The correlation between time-intensity curve parameters of transrectal contrast-enhanced ultrasound and pathological prognostic factors in rectal adenocarcinoma.

AIMS: To investigate the correlation between time-intensity curve (TIC) parameters obtained from transrectal contrast-enhanced ultrasound (TR-CEUS) and important pathological prognostic factors in rectal adenocarcinoma. MATERIAL AND METHODS:  We retrospectively included 477 patients with pathologically confirmed rectal adenocarcinoma. TIC parameters were derived from preoperative dynamic TR-CEUS images. These parameters included peak intensity (PI), time to peak (TTP),mean transit time (MTT), slope (S), and area under the curve (AREA). Pathological prognostic factors included TN stage, tumor diameter, lymphovascular invasion (LVI), perineural invasion, and tumor differentiation. Spearman's correlation analysis and binary logistic regression were used to analyze the association between TIC parameters and pathological prognostic factors. RESULTS: pT1-2 stages rectal carcinomas exhibited higher PI-max, PI-min, S-max, S-min, AREA-max, and AREA-min than pT3-4 stages (all p<0.05). pN0 stage rectal adenocarcinomas displayed higher PI-max, S-max, AREA-max, PI-ratio, Sratio, and AREA-ratio than pN1-2 stage (all p<0.05). PI-ratio and S-ratio were higher in the LVI-negative and tumor diameter ≥4cm group compared to the LVI-positive and tumor diameter <4cm group, respectively (p<0.05). Well-differentiated rectal adenocarcinomas displayed higher PI-max, AREA-max, PI-ratio, S-ratio, and AREA-ratio than the moderate-poor differentiated group (all p<0.05). PI-max, S-max, AREA-max, PI-ratio, S-ratio, and AREA-ratio were negatively correlated with pN stage (all p<0.05). PI-ratio and S-ratio were independent predictive factors for the pN stage (OR=0.774, OR=1.048). S-ratio and AREA-ratio were independent predictive factors for tumor differentiation (OR=1.071, OR=0.911). CONCLUSIONS: TIC parameters derived from TR-CEUS exhibit correlations with specific pathological prognostic factors in rectal adenocarcinomas. This non-invasive method may hold promise for preoperatively assessing the prognosis of rectal adenocarcinoma patients.

Assessment of the Effects of Sphingosine Kinase 1/Sphingosine-1-Phosphate on Microangiogenesis at Rat Myofascial Trigger Points Using Contrast-Enhanced Ultrasonography.

Purpose: Few studies have assessed the effects of sphingosine kinase 1/sphingosine-1-phosphate (SPHK1/S1P) on microangiogenesis at rat myofascial trigger points (MTrPs) using contrast-enhanced ultrasonography (CEUS). This study aimed to address these deficiencies. Here, we investigated the effects of SPHK1/S1P on MTrP microangiogenesis and the value of CEUS in evaluating these effects. Methods: Forty Sprague‒Dawley rats were subdivided into two groups: control and MTrP groups. MTrPs were established by 8 weeks of the strike procedure combined with eccentric motion and 4 weeks of recovery. All rats were euthanized after having undergone CEUS with an overdose of pentobarbital sodium. MTrP and control tissue samples were removed for haematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) imaging. The tissue was dehydrated, cleared, and embedded before sectioning. The sections were then incubated overnight at 4°C, and immunohistochemistry was carried out with primary antibodies including rabbit anti-CD31, rabbit anti-SPHK1and rabbit anti-S1PR1. Results: MTrP rats exhibited spontaneous electrical activity (SEA) and a local twitch response (LTR) during electromyography (EMG) examination. The CEUS time-intensity curves (TICs) showed that the perfusion intensity in the MTrPs and surrounding tissue area was increased, with faster perfusion than in normal sites, while the TICs in the control group slowly increased and then slowly decreased. The correlation coefficient between the microvessel density (MVD) and sphingosine 1-phosphate receptor 1 (S1PR1) was 0.716 (p <0.01). Spearman correlation analysis revealed that Spearman's rho (ρ) values between the MVD and peak intensity (PI), between the MVD and area under the curve (AUC), and between the MVD and SPHK1 were > 0.5 (p <0.05), > 0.7 (p <0.01), and > 0.7 (p <0.01), respectively. Conclusion: CEUS is valuable for detecting microangiogenesis within MTrPs, and SPHK1/S1P plays an important role in promoting MTrP tissue microangiogenesis.

Contrast Enhanced Ultrasonography of Kidney in Chronic Intermittent Hypoxia Rat Model.

