Correlation of MRI quantitative perfusion parameters with EGFR, VEGF and EGFR gene mutations in non-small cell cancer.

To explore the relationship between quantitative perfusion histogram parameters of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with the expression of tumor tissue epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) and EGFR gene mutations in non-small cell lung cancer (NSCLC). A total of 44 consecutive patients with known NSCLC were recruited from March 2018 to August 2021. Histogram parameters (mean, uniformity, skewness, energy, kurtosis, entropy, percentile) of each (Ktrans, Kep, Ve, Vp, Fp) were obtained by Omni Kinetics software. Immunohistochemistry staining was used in the detection of the expression of VEGF and EGFR protein, and the mutation of EGFR gene was detected by PCR. Corresponding statistical test was performed to compare the parameters and protein expression between squamous cell carcinoma (SCC) and adenocarcinoma (AC), as well as EGFR mutations and wild-type. Correlation analysis was used to evaluate the correlation between parameters with the expression of VEGF and EGFR protein. Fp (skewness, kurtosis, energy) were statistically significant between SCC and AC, and the area under the ROC curve were 0.733, 0.700 and 0.675, respectively. The expression of VEGF in AC was higher than in SCC. Fp (skewness, kurtosis, energy) were negatively correlated with VEGF (r = - 0.527, - 0.428, - 0.342); Ktrans (Q50) was positively correlated with VEGF (r = 0.32); Kep (energy), Ktrans (skewness, kurtosis) were positively correlated with EGFR (r = 0.622, r = 0.375, 0.358), some histogram parameters of Kep, Ktrans (uniformity, entropy) and Ve (kurtosis) were negatively correlated with EGFR (r = - 0.312 to - 0.644). Some perfusion histogram parameters were statistically significant between EGFR mutations and wild-type, they were higher in wild-type than mutated (P < 0.05). Quantitative perfusion histogram parameters of DCE-MRI have a certain value in the differential diagnosis of NSCLC, which have the potential to non-invasively evaluate the expression of cell signaling pathway-related protein.

Characteristics and Influencing Factors of Coagulation Dysfunction Caused by Cefoperazone/Sulbactam.

Objective: To evaluate associations between patient characteristics and cefoperazone/sulbactam-associated coagulation dysfunction. Methods: Retrospective analysis was performed on 821 cases of bacterial infection treated with cefoperazone/sulbactam for more than three days in the Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, from January 2018 to June 2022. The patients were divided into normal coagulation function group (NCFG) (781 cases) and abnormal coagulation function group (ACFG) (40 cases) according to their coagulation function. Univariate and multivariate logistic regression analysis used the general data of the two groups of patients to investigate the risk factors of abnormal coagulation function caused by cefoperazone/sulbactam. Results: The incidence of abnormal coagulation function caused by cefoperazone/sulbactam was 4.87% (40/821). There was no significant difference in gender, body mass index (BMI), marriage, educational background, and concurrent medical conditions between the two groups (all P > .05). The patients in ACFG were older, the dosage and duration of cefoperazone/sulbactam were more prolonged, and the liver and kidney functions were more abnormal than those in NCFG, with significant differences (all P < .05). Univariate and multivariate logistic regression analysis showed that age (≥ 65 years old) (OR=1.293, 95%CI:0.897-1.287), duration of therapy (>10d) (OR=1.765, 95%CI:1.052-3.761), daily dosage (>6g) (OR=3.291, 95%CI:1.732-6.871), aspartate aminotransferase (AST) (≥ 23.98U/L) (OR=3.281, 95%CI:1.009-6.981), alanine aminotransferase (ALT) (≥ 24.03U/L) (OR=2.109, 95%CI:1.276-3.298), and serum creatinine (SCR) (>107 µ mol/L) (OR=2.716, 95%CI:1.023-4.398), prothrombin time (PT) (≥ 13.9U/L) (OR=1.571, 95%CI:1.287-1.945) were the risk factors (P < .05). Conclusion: Elderly patients, time of use, daily dose of use, liver and kidney function, and PT are the risk factors of cefoperazone/sulbactam leading to abnormal coagulation function.

