ROS-mediated genotoxic stress is involved in NaAsO2-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.

Several epidemiological studies reported that chronic arsenic exposure increased risk of prostate cancer. This study aimed to investigate whether chronic NaAsO2 exposure elevates stemness and chemoresistance in prostate cancer cells. DU145 (wild-type p53) and PC-3 (p53-null) cells were exposed to NaAsO2 (2 µmol/L) for 30 generations. IC50s to docetaxel and cisplatin were increased in NaAsO2-exposed DU145 and PC-3 cells. The number of tumor spheres was elevated in NaAsO2-exposed DU145 and PC-3 cells. Nanog, SOX-2 and ALDH1A1, three markers of cancer stemness, were upregulated in NaAsO2-exposed PC-3 spheres. Moreover, NaAsO2-exposed DU145 and PC-3 cells were arrested in G2/M phase. Histone H2AX phosphorylation on Ser139, an indicator for DNA double-strand break, was upregulated in NaAsO2-exposed DU145 and PC-3 cells. ATM phosphorylation on Ser1981, a key sensor of genotoxic stress, was rapidly elevated in NaAsO2-exposed DU145 cells. Phosphor-p53, a downstream molecule of ATM signaling, and p21, a direct target of p53, were upregulated in NaAsO2-exposed DU145 cells. Unexpectedly, p21 was also elevated in NaAsO2-exposed p53-null PC-3 cells. Antioxidant NAC alleviated NaAsO2-induced ATM phosphorylation, cell cycle arrest, and subsequent stemness enhancement and chemoresistance in both DU145 and PC-3 cells. These results suggest that ROS-mediated genotoxic stress is involved in NaAsO2-induced cell cycle arrest, stemness enhancement and chemoresistance of prostate cancer cells in a p53-independent manner.

Calcitriol inhibits migration and invasion of renal cell carcinoma cells by suppressing Smad2/3-, STAT3- and ß-catenin-mediated epithelial-mesenchymal transition.

Low vitamin D status is associated with progression in patients with renal cell carcinoma (RCC). The present study found that vimentin, a mesenchymal marker, was accordingly upregulated, and E-cadherin, an epithelial marker, was downregulated in RCC patients with low vitamin D status. Thus, we investigated the effects of calcitriol or vitamin D3, an active form of vitamin D, on epithelial-mesenchymal transition (EMT) in RCC cells. RCC cells were treated by two models. In model 1, three RCC cell lines, ACHN, 786-O and CAKI-2, were incubated with either LPS (2.0 µg/mL) or transforming growth factor (TGF)-ß1 (10 ng/mL) in the presence or absence of calcitriol (200 nmol/L). In model 2, two RCC cell lines, ACHN and CAKI-2, were incubated with calcitriol (200 nmol/L) only. Calcitriol inhibited migration and invasion not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated RCC cells. Moreover, calcitriol suppressed E-cadherin downregulation and vimentin upregulation not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated ACHN and CAKI-2 cells. Calcitriol attenuated LPS-induced upregulation of MMP-2, MMP-7, MMP-9, MMP-26 and urokinase-type plasminogen activator (u-PA) in ACHN cells. In addition, calcitriol blocked TGF-ß1-induced nuclear translocation of ZEB1, Snail and Twist1 in ACHN and CAKI-2 cells. Mechanistically, calcitriol suppressed EMT through different signaling pathways: (i) calcitriol suppressed Smad2/3 phosphorylation by reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-ß1-stimulated RCC cells; (ii) calcitriol inhibited signal transducer and activator of transcription (STAT)3 activation in LPS-stimulated RCC cells; (iii) calcitriol inhibited ß-catenin/TCF-4 activation by promoting integration of VDR with ß-catenin in TGF-ß1-unstimulated RCC cells. Taken together, calcitriol inhibits migration and invasion of RCC cells partially by suppressing Smad2/3-, STAT3- and ß-catenin-mediated EMT.

Serum nesfatin-1 is associated with testosterone and the severity of erectile dysfunction.

