTS: In total, we extracted 1598 features. The best radiomics model we selected as the best utilized T-test and Recursive Feature Elimination (RFE) for feature selection and logistic regression for model building. Serum Interleukin 2 Receptor (IL-2R) and Eastern Cooperative Oncology Group (ECOG) Score were utilized to develop a clinical predictive model for assessing the response to induction chemotherapy. The results of the testing set revealed that the combined prediction model (radiomics and IL-2R) achieved the highest area under the ROC curve at 0.868 (0.683, 0.967), followed by the radiomics model at 0.857 (0.681, 0.957), and the clinical prediction model (IL-2R and ECOG) at 0.618 (0.413, 0.797). The combined model was significantly more accurate than the clinical model, with an AUC of 0.868 compared to 0.618 (P < 0.05). While the radiomics model had slightly better predictive power than the clinical model, this difference was not statistically significant (AUC, 0.857 vs. 0.618, P > 0.05). CONCLUSIONS: Our prediction model, which combines radiomics signatures from CE-MRI with serum IL-2R, can effectively stratify patients with PCNSL before high-dose methotrexate (HD-MTX) -based chemotherapy.

Face recognition ability can be predicted by microstructural properties of white matter: a study of diffusion tensor imaging (DTI).

There is a great individual difference in people's face recognition ability (FRA). This study aimed to reveal the neural mechanism underlying such individual differences. Elastic-net regression models were constructed to predict FRA based on the white matter (WM) microstructural properties. We found that FRA can be accurately predicted by the WM microstructural properties. For the right inferior longitudinal fasciculus (ILF) and bilateral arcuate fasciculus (AF), FRA was correlated negatively to fractional anisotropy (FA), but positively to radial diffusivity (RD). In contrast, for the corpus callosum forceps minor (CFM), FRA was correlated positively to FA, but negatively to RD. Such various patterns of the WM microstructural properties suggested a positive correlation between FRA and fiber diameter for the right ILF and bilateral AF, but a negative correlation between FRA and diameter of the CFM. These findings reflected that FRA was correlated positively to connectivities of the right ILF and bilateral AF, but negatively to those of the CFM. These findings not only confirmed the significant role of the right ILF in face recognition, but also revealed the involvement of the bilateral AF and CFM in face recognition, particularly implying the important role of hemisphere lateralization modulated by transcallosal connectivity in face recognition.

Predicting clinically significant prostate cancer with a deep learning approach: a multicentre retrospective study.

PURPOSE: This study aimed to develop deep learning (DL) models based on multicentre biparametric magnetic resonance imaging (bpMRI) for the diagnosis of clinically significant prostate cancer (csPCa) and compare the performance of these models with that of the Prostate Imaging and Reporting and Data System (PI-RADS) assessment by expert radiologists based on multiparametric MRI (mpMRI). METHODS: We included 1861 consecutive male patients who underwent radical prostatectomy or biopsy at seven hospitals with mpMRI. These patients were divided into the training (1216 patients in three hospitals) and external validation cohorts (645 patients in four hospitals). PI-RADS assessment was performed by expert radiologists. We developed DL models for the classification between benign and malignant lesions (DL-BM) and that between csPCa and non-csPCa (DL-CS). An integrated model combining PI-RADS and the DL-CS model, abbreviated as PIDL-CS, was developed. The performances of the DL models and PIDL-CS were compared with that of PI-RADS. RESULTS: In each external validation cohort, the area under the receiver operating characteristic curve (AUC) values of the DL-BM and DL-CS models were not significantly different from that of PI-RADS (P > 0.05), whereas the AUC of PIDL-CS was superior to that of PI-RADS (P < 0.05), except for one external validation cohort (P > 0.05). The specificity of PIDL-CS for the detection of csPCa was much higher than that of PI-RADS (P < 0.05). CONCLUSION: Our proposed DL models can be a potential non-invasive auxiliary tool for predicting csPCa. Furthermore, PIDL-CS greatly increased the specificity of csPCa detection compared with PI-RADS assessment by expert radiologists, greatly reducing unnecessary biopsies and helping radiologists achieve a precise diagnosis of csPCa.

A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer.

BACKGROUND: In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab. METHODS: Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor ß receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive. RESULTS: This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available. CONCLUSIONS: The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort. TRIAL REGISTRATION: Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).