Huangshan Floral Mushroom Polysaccharide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Th17/Treg Balance in a Gut Microbiota-Dependent Manner.

SCOPE: Ulcerative colitis (UC) is a common chronic recurrent inflammatory bowel disease. This study attempts to reveal the improvement mechanism of floral mushroom polysaccharide (FMPS) on UC from the perspective of coordinated interaction between intestinal microbes and intestinal helper T cell 17 (Th17)/regulatory T cell (Treg) balance. METHODS AND RESULTS: Dextran sulfate sodium (DSS)-induced colitis mice model is used for the experiment. The results suggest that FMPS up-regulated the expression of occludin, ZO-1, and MUC2, and down-regulated the secretion of TNF-α, IL-1ß, and IL-6 in colitis mice. Importantly, FMPS restores intestinal Th17/Treg balance. Meanwhile, FMPS can regulate intestinal microorganisms and improve the level of short-chain fatty acids (SCFAs) in colitis mice. Intestinal microbial depletion and fecal microbiota transplantation (FMT) experiments reveal that FMPS ameliorated UC is mediated by intestinal microbiome. Flow cytometry further proves that FMPS restores intestinal Th17/Treg balance in a microbial-dependent manner. CONCLUSION: These results indicate that FMPS has the potential to improve UC, and its mechanism depends on the restoration of Th17/Treg balance mediated by intestinal microorganisms. Therefore, it is suggested that FMPS dietary supplement can be potentially used to intervene UC.

Effects of ultrasonic on structure, chain conformation and morphology of pectin extracted from Premna microphylla Turcz.

In this study, ultrasonic effects on structure, chain conformation and morphology of pectin extracted from Premna microphylla Turcz (PEP) and its probable mechanism were investigated. In the process of ultrasonic treatments, the chains of PEP were fractured rapidly within the initial 10 min and then the degradation rate gradually slowed down. The primary structure of PEP nearly remained unchanged after ultrasonic degradation. The rigid semi-flexible chains of PEP were converted into flexible chains, flexible coils, even compact coils. Sonication at low intensity for short time made PEP molecular chains curly collapse and tighten up. Long duration sonication at high intensity generated excessive small rigidness segments that mutually aggregated because of hydrogen bonds and inhibited the self-coiling of PEP chains. Atomic force microscopy (AFM) analysis supported the conformation transition of PEP chains. The results provided a fundamental basis for orientation design and process control of PEP structure.

Ultrasonic effects on molecular weight degradation, physicochemical and rheological properties of pectin extracted from Premna microphylla Turcz.

The high molecular weight and poor solubility of pectin extracted from Premna microphylla Turcz (PEP) limits its application. Therefore, in this paper, the degradation effects of PEP under ultrasound irradiation and the influences of ultrasonic on the PEP processing characteristics were investigated. The results indicated that the Mw of PEP decreased significantly with a narrow distribution after ultrasonic treatment. The degradation kinetics of PEP at different ultrasound intensities were sufficiently described by the 2nd-order kinetics eq. X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis suggested that ultrasonic treatment destroyed the ordered structure inside the PEP, resulting in a looser microscopic morphology. Compared with the control, the thermal stability of PEP was significantly boosted after ultrasonic treatment. Rheological analysis illustrated that the sonicated PEP presented lower apparent viscosities than the original PEP. While the elasticity and thermal reversibility of the degraded products was enhanced. Ultrasonic treatment prominently weakened its shear thinning fluid behavior and thixotropy, thus improved its processing quality. Therefore, desirable PEP can be prepared by ultrasonic irradiation. The results can provide a reference for the development and application of PEP.

The interplay between small vessel disease and Parkinson disease pathology: A longitudinal study.