This cross-sectional study aimed to evaluate serum nesfatin-1 concentrations in patients with erectile dysfunction (ED). Patients with ED were selected from the Department of Urology of the Second Affiliated Hospital of Anhui Medical University. The International Index of Erectile Function-5 (IIEF-5) was used to evaluate the severity of ED. Serum nesfatin-1 and gonadal hormone levels, including luteinising hormone (LH), follicle-stimulating hormone (FSH) and testosterone were measured. The IIEF-5 scores (t = -21.034, p < .001) and nesfatin-1 levels (t = -7.043, p < .001) in patients with ED were significantly lower than in healthy controls. Moreover, patients with ED showed decreased testosterone levels (t = -3.478, p = .001), whereas there were no significant differences in serum levels of FSH (t = -0.088, p = .930) and LH (t = 1.114, p = .270) between the two groups. Furthermore, positive relationships were found between serum nesfatin-1 and testosterone concentrations (r = .742, p = .001) and IIEF-5 scores (r = .395, p = .009) in ED patients. Additionally, based on receiver operating characteristic curve analysis, the area under curve for nesfatin-1 was 0.884 with 83.3% sensitivity and 81.4% specificity in discriminating ED patients from healthy controls. The decrease in serum nesfatin-1 level may be related to testosterone and the severity of ED.

Relative Computed Tomography (CT) Enhancement Value for the Assessment of Microvascular Architecture in Renal Cell Carcinoma.

BACKGROUND To investigate the correlation between the relative computed tomography (CT) enhancement value and the microvascular architecture in different pathologic subtypes of renal cell carcinoma (RCC). MATERIAL AND METHODS This retrospective study included 55 patients with pathologically confirmed RCC. Immunohistochemistry for CD34 was performed for all surgical specimens. Microvascular architecture parameters (density, area, diameter, and perimeter) for the microvessels and the microvessels with lumen were determined. The CT scan was performed during arterial phase or venous phase. The correlation of parameters on CT and tumor angiogenesis was investigated. RESULTS Density of microvessels showed a positive correlation with CT values of tumors, ratios of tumor to cortex, and differences of tumor and medulla, but no correlation with CT value ratio of tumor to aorta or tumor to medulla. CT parameters were positively correlated with microvascular parameters. However, no CT parameter differences between hypo-vascular clear cell RCC and papillary RCC was observed. Strikingly, the density and area of the microvessels were significantly higher in hypo-vascular clear cell RCC than that in papillary RCC, while the density of the microvessels with lumen in the cyst-present RCC was significantly higher than that in the cyst-absent RCC. The values (especially those of microvessels with lumen) of area density, diameter, and perimeter were higher in the capsule-absent RCC than in the capsule-present RCC. CONCLUSIONS The relative CT enhancement value of RCC was associated with vascular architecture parameters including density, area, and perimeter. Quantitative and semi-quantitative parameters on enhanced CT may shed some light on tumor vasculature and function as indicators of the biological behavior of RCC.

Benzidine induces epithelial-mesenchymal transition in human uroepithelial cells through ERK1/2 pathway.

Prolonged benzidine exposure is a known cause of urothelial carcinoma (UC). Benzidine-induced epithelial-to-mesenchymal transition (EMT) is critically involved in cell malignant transformation. The role of ERK1/2 in regulating benzidine-triggered EMT has not been investigated. This study was to investigate the regulatory role of ERK1/2 in benzidine-induced EMT. By using wound healing and transwell chamber migration assays, we found that benzidine could increase SV-HUC-1 cells invasion activity, western blotting and Immunofluorescence showed that the expression levels of Snail, ß-catenin, Vimentin, and MMP-2 were significantly increased, while, the expression levels of E-cadherin, ZO-1 were decreased. To further demonstrate the mechanism in this process, we found that the phosphorylation of ERK1/2, p38, JNK and AP-1 proteins were significantly enhanced compared to the control group (*P < 0.05). Afterward, treated with MAPK pathways inhibitors, only ERK inhibitor（U0126）could reduce the expression of EMT markers in SV-HUC-1 cells, but not p38 and JNK inhibitor（SB203580, SP600125）, which indicated that benzidine induces the epithelial-mesenchymal transition in human uroepithelial cells through ERK1/2 pathway. Taken together, findings from this study could provide into the molecular mechanisms by which benzidine exerts its bladder-cancer-promoting effect as well as its target intervention.

Morphological changes of the thoracic duct and accessory lymphatic channels in patients with chylothorax: detection with unenhanced magnetic resonance imaging.

OBJECTIVES: To characterise the imaging findings of patients with chylothorax and to identify the leak site using unenhanced MRI. METHODS: Seven patients with chylothorax and 30 healthy individuals (as the control group) underwent three-dimensional heavily and routine T2-weighted MRI. Morphological changes and diameters of the thoracic duct, chyloma display, and some dilated accessory lymph channels were evaluated and measured. The differences between patients and the control group were compared. The leak sites of the thoracic duct and parietal pleura were also identified. RESULTS: The patients had a