OBJECTIVES: The objective of our study was to assess the ability of contrast-enhanced ultrasound (CEUS) in evaluating renal microperfusion in an animal model. METHODS: Twenty Sprague-Dawley rats were subdivided into two groups: the normal and chronic intermittent hypoxia (CIH) groups. In the CIH model, 10 Sprague-Dawley rats were exposed to CIH for 8 weeks to mimic obstructive sleep apnea (OSA). The CEUS parameters of the renal cortex and medulla were obtained and compared between groups. The pathological changes of the kidney tissues were examined by histological staining such as hematoxylin and eosin (H&E) and Masson's trichrome. RESULTS: CIH caused morphological damage to kidneys. In the cortex, the peak intensity (PI) (P = .009) was significantly lower and time to peak (Ttop) (P = .019) was significantly prolonged in the CIH group compared with the controls. The area under ascending curve (WiAUC) in the medulla and cortex were both significantly lower in the CIH group than those in the control group (P both <.05). CEUS parameters (including PI and WiAUC of the cortex and WiAUC of the medulla) were negatively correlated with serum creatinine (P all <.05). In the medulla, the area under descending curve (WoAUC) was positively correlated with serum creatinine (P = .027), PI was negatively correlated with uric acid (P = .034). CONCLUSION: CEUS parameters (including Ttop, PI, WoAUC, and WiAUC) reflect renal microvascular changes in CIH. CEUS could be a safe and accurate imaging method to assess renal microvascular damage in CIH rats.

Ion-based high-order harmonic generation from water window to keV region with a transverse disruptive pulse for quasi-phase-matching.

A scheme for ion-based high-harmonic generation from water window to keV x-ray is investigated. He1+ ions with 54.42-eV ionization potential extend the harmonic cutoff energy to 1 keV. The transverse selective-zoning method of quasi-phase-matching is utilized to overcome the severe plasma dispersion in a highly ionized medium. The calculated conversion efficiency reaches about 15% of the perfect phase-matching condition. Wavelength tunability is achieved by incorporating a programmable spatial-light modulator to control the quasi-phase-matching pattern.

The Protective Effects of Sulforaphane on High-Fat Diet-Induced Obesity in Mice Through Browning of White Fat.

Background: Sulforaphane (SFN), an isothiocyanate naturally occurring in cruciferous vegetables, is a potent indirect antioxidant and a promising agent for the control of metabolic disorder disease. The glucose intolerance and adipogenesis induced by diet in rats was inhibited by SFN. Strategies aimed at induction of brown adipose tissue (BAT) could be a potentially useful way to against obesity. However, in vivo protective effect of SFN against obesity by browning white adipocyte has not been reported. Our present study is aimed at evaluation the efficacy of the SFN against the high-fat induced-obesity mice and investigating the potential mechanism. Methods: High-Fat Diet-induced obese female C57BL/6 mice were intraperitoneally injected with SFN (10 mg/kg) daily. Body weight was recorded every 3 days. 30 days later, glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed. At the end of experiment, fat mass were measured and the adipogenesis as well as browning associated genes expression in white adipose tissue (WAT) were determined by RT-qPCR and western blot. Histological examination of the adipose tissue samples were carried out with hematoxylin-eosin (HE) staining and immunofluorescence staining method. In vitro, pre-adipocytes C3H10T1/2 were treated with SFN to investigate the direct effects on adipogenesis. Results: SFN suppressed HFD-induced body weight gain and reduced the size of fat cells in mice. SFN suppressed the expression of key genes in adipogenesis, inhibited lipid accumulation in C3H10T1/2 cells, increased the expression of brown adipocyte-specific markers and mitochondrial biogenesis in vivo and in vitro, and decreased cellular and mitochondrial oxidative stress. These results suggested that SFN, as a nutritional factor, has great potential role in the battle against obesity by inducing the browning of white fat. Conclusion: SFN could significantly decrease the fat mass, and improve glucose metabolism and increase insulin sensitivity of HFD-induced obese mice by promoting the browning of white fat and enhancing the mitochondrial biogenesis in WAT. Our study proves that SFN could serve as a potential medicine in anti-obesity and related diseases.

Sulforaphane Inhibits Osteoclastogenesis via Suppression of the Autophagic Pathway.