BACKGROUND: Cerebral small vessel disease (SVD) related brain changes have been found associated with various clinical symptoms of Parkinson disease (PD). On the other hand, PD pathology and treatment may also accelerate SVD progression. OBJECTIVE: The aim of this study is to explore the interplay between SVD and PD pathology using longitudinal dataset. METHODS: We screened 66 healthy controls (HCs) and 114 patients from the Parkinson Progression Markers Initiative (PPMI) database. The peak width of skeletonized mean diffusivity (PSMD) was quantified from diffusion tensor images to reflect vascular pathologies at baseline and 24 months follow-up, and dopamine transporter (DAT) imaging data was used to represent the extent of dopaminergic neuronal degeneration at the same point time. We compared the PSMD between PD patients and HCs, and analyzed whether PSMD and DAT availability could predict each other's progression using multiple regression analyses in PD patients. RESULTS: PSMD at baseline had no significant difference between the HCs and patients with PD (P = 0.169). Higher baseline PSMD was associated with less DAT reduction in the caudate (ß = 0.216, P = 0.029), but not the putamen (ß = 0.058, P = 0.552) in PD patients. Baseline caudate and putamen DAT availability had no significant association with PSMD progression (ß = -0.006, P = 0.950; ß = 0.017, P = 0.860, respectively). CONCLUSIONS: Mild SVD might slow down PD pathology progression, while the effect of PD pathology on the progression of SVD was not significant.

Structural characterization and anti-inflammatory activity of a pectin polysaccharide HBHP-3 from Houttuynia cordata.

In this study, a hot buffer soluble Houttuynia cordata polysaccharide (HBHP-3) with a molecular weight of 397.4 kDa was isolated from H. cordata. HBHP-3 was composed of rhamnose, arabinose, glucose, galactose and galacturonic acid with molar ratio of 16.0:12.6:4.6:18.1:15.6. Structural analysis showed that the main chain of HBHP-3 was composed of →2)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→ and →4)-ß-D-Galp-(1→. There were branched chains of α-L-Araf-(1→, →5)-α-L-Araf-(1→, →4)-α-D-Glcp-(1→, →6)-ß-D-Galp-(1→, ß-D-Galp-(1→ connected to the O-4 positions of →2)-α-L-Rhap-(1→. HBHP-3 effectively inhibited the secretion of NO and the mRNA expression of pro-inflammatory cytokines in a dose-dependent manner in macrophages. HBHP-3 inhibited the phosphorylation of p65 and IκBα proteins as well, illustrating that HBHP-3 exerted its anti-inflammatory activity by inhibiting the activation of NF-κB pathway.

Imaging Manifestations of Intrahepatic Reactive Lymphoid Hyperplasia: A Case Report and Literature Review.

Reactive lymphoid hyperplasia (RLH) of the liver is a rare benign disease. This article describes a 77-year-old female patient with RLH of the liver. The patient was admitted to the hospital due to atrial fibrillation. A liver tumor was incidentally found during abdominal enhanced CT. Further magnetic resonance imaging (MRI) and PET/CT showed four lesions in the liver. The imaging findings suggested hepatocellular carcinoma (HCC), but it was not consistent that the patient had no history of liver cirrhosis and hepatitis, and a variety of tumor markers were within the normal range. The largest lesion was surgically removed and microscopically diagnosed as RLH of the liver. The pathology included a large number of reactive hyperplastic lymphoid follicles. Immunohistochemical examination showed that the infiltrating lymphocytes were polyclonal. The authors believe that the perinodular enhancement on MRI, the obvious limitation of diffusion on DWI, the insignificant increase of SUVmax on PET-CT delayed phase, and the support of clinical data can help distinguish liver RLH from lymphoma and HCC.

Pulmonary lesions: correlative study of dynamic triple-phase enhanced CT perfusion imaging with tumor angiogenesis and vascular endothelial growth factor expression.