Detecting Adverse Pathology of Prostate Cancer With a Deep Learning Approach Based on a 3D Swin-Transformer Model and Biparametric MRI: A Multicenter Retrospective Study.

BACKGROUND: Accurately detecting adverse pathology (AP) presence in prostate cancer patients is important for personalized clinical decision-making. Radiologists' assessment based on clinical characteristics showed poor performance for detecting AP presence. PURPOSE: To develop deep learning models for detecting AP presence, and to compare the performance of these models with those of a clinical model (CM) and radiologists' interpretation (RI). STUDY TYPE: Retrospective. POPULATION: Totally, 616 men from six institutions who underwent radical prostatectomy, were divided into a training cohort (508 patients from five institutions) and an external validation cohort (108 patients from one institution). FIELD STRENGTH/SEQUENCES: T2-weighted imaging with a turbo spin echo sequence and diffusion-weighted imaging with a single-shot echo plane-imaging sequence at 3.0 T. ASSESSMENT: The reference standard for AP was histopathological extracapsular extension, seminal vesicle invasion, or positive surgical margins. A deep learning model based on the Swin-Transformer network (TransNet) was developed for detecting AP. An integrated model was also developed, which combined TransNet signature with clinical characteristics (TransCL). The clinical characteristics included biopsy Gleason grade group, Prostate Imaging Reporting and Data System scores, prostate-specific antigen, ADC value, and the lesion maximum cross-sectional diameter. STATISTICAL TESTS: Model and radiologists' performance were assessed using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The Delong test was used to evaluate difference in AUC. P < 0.05 was considered significant. RESULTS: The AUC of TransCL for detecting AP presence was 0.813 (95% CI, 0.726-0.882), which was higher than that of TransNet (0.791 [95% CI, 0.702-0.863], P = 0.429), and significantly higher than those of CM (0.749 [95% CI, 0.656-0.827]) and RI (0.664 [95% CI, 0.566-0.752]). DATA CONCLUSION: TransNet and TransCL have potential to aid in detecting the presence of AP and some single adverse pathologic features. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 4.

Aberrant Topological Properties of Brain Functional Network in Children with Obstructive Sleep Apnea Derived from Resting-State fMRI.

To examine the difference in the topological properties of brain functional network between the children with obstructive sleep apnea (OSA) and healthy controls, and to explore the relationships between these properties and cognitive scores of OSA children. Twenty-four OSA children (6.5 ± 2.8 years, 15 males) and 26 healthy controls (8.0 ± 2.9 years, 11 males) underwent resting-state fMRI (rs-fMRI), based on which brain functional networks were constructed. We compared the global and regional topological properties of the network between OSA children and healthy controls. Partial correlation analysis was performed between topological properties and cognitive scores across OSA children. When comparing the OSA children with the healthy controls, lower full-scale intelligent quotient (FIQ) and verbal intelligent quotient (VIQ) were observed. Additionally, nodal degree centrality decreased in the bilateral anterior cingulate and paracingulate gyrus, but increased in the right middle frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Nodal efficiency decreased in the right precentral gyrus, and the bilateral anterior cingulate and paracingulate gyrus, but increased in the left fusiform gyrus. Nodal betweenness centrality increased in the dorsolateral part of the right superior frontal gyrus, the left fusiform gyrus, and the left supramarginal gyrus. Further, the nodal degree centrality in the left supramarginal gyrus was positively correlated with FIQ. In contrast, none of global topological properties showed difference between those two groups. The outcomes of OSA may impaired the regional topological properties of the brain functional network of OSA children, which may be potential neural mechanism underlying the cognitive declines of these patients.

Analysis of the efficacy of microdissection of paravebous sinus meningiomas invading large venous sinuses.