Previous studies have demonstrated that sulforaphane (SFN) is a promising agent against osteoclastic bone destruction. However, the mechanism underlying its anti-osteoclastogenic activity is still unclear. Herein, for the first time, we explored the potential role of autophagy in SFN-mediated anti-osteoclastogenesis in vitro and in vivo. We established an osteoclastogenesis model using receptor activator of nuclear factor kappa-ß ligand (RANKL)-induced RAW264.7 cells and bone marrow macrophages (BMMs). Tartrate-resistant acid phosphatase (TRAP) staining showed the formation of osteoclasts. We observed autophagosomes by transmission electron microscopy (TEM). In vitro, we found that SFN inhibited osteoclastogenesis (number of osteoclasts: 22.67 ± 0.88 in the SFN (0) group vs. 20.33 ± 1.45 in the SFN (1 µM) group vs. 13.00 ± 1.00 in the SFN (2.5 µM) group vs. 6.66 ± 1.20 in the SFN (2.5 µM) group), decreased the number of autophagosomes, and suppressed the accumulation of several autophagic proteins in osteoclast precursors. The activation of autophagy by rapamycin (RAP) almost reversed the SFN-elicited anti-osteoclastogenesis (number of osteoclasts: 22.67 ± 0.88 in the control group vs. 13.00 ± 1.00 in the SFN group vs. 17.33 ± 0.33 in the SFN+RAP group). Furthermore, Western blot (WB) analysis revealed that SFN inhibited the phosphorylation of c-Jun N-terminal kinase (JNK). The JNK activator anisomycin significantly promoted autophagy, whereas the inhibitor SP600125 markedly suppressed autophagic activation in pre-osteoclasts. Microcomputed tomography (CT), immunohistochemistry (IHC), and immunofluorescence (IF) were used to analyze the results in vivo. Consistent with the in vitro results, we found that the administration of SFN could decrease the number of osteoclasts and the expression of autophagic light chain 3 (LC3) and protect against lipopolysaccharide (LPS)-induced calvarial erosion. Our findings highlight autophagy as a crucial mechanism of SFN-mediated anti-osteoclastogenesis and show that the JNK signaling pathway participates in this process.

Sonographic Assessment of Oropharynx Movement During Deep Breathing.

To investigate the feasibility of ultrasonography in detecting the oropharynx movement during deep breathing and to quantitatively analyze oropharynx airway lumen changes during deep breathing. The motions of oropharynx were monitored, and sonographic measurements of airway lumen were obtained during deep breathing in 448 healthy volunteers. Adequate visualization of oropharynx movement was obtained on all healthy volunteers. The anterior-posterior (AP) diameters and AP/transverse (T) diameter ratios were greater at the end of deep inspiration than that at the end of deep expiration for each sex (p < 0.01). The anterior-posterior dimensional changes were greater than lateral airway dimensional changes each sex (p < 0.05). Ultrasonography could provide realistic impression of the process on the oropharynx movement during deep breathing and perform the quantitative analysis of the oropharynx airway lumen changes during deep breathing. The results were encouraging and supported the utility of ultrasonography in future studies.

Contrast-enhanced Ultrasound in evaluating of angiogenesis and tumor staging of nasopharyngeal carcinoma in nude mice.

OBJECTIVE: To explore the use of Contrast-enhanced Ultrasound (CEUS) in evaluating angiogenesis in a xenograft nasopharyngeal carcinoma (NPC) model in nude mice and the evolution of CEUS parameters according to the growth of NPC. METHODS: Nude mice were divided into three groups according to experiments conducted at various times from tumor implantation (8 mice/group; group A: 4 weeks from implantation; group B:6 weeks from implantation; group C:8 weeks from implantation). CNE-2 cells were transplanted in 24 nude mice and CEUS evaluations of the tumors were performed at 4, 6 or 8 weeks from implantation. CEUS parametric perfusion images and pathological findings were recorded. R version 3.4.4 software was used to analyze the CEUS parameters and pathological findings. RESULTS: One-way anova analysis indicated statistically significant differences among the three groups with the parameters of peak intensity (PI) (p<0.001), area wash in (AWI) (p<0.001), area wash out (AWO) (p<0.001) and tumor volumes (p<0.001).Pearson correlation coefficient analysis indicated that microvessel density (MVD) was correlated with tumor volume (r = 0.644, p = 0.001), PI (r = 0.904, p<0.0001), AWI (r = 0.547, p = 0.008) and AWO (r = 0.744, P<0.0001). Tumor volume was correlated with MVD (r = 0.644, p = 0.001), PI (r = 0.625, p = 0.002), AWI (r = 0.528, p = 0.012) and AWO (r = 0.784, p<0.001). The percentage of necrosis in histological sections was correlated with the percentage of CEUS unperfused area (r = 0.446,p = 0.038). Spearman rank correlation coefficient analysis indicated that vascular endothelial growth factor (VEGF) was correlated with PI (r = 0.462, P = 0.032). Welch t test indicated PI, AWI and AWO parameters were significantly lower than that of kidneys (p<0.001, p = 0.009, p = 0.005). CONCLUSIONS: The CEUS parameters PI, AWI and AWO indirectly reflect the MVD and the tumor volume in our model of subcutaneous transplanted NPC in nude mice, providing precious information on angiogenesis and tumor growth. VEGF may play a role in promoting angiogenesis of NPC.