BACKGROUND: To investigate value of the quantitative perfusion parameters of dynamic triple-phase enhanced CT in differential diagnosis of pulmonary lesions, and explore the correlation between perfusion parameters of lung cancer with microvessel density (MVD) and vascular endothelial growth factor (VEGF). METHODS: 73 consecutive patients with lung lesions who successfully underwent pre-operative CT perfusion examination with dynamic triple-phase enhanced CT and received a final diagnosis by postoperative pathology or a clinical follow-up. The cases were divided into malignant and benign groups according to the pathological results. CT perfusion parameters, such as Median, Mean, Standard deviation (Std), Q10, Q25, Q50, Q75, Q90 of pulmonary artery perfusion (PAP), bronchial artery perfusion (BAP), perfusion index (PI) and arterial enhancement fraction (AEF) were obtained by performing computed tomography perfusion imaging (CTPI). Computed tomography perfusion (CTP) parameters were compared between malignant and benign lesions. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of CTP parameters in diagnosing malignant lesions. The correlations between CTP parameters with MVD and VEGF were analysed in 36 lung cancer patients who had extra sections be used for immunohistochemistry staining of CD34 and VEGF. RESULTS: BAP (Mean, Std, Q90) and PI Std of benign lesions were higher than malignant lesions (p < 0.05), and PAP (Q10, Q25), PI (Median, Mean, Q10, Q25, Q50) of malignant lesions were higher than the benign (p < 0.05). The area under the ROC curve of PI Mean, PI Q10 and PI Std was 0.722 (95% CI = [0.595-0.845]), 0.728 (95% CI = [0.612-0.844]) and 0.717 (95% CI = [0.598-0.835]) respectively. Partial perfusion parameters of BAP and AEF Q10 were positively correlated with MVD (p value range is < 0.001-0.037, ρ value range is 0.483-0.683), and partial perfusion parameters of PI were negatively correlated with MVD (p value range is 0.001-0.041,ρvalue range is - 0.523-- 0.343). Partial perfusion parameters of BAP and AEF Q10 were positively correlated with VEGF (p value range is 0.001-0.016, ρvalue range is 0.398-0.570), meanwhile some perfusion parameters of PAP and PI were negatively correlated with VEGF (p value range is 0.001-0.040, ρ value range is - 0.657-0.343). CONCLUSIONS: Quantitative parameters of dynamic triple-phase enhanced CT can provide diagnostic basis for the differentiation of lung lesions, and there were connection with tumor angiogenesis and vascular endothelial growth factor expression.

MRI-Based Radiomics Models for Predicting Risk Classification of Gastrointestinal Stromal Tumors.

BACKGROUND: We conduct a study in developing and validating four MRI-based radiomics models to preoperatively predict the risk classification of gastrointestinal stromal tumors (GISTs). METHODS: Forty-one patients (low-risk = 17, intermediate-risk = 13, high-risk = 11) underwent MRI before surgery between September 2013 and March 2019 in this retrospective study. The Kruskal-Wallis test with Bonferonni correction and variance threshold was used to select appropriate features, and the Random Forest model (three classification model) was used to select features among the high-risk, intermediate-risk, and low-risk of GISTs. The predictive performance of the models built by the Random Forest was estimated by a 5-fold cross validation (5FCV). Their performance was estimated using the receiver operating characteristic (ROC) curve, summarized as the area under the ROC curve (AUC). Area under the curve (AUC), accuracy, sensitivity, and specificity for risk classification were reported. Linear discriminant analysis (LDA) was used to assess the discriminative ability of these radiomics models. RESULTS: The high-risk, intermediate-risk, and low-risk of GISTs were well classified by radiomics models, the micro-average of ROC curves was 0.85, 0.81, 0.87 and 0.94 for T1WI, T2WI, ADC and combined three MR sequences. And ROC curves achieved excellent AUCs for T1WI (0.85, 0.75 and 0.82), T2WI (0.69, 0.78 and 0.78), ADC (0.85, 0.77 and 0.80) and combined three MR sequences (0.96, 0.92, 0.81) for the diagnosis of high-risk, intermediate-risk, and low-risk of GISTs, respectively. In addition, LDA demonstrated the different risk of GISTs were correctly classified by radiomics analysis (61.0% for T1WI, 70.7% for T2WI, 83.3% for ADC, and 78.9% for the combined three MR sequences). CONCLUSIONS: Radiomics models based on a single sequence and combined three MR sequences can be a noninvasive method to evaluate the risk classification of GISTs, which may help the treatment of GISTs patients in the future.