OBJECTIVE: The management of paravebous sinus meningiomas that invade major venous sinuses is a subject of debate, particularly concerning the necessity of complete resection of the tumor and reconstruction of the venous sinus. This article aims to demonstrate the outcomes of total removal of the lesion (including the invading venous sinus portion) and the effects of restoring or not restoring venous circulation in terms of recurrence of the tumor, mortality, and post-operative complications. METHODS: The authors conducted a study involving 68 patients with paravebous sinus meningiomas. Of the 60 parasagittal meningiomas, 23 were located in the anterior third, 30 in the middle third, and 7 in the posterior third. Additionally, 3 lesions were located in the sinus confluence area, and 5 in the transverse sinus. All patients underwent surgery, and the degree of venous sinus involvement was classified into six types. For type I meningiomas, the outer layer of the sinus wall was stripped off. For types II to VI, two strategies were employed: non-constitutional, wherein the tumor and affected venous sinuses were removed without repair, and reconstructive, wherein the tumor was completely removed and the venous sinuses were sutured or repaired. Karnofsky Performance Status (KPS) scale and Magnetic Resonance Venography (MRV) were utilized to assess the outcomes of the surgical procedures. RESULTS: The study group of 68 patients underwent complete tumor resection in 97.1%, with sinus reconstruction attempted in 84.4% of cases with sinus wall and sinus cavity invasion. The recurrence rate of this group was 5.9%, with follow-up ranging from 33 to 57 months. It was found that the recurrence rate was significantly higher in cases with incomplete resection than in those with complete resection. The overall mortality rate was 4.4%, with all cases resulting from malignant brain swelling due to the failure to perform venous reconstruction after resectioning of the meningioma type VI. Furthermore, 10.3% of patients experienced worsening symptoms of neurological deficits or complete loss of neurological function, with a significantly higher incidence in those without venous reconstruction than in the venous reconstruction group (P < 0.0001, Fisher test). No statistically significant pre-operative and post-operative KPS differences were observed in patients with type I to V. However, in patients with type VI (who did not receive venous reconstruction), the post-operative KPS score was significantly worse. CONCLUSION: The results of this study suggest the necessity of a complete resection of the tumor, including the invasive venous sinus component, as the recurrence rate was found to be relatively low at 5.9%. Moreover, patients who did not undergo venous reconstruction showed significant deterioration in their clinical condition compared to other subgroups, thus highlighting the importance of venous sinus reconstruction.

Blending Donors with Different Molecular Weights: An Efficient Strategy to Resolve the Conflict between Coherence Length and Intermixed Phase in Polymer/Nonfullerene Solar Cells.

Long coherence lengths (CLs) of crystals and proper intermixed phase amount guarantee charge transport and exciton dissociate efficiently, which is crucial for organic solar cells (OSCs) to achieve high device performance. However, extending CLs usually reduces the intermixed phase, leading to an insufficient interface for exciton dissociation. Herein, a strategy using a binary polymer with different molecular weights as donor is employed, that is, poly(3-hexylthiophene-2,5-diyl) (P3HT) with high (P3HT-H) and low (P3HT-L) molecular weight are blended as donor, and (5Z,5'Z)-5,5'-(((4,4,9,9-tetraoctyl-4,9-dihydro-s-indaceno[1,2-b:5,6-b']dithiophene-2,7-diyl)bis(benzo[c][1,2,5]thiadiazole-7,4-diyl))bis(methanylylidene))bis(3-ethyl-2-thioxothiazolidin-4-one) (O-IDTBR) is used as acceptor. In kinetics, the entanglements of P3HT-H are relieved due to the higher molecular diffusivity of P3HT-L. In thermodynamics, the miscibility of P3HT-L/O-IDTBR, P3HT-H/O-IDTBR, and P3HT-L/P3HT-H blends increases in turn. Hence, P3HT forms a more ordered structure with longer CLs after adding P3HT-L, which also drives O-IDTBR dispersed in P3HT crystalline regions diffuse to the O-IDTBR crystalline regions to further self-organize. Consequently, the CLs of both P3HT and O-IDTBR are extended, while keeping the intermixed phase amount proper. The optimized microstructure boosts device performance from 7.03% to 7.80%, which is one of the highest values reported for P3HT/O-IDTBR blends. This is a novel way to solve the conflict mentioned above, which may provide guidance to finely regulating the morphology of the active layer.

Addition of ramucirumab or merestinib to standard first-line chemotherapy for locally advanced or metastatic biliary tract cancer: a randomised, double-blind, multicentre, phase 2 study.

BACKGROUND: Biliary tract cancers are aggressive, rare, gastrointestinal malignancies with a poor prognosis; approximately half of patients with these cancers survive for less than 1 year after diagnosis with advanced disease. We aimed to evaluate the efficacy and safety of ramucirumab or merestinib in addition to first-line cisplatin-gemcitabine in patients with locally advanced or metastatic biliary tract cancer. METHODS: We did a randomised, double-blind, phase 2 study at 81 hospitals across 18 countries. We enrolled patients with histologically or cytologically confirmed, non-resectable, recurrent, or metastatic biliary tract adenocarcinoma, who were treatment-naive, aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0 or 1, estimated life expectancy of 3 months or more, and measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1. Eligible participants were randomly assigned (2:1:2:1) to receive either intravenous ramucirumab 8 mg/kg or placebo (on days 1 and 8 in 21-day cycles) or oral merestinib 80 mg or placebo (once daily) until disease progression, unacceptable toxicity, death, or patient or investigator request for discontinuation. All participants received intravenous cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 (on days 1 and 8 in 21-day cycles), for a maximum of eight cycles. Randomisation was done by an interactive web response system using a permuted block method (blocks of six) and was stratified by primary tumour site, geographical region, and presence of metastatic disease. Participants, investigators, and the study funder were masked to treatment assignment within the intravenous and oral groups. The primary endpoint was investigator-assessed progression-free survival (in the intention-to-treat population). The safety analysis was done in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT02711553, and long-term follow-up is ongoing. FINDINGS: Between May 25, 2016, and Aug 8, 2017, 450 patients were assessed for eligibility and 309 (69%) were enrolled and randomly assigned to ramucirumab (n=106), merestinib (n=102), or pooled placebo (n=101); 306 received at least one dose of study treatment. The median follow-up time for progression-free survival at data cutoff (Feb 16, 2018) was 10·9 months (IQR 8·1-14·1). Median progression-free survival was 6·5 months (80% CI 5·7-7·1) in the ramucirumab group, 7·0 months (6·2-7·1) in the merestinib group, and 6·6 months (5·6-6·8) in the pooled placebo group (ramucirumab vs placebo hazard ratio 1·12 [80% CI 0·90-1·40], two-sided stratified p=0·48; merestinib vs placebo 0·92 [0·73-1·15], two-sided stratified p=0·64). The most common grade 3 or worse adverse events were neutropenia (51 [49%] of 104 patients in the ramucirumab group; 48 [47%] of 102 in the merestinib group; and 33 [33%] of 100 in the pooled placebo group), thrombocytopenia (36 [35%]; 19 [19%]; and 17 [17%]), and anaemia (28 [27%]; 16 [16%]; and 19 [19%]). Serious adverse events occurred in 53 (51%) patients in the ramucirumab group, 56 (55%) in the merestinib group, and 48 (48%) in the pooled placebo group. Treatment-related deaths (deemed related by the investigator) occurred in one (1%) of 104 patients in the ramucirumab group (cardiac arrest) and two (2%) of 102 patients in the merestinib group (pulmonary embolism [n=1] and sepsis [n=1]). INTERPRETATION: Adding ramucirumab or merestinib to first-line cisplatin-gemcitabine was well tolerated, with no new safety signals, but neither improved progression-free survival in patients with molecularly unselected, locally advanced or metastatic biliary tract cancer. The role of these targeted inhibitors remains investigational, highlighting the need for further understanding of biliary tract malignancies and the contribution of molecular selection. FUNDING: Eli Lilly and Company.

Isolation and purification of flavonoids from Euonymus alatus by high-speed countercurrent chromatography and neuroprotective effect of rhamnazin-3-O-rutinoside in vitro.

The flavonoids from Euonymus alatus exhibit many biological activities including significant antioxidant, anti-inflammatory, anti-cancer. In this work, a high-speed countercurrent chromatography method for the isolation and purification of flavonoids from crude extracts of Euonymus alatus was established. The effects of several solvent systems on the separation efficiency of target compounds in the extract of Euonymus alatus were studied. The solvent system composed of n-hexane-ethyl acetate-methanol-water at a volume ratio of (3:5:3:5, v/v) was chosen, in which the lower phase was used as the mobile phase at the rotation speed of 800 rpm and flow rate of 2.0 mL/min. The three flavonoids were obtained and identified as patuletin-3-O-rutinoside, rhamnazin-3-O-rutinoside, and dehydrodicatechin A by mass spectroscopy and nuclear magnetic resonance, and the quantities of patuletin-3-O-rutinoside, rhamnazin-3-O-rutinoside, and dehydrodicatechin A were 2.2, 9.7, and 1.8 mg, respectively. The results indicated that high-speed countercurrent chromatography was a simple and efficient method for the isolation and purification of flavonoids from the crude extracts of Euonymus alatus. The cellular antioxidant activity experimental result indicated that rhamnazin-3-O-rutinoside could alleviate H2 O2 -induced oxidative stress.

Purification of linarin and hesperidin from Mentha haplocalyx by aqueous two-phase flotation coupled with preparative HPLC and evaluation of the neuroprotective effect of linarin.

The volatile oil of Mentha haplocalyx is widely used in medicine, food, and cosmetics. However, a large amount of its residue after steam extraction of volatile oil is abandoned, resulting in a waste of resources. The method of aqueous two-phase flotation coupled with preparative high-performance liquid chromatography was established for the separation and purification of nonvolatile active compounds from Mentha haplocalyx for the first time. The parameters of the two-phase aqueous flotation were optimized. Under the optimal conditions including flotation solvent PEG 1000 aqueous solution (1:1, w/w), pH 5, (NH4 )2 SO4 concentration of 350 g/L in aqueous phase, N2 flow rate of 20 mL/min, and flotation time of 20 min, the flotation efficiency of linarin, hesperidin, and didymin was 82.24, 76.38, and 89.33%, respectively. The linarin and hesperidin with the high purities of 95.8 and 97.2%, respectively, were obtained by using preparative high performance liquid chromatography. The neuroprotective effect of linarin against H2 O2 -induced oxidative stress in rat hippocampal neurons was investigated. The experimental result indicated that linarin could alleviate H2 O2 -induced oxidative stress. The work indicated that the combination of aqueous two-phase flotation and preparative high performance liquid chromatography is a feasible and practical method for the purification of nonvolatile active substances from Mentha haplocalyx, which would provide a reference process for the comprehensive utilization of M. haplocalyx. Especially, linarin might be used as a good source of natural neuroprotectants.

Ginsenoside Re Preserves Cardiac Function and Ameliorates Left Ventricular Remodeling in a Rat Model of Myocardial Infarction.

Ginsenoside Re, an herbal ingredient from ginseng, has been demonstrated to protect the heart from various cardiovascular diseases. In this study, we investigated the protective effects and mechanisms of ginsenoside Re (Gin-Re) on cardiac function and left ventricular remodeling in a rat model of myocardial infarction (MI). After ligating the left anterior descending coronary artery, Wistar rats were treated with Gin-Re (135 mg/kg) by gavage everyday for 4 weeks. Serological detection showed that Gin-Re significantly inhibited myocardial injury and attenuated oxidative stress in MI rats. Echocardiographic observation showed that Gin-Re significantly improved cardiac function and prevented left ventricular dilatation induced by MI. Pathological observation found that Gin-Re significantly decreased interstitial fibrosis in the left ventricle of MI rats. Compared with the MI group, Gin-Re treatment promoted AMPKα phosphorylation, decreased TGF-ß1 expression, and attenuated Smad2/3 activation. After Gin-Re treatment, the phosphorylation of FAK, PI3K p110α, and Akt was enhanced in MI rats, while PI3K p110ß showed no difference compared with the MI group. These results indicate that Gin-Re may improve MI-induced cardiac dysfunction and mitigate ventricular remodeling through regulation of the AMPK/TGF-ß1/Smad2/3 and FAK/PI3K p110α/Akt signaling pathways.

Down-regulation of UBA6 exacerbates brain injury by inhibiting the activation of Notch signaling pathway to promote cerebral cell apoptosis in rat acute cerebral infarction model.

This study aimed to examine the UBA6 role in brain injury mediated by acute cerebral infarction (ACI). In order to screen potential therapeutic targets for ACI, two expression profiles, including GSE97537 and GSE97533 datasets, were downloaded from the GEO database. The Venn method to identify the common DEGs. 68 up-regulated overlapping DEGs and 51 down-regulated overlapping DEGs were used to construct the PPI network by STRING online database. UBA6 was identified as a hub gene by the CytoHubba plugin from Cytoscape. GO and KEGG pathway enrichment analyses were conducted using DAVID online website. UBA6 knockout exacerbated MCAO-mediated brain injury and cell apoptosis in rat brain tissues by H&E and TTC staining and TUNEL assay. The results of flow cytometry and western blot assays further demonstrated that UBA6 inhibition induced the apoptosis of hippocampal neurons and increased cleaved-caspase-3/9 protein levels. Notch1, NICD and Hes1 protein levels were suppressed by down-regulated UBA6. UBA6 was lowly expression in poor prognosis group of 100 patients with ACI. Logistic regression analysis indicated that hypertension, blood glucose, urokinase dose, UBA6 expression and AF were the main risk factors of poor prognosis after thrombolytic therapy for patients with ACI. The ROC curve analysis showed that the sensitivity and specificity of UBA6 was good (sensitivity 100%, specificity 89%, and AUC = 0.772) to be used to evaluate the poor prognosis of ACI. In conclusion, down-regulated UBA6 intensified MCAO-induced brain injury by inhibiting the activation of Notch signaling pathway to promote the apoptosis of hippocampal neurons and was used to predict the poor prognosis of ACI.

Isolation and purification of alkaloids from the fruits of Macleaya cordata by ionic-liquid-modified high-speed counter-current chromatography.

Macleaya cordata (Willd) R. Br. is a medicinal plant. The most important bioactive compounds of M. cordata are alkaloids that have many biological activities including antifungal, anti-inflammatory, and antitumor. In this study, an ionic-liquid-modified high-speed counter-current chromatography method was established to obtain alkaloids from the fruits of M. cordata. The conditions of ionic-liquid-modified high-speed counter-current chromatography, including solvent systems, the content of ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate [C4 mim][BF4 ]), and the posttreatment of the ionic liquid, were investigated. Five alkaloids protopine, allocryptopine, sanguinarine, 8-O-demethylchelerythrine, and chelerythrine were separated from the extract of the fruits using a high speed counter-current chromatography with two-phase solvent system composed of dichloromethane/methanol/0.3 mol/L hydrochloric acid aqueous solution/[C4 mim][BF4 ] (4:2:2:0.015, v/v). Their purities were 96.33, 95.56, 97.94, 96.22, and 97.90%, respectively. The results indicated that a small amount of ionic liquids as modifier of the two-phase solvent system could shorten the separation time and improve the separation efficiency of the alkaloids from the fruits. The ionic-liquid-modified high-speed counter-current chromatography would provide a feasible way for highly effective separation of alkaloids from natural products.

Ginkgetin aglycone attenuates the apoptosis and inflammation response through nuclear factor-kB signaling pathway in ischemic-reperfusion injury.

AIMS: Acute myocardial infarction (AMI) is one of the most threaten disease in the world. Ginkgetin aglycone (GA) was a new kind of Ginkgo biloba, involved in various diseases, including kidney injury and acute pancreatitis. However, the function of GA in AMI remains unknown. The aim of the study was to investigate the characteristics and function of GA in ischemic-reperfusion injury. METHODS: H2 O 2 - and CoCl 2 -treated H9C2 cells were used to analyze the function of GA in vitro. Caspase 3, interleukin-6 (IL-6), and tumor necrosis factor-α were detected to evaluate the apoptosis and inflammation response. Rat AMI was performed to elucidate the function in vivo. RESULTS: We found that GA could reduce the apoptosis and improved cell survival of H2 O 2 -treated H9C2 cardiomyocytes and CoCl 2 -treated H9C2 cells. GA attenuated CoCl 2 -induced inflammatory response and the level of cleaved caspase 33, suggesting that GA could alleviate the cell apoptosis. GA improved the cardiac function and attenuated the inflammatory cell infiltration in vivo. We also found that nuclear factor-kB signaling pathway, which was activated under hypoxia environment, was also suppressed in the GA-treated group. CONCLUSION: We verified the function and mechanism of GA and provide evidence that GA may play a vital role in ischemic-reperfusion injury, and understanding the precise role of GA will undoubtedly shed new light on the clinical treatment.

Rs531564 polymorphism in microRNA-214 regulates interleukin-6R expression in anal fissure patients to affect the risk of anal abscess formation.

BACKGROUND: Anal abscess is an important complication of anal fissure (AF), whereas interleukin-6R (IL-6R) has been implicated in the development of abscess. In this study, we aimed to explore the possible molecular mechanisms underlying the regulatory effects of miRNAs on IL-6R and other inflammatory factors related to the induction of anal abscess in AF. METHODS: Bioinformatics analysis, luciferase assay, real-time polymerase chain reaction, and Western blot analysis were performed to identify the possible regulatory relationships between IL-6R and miR-124/miR-125a by comparing the differentiated expression of miR-125a, miR-124, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and IL-4 among different groups of AF patients. RESULTS: IL-6R messenger RNA (mRNA) was identified as a target gene of miR-124 because the luciferase activity in cells cotransfected with wild-type IL-6R and miR-124 mimics was significantly reduced. In addition, the expression of IL-6R mRNA and protein was significantly inhibited in the presence of miR-124 or an IL-6R inhibitor, confirming the presence of a negative regulatory relationship between miR-124 and IL-6R. Moreover, miR-124 and inflammatory factors were differentially expressed in AF patients carrying different genotypes of rs531564 polymorphism. CONCLUSIONS: miR-124 and inflammatory factors TNF-α, IFN-γ, and IL-4 may be used as indicators of anal abscess development in AF patients. In addition, miR-124 polymorphism rs531564 is involved with the pathogenesis of anal abscess in AF patients, and the presence of rs531564 may increase the incidence of anal abscess via upregulating the expression of IL-6R, TNF-α, IFN-γ, and IL-4.