MG53 Inhibits the Progression of Tongue Cancer Cells through Regulating PI3K-AKT Signaling Pathway: Evidence from 3D Cell Culture and Animal Model.

MG53 is transcriptionally activated by the IRS-1/PI3K/AKT signal pathway, which is closely related with oncogenesis of several tumors. Here, the role of MG53 in the tumorigenesis of tongue cancer is analyzed in vitro and in vivo. The stable MG53 overexpression/knockdown SCC9 and SCC25 cells are constructed through retrovirus infection. Then a PLGA cylinder is used to provide a 3D culture environment for cell growth. Cell counting results suggest that overexpression of MG53 inhibits the cell proliferation and colony formation of SCC9 and SCC25 cells. While knockdown of MG53 has the opposite effect. Furthermore, knockdown of MG53 significantly promotes the invasion of SCC9 and SCC25 cells. Western blotting data confirm that MG53 affects the expression of the AKT signaling pathway. In a xenograft assay, knockdown of MG53 promotes the growth of xenograft which is induced by SCC25 cells in nude mice. The findings demonstrate that MG53 affects the biological behavior of human tongue cancer SCC9 and SCC25 cells.

Investigation of the Upper Airway Anatomy With Ultrasound.

OBJECTIVE: The aims of this study were to describe the relationship between the scanning planes and appearance of the upper airway on sonography and to demonstrate the reliability and reproducibility of sonographic measurements of the upper airway. METHODS: Airway sonoanatomy was recognized by comparing the airway images and the corresponding cadaver's anatomical specimens. Systemic sonographic examination of 267 healthy volunteers was conducted to obtain the sonographic measurement of airway lumen. The reliability and reproducibility studies were conducted in 40 healthy volunteers. RESULT: The air-filled upper airway appeared as a bright heterogeneous hyperechoic line. During deep inspiration, the upper airway lumen expanded to the highest anterior-posterior dimension, whereas during deep expiration, the lateral dimension tended to increase. The sonographic measurements had good reproducibility, with intraclass correlation coefficient ranging from 0.722 to 0.887 and 0.727 to 0.882 for interobserver and intraobserver reliability, respectively. CONCLUSIONS: Ultrasonography can determine the anatomy of the upper airway and perform the quantitative analysis of the upper airway lumen during respiration. The results were encouraging and support the utility of ultrasonography in future airway disorder studies.

Retraction Notice: 3D DWT-DCT and Logistic MAP Based Robust Watermarking for Medical Volume Data.

[This retracts the article on p. 131 in vol. 8.].

3D DWT-DCT and Logistic MAP Based Robust Watermarking for Medical Volume Data.

Applying digital watermarking technique for the security protection of medical information systems is a hotspot of research in recent years. In this paper, we present a robust watermarking algorithm for medical volume data using 3D DWT-DCT and Logistic Map. After applying Logistic Map to enhance the security of watermarking, the visual feature vector of medical volume data is obtained using 3D DWT-DCT. Combining the feature vector, the third party concept and Hash function, a zero-watermarking scheme can be achieved. The proposed algorithm can mitigate the illogicality between robustness and invisibility. The experiment results show that the proposed algorithm is robust to common and geometrical attacks.

[Effect of method of soothing liver and regulating qi on expression of gastrin and somatostatin in hypothalamus, castric antrum of functional dyspepsia rats].

OBJECTIVE: To explore the effects of the method of soothing the liver and regulating qi on expression of gastrin and somatostatin in hypothalamus and gastric antrum of functional dyspepsia model rats. METHOD: The 32 rats were randomly divided into normal group, model group, Chaihu Shugansan group and domperidone group (n = 8). The functional dyspepsia model was established by constantly squeezing their tails and mean while saline, Chaihu Shugansan decoction and domperidone suspension were administered respectively to 4 groups by gavage. The expression of gastrin and somatostatin in hypothalamus and gastric antrum of rats by immunohistochemical were detected 3 weeks later. RESULT: The expression of GAS in the hypothalamus and gastric antrum of model group were less than those of normal group (P < 0.05, P < 0.01), while the expression of SS in the hypothalamus and gastric antrum in Model group were significantly increased than those of normal group (P < 0.01). The expression of GAS and SS in gastric antrum of Chaihu Shugansan group and domperidone group were increased and decreased respectively, and the differences were significant (P < 0.05, P < 0.01). There were no obvious difference about expression of GAS, SS in the hypothalamus between domperidone group and model group. GAS expression in hypothalamus of Chaihu Shugansan group were increased than those of normal group but there was no obvious difference in SS expression in hypothalamus between Chaihu Shugansan group and model group. CONCLUSION: The method of soothing the liver and regulating qi can increase GAS expression in central and peripheral and decrease SS expression in peripheral gastric antrum, which may be one of its therapeutic mechanisms on functional dyspepsia.