Correlation between quantitative perfusion histogram parameters of DCE-MRI and PTEN, P-Akt and m-TOR in different pathological types of lung cancer.

BACKGROUND: To explore if the quantitative perfusion histogram parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlates with the expression of PTEN, P-Akt and m-TOR protein in lung cancer. METHODS: Thirty-three patients with 33 lesions who had been diagnosed with lung cancer were enrolled in this study. They were divided into three groups: squamous cell carcinoma (SCC, 15 cases), adenocarcinoma (AC, 12 cases) and small cell lung cancer (SCLC, 6 cases). Preoperative imaging (conventional imaging and DCE-MRI) was performed on all patients. The Exchange model was used to measure the phar- macokinetic parameters, including Ktrans, Vp, Kep, Ve and Fp, and then the histogram parameters meanvalue, skewness, kurtosis, uniformity, energy, entropy, quantile of above five parameters were analyzed. The expression of PTEN, P-Akt and m-TOR were assessed by immunohistochemistry. Spearman correlation analysis was used to compare the correlation between the quantitative perfusion histogram parameters and the expression of PTEN, P-Akt and m-TOR in different pathological subtypes of lung cancer. RESULTS: The expression of m-TOR (P = 0.013) and P-Akt (P = 0.002) in AC was significantly higher than those in SCC. Vp (uniformity) in SCC group, Ktrans (uniformity), Ve (kurtosis, Q10, Q25) in AC group, Fp (skewness, kurtosis, energy), Ve (Q75, Q90, Q95) in SCLC group was positively correlated with PTEN, and Fp (entropy) in the SCLC group was negatively correlated with PTEN (P < 0.05); Kep (Q5, Q10) in the SCLC group was positively correlated with P-Akt, and Kep (energy) in the SCLC group was negatively correlated with P-Akt (P < 0.05); Kep (Q5) in SCC group and Vp (meanvalue, Q75, Q90, Q95) in SCLC group was positively correlated with m-TOR, and Ve (meanvalue) in SCC group was negatively correlated with m-TOR (P < 0.05). CONCLUSIONS: The quantitative perfusion histogram parameters of DCE-MRI was correlated with the expression of PTEN, P-Akt and m-TOR in different pathological types of lung cancer, which may be used to indirectly evaluate the activation status of PI3K/Akt/mTOR signal pathway gene in lung cancer, and provide important reference for clinical treatment.

An overview on interactions between natural product-derived ß-glucan and small-molecule compounds.

ß-Glucans are widely found in plants and microorganisms, which has a variety of functional activities. During production and application, interactions with other components have a great influence on the structure and functional properties of ß-glucan. In this paper, interactions (including non-covalent interaction and free-radical reaction) between natural product derived ß-glucan and ascorbic acid, polyphenols, bile acids/salts, metal ion or other compounds were summarized. Besides, the mechanism and influence factors of interactions between ß-glucan and small-molecule compounds, and their effects on the functional properties of ß-glucan were detailed. This review aims to develop an understanding and practical suggestions on interactions between ß-glucan and small-molecule compounds, which is expected to provide a useful reference for processing and application.

Ascorbic acid induced degradation of polysaccharide from natural products: a review.

Polysaccharide derived from natural products has a wide range of sources and mild properties, and exhibit various bioactivities. Ascorbic acid is one of the most important nutrients in fruits and vegetables, as well as their products. Ascorbic acid and polysaccharide coexist in many systems during food production and processing. Many studies have found that ascorbic acid at low concentrations degrades polysaccharide derived from natural products via hydroxyl radical. In this paper, the research progress on ascorbic acid induced polysaccharide degradation is summarized from four aspects: mechanism of action, analytical methods, influencing factors and bioactivity of degradation products. It is expected to provide a theoretical basis for further research.