Panax Quinquefolium Saponins Attenuate Myocardial Dysfunction Induced by Chronic Ischemia.

BACKGROUND/AIMS: Previous studies in rat models of myocardial ischemia showed that Panax quinquefolium saponins (PQS) could attenuate ischemic/reperfusion injury, increase vessel density and improve cardiac function. In the current study, we examined whether PQS could attenuate myocardial dysfunction in a swine model of chronic myocardial ischemia (CMI). METHODS: CMI was established in Bama mini-pigs by placing amroid constrictor on the left anterior descending artery (LAD). Starting from 2 months after the surgery, pigs randomly received PQS (30 mg/kg/day), atorvastatin (1.5 mg/kg/day), or no drug for one month (n=6). A group of pigs receiving sham surgery was included as an additional control. Glucose utilization was assessed with positron emission tomography-computer tomography (PET-CT). Cardiac function was assessed with echocardiography. Myocyte size, nuclear density, and arteriolar density were examined in tissue section obtained from the ischemia area. Potential molecular targets of PQS were identified using proteomic analysis with isobaric tags for relative and absolute quantitation (iTARQ) and network pharmacology. RESULTS: In comparison to the sham controls, pigs implanted with ameroid constrictor had decreased ventricular wall motion, left ventricular ejection fraction (LVEF), and glucose utilization. PQS significantly increased cardiac function and glucose utilization. Arteriole density and myocyte nuclear density were increased. Myocyte diameter was decreased. PQS also attenuated the CMI-induced change of protein expression profile. The effects of atorvastatin were generally similar to that of PQS. However, PQS attenuated the reduction of left ventricular systolic WT induced by CMI more robustly than atorvastatin. CONCLUSION: The results from the current study supports the use of PQS in patients with coronary artery disease.

Decreased domain size of p-DTS(FBTTh2)2/P(NDI2OD-T2) blend films due to their different solution aggregation behavior at different temperatures.

Nanoscale interpenetrating networks play a key role in determining the optoelectrical properties of functional blends. However, phase separated large domain sizes could probably be observed in pristine films composed of two crystalline components. For example, p-DTS(FBTTh2)2/P(NDI2OD-T2) 3/2 blend films with interpenetrating networks are obtained, however, large domain sizes are found when they are prepared from a 20 °C solution due to the simultaneous process of crystallization and phase separation during solvent evaporation. In this paper, we proposed to reduce the domain size of p-DTS(FBTTh2)2/P(NDI2OD-T2) blend films using their different solution aggregation behaviors at different temperatures. The aggregation of p-DTS(FBTTh2)2 molecules in chlorobenzene (CB) was insensitive to the solution temperature. However, the in situ absorption spectra of the neat P(NDI2OD-T2) solution from 80 °C to room temperature indicated that P(NDI2OD-T2) aggregation increased with decreasing temperature due to intrachain interactions. Therefore, in order to reduce the domain size, we employed a hot solution to prepare the blend films. During the solidification process, the majority of p-DTS(FBTTh2)2 molecules were confined in the P(NDI2OD-T2) networks prior to occurrence of severe p-DTS(FBTTh2)2 aggregation. Thus, the domain size of the p-DTS(FBTTh2)2 phase became smaller than that of the pristine films, leading to a decrease in the corresponding photoluminescence intensity of the blend films. In addition, the crystallinity of the blend films improved after thermal annealing, which resulted from the ordered alignment of p-DTS(FBTTh2)2 molecules facilitated by their enhanced diffusion ability. Based on the various morphologies, a possible phase diagram of the p-DTS(FBTTh2)2/P(NDI2OD-T2) blend system was depicted, which could be a guide to directly control the morphology of blend films.