Glutathione S­transferase isozyme alpha 1 is predominantly involved in the cisplatin resistance of common types of solid cancer.

The roles of glutathione S­transferase pi 1 (GSTP1), glutathione S­transferase mu 2 (GSTM2) and glutathione S­transferase alpha 1 (GSTA1) in cisplatin (DDP)­resistance of solid cancer cells (A549/DDP, SKOV3/DDP and SGC7901/DDP) were compared following expression downregulation with small interfering RNAs (siRNAs). DDP cytotoxicity was reflected by its half maximal inhibition concentration (IC50) calculated from data using a Cell Counting Kit­8 assay; cell apoptosis was examined using flow cytometry and Hoechst 33342 staining. Higher activities of GST were detected in the cytosol of DDP­resistant cells, compared with those in the parental DDP­susceptible cells. The silencing efficacy of each positive siRNA was supported by western blot analysis. GSTP1 silencing resulted in a 4­fold sensitization of SGC7901/DDP cells to DDP cytotoxicity, but negligible sensitization of SKOV3/DDP and A549/DDP cells. GSTM2 silencing sensitized SKOV3/DDP and A549/DDP cells to DDP cytotoxicity by ~2­fold, but did not sensitize SGC7901/DDP cells. Notably, GSTA1 silencing enhanced DDP cytotoxicity in SGC7901/DDP cells by 6­fold, in A549/DDP cells by 5­fold and in SKOV3/DDP cells by 2­fold. The combined actions of positive siRNAs and DDP increased the percentages of apoptotic cells in the DDP­resistant solid cancer cells compared with the combined actions of DDP and the negative siRNAs. The present findings indicated that GSTA1 is a predominant GST isozyme associated with DDP resistance of SGC7901/DDP, A549/DDP and SKOV3/DDP cells; GSTA1­specific inhibitors may be general sensitizers of SGC7901/DDP, A549/DDP and SKOV3/DDP cells to DDP cytotoxicity through the promotion of cell apoptosis.

[Optimization and evaluation of an inflammatory cell model in LPS-stimulated PMA-differentiated THP-1 cells].

Objective To develop an optimal inflammatory cell model from lipopolysaccharide (LPS)-stimulated phorbol ester (PMA)-differentiated THP-1 cells, and investigate its response to anti-inflammatory agent phosphodiesterase inhibitor rolipram. Methods THP-1 cells were differentiated by PMA and stimulated by LPS to release inflammatory factors in cell supernatants, like tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), which were detected by ELISA. The doses and durations of both PMA and LPS treatment were optimized to develop the inflammatory cell model. Rolipram was added along with LPS after PMA differentiation to assess the response of cells to the anti-inflammatory agent. Results THP-1 cells showed no significant differences in cell morphology between PMA treatment for 24 hours and for 48 hours, but significantly high levels of TNF-α and IL-6 were released under LPS treatment. TNF-α level increased significantly after the differentiation by PMA at 100 ng/mL in comparison with that at 50 ng/mL, and it increased in a LPS dose-depended manner untill a plateau at 0.2 µg/mL LPS; the secretion level of IL-6 increased remarkably when THP-1 cells were induced by PMA at 100 ng/mL and stimulated by LPS≥1 µg/mL. The inflammatory cell model made using PMA at 100 ng/mL and LPS at 0.5 µg/mL was more sensitive to the anti-inflammatory agent rolipram, compared with that by 0.1 µg/mL LPS. Conclusion PMA at 100 ng/mL was selected for the differentiation of THP-1 cells with the enhanced responsiveness to LPS stimulation; THP-1 cells by the induction of PMA at 100 ng/mL coupled with the stimulation of LPS at no less than 0.2 µg/mL was an optimal inflammatory cell model for significant secretion of TNF-α and IL-6, which was sensitive to the action of anti-inflammatory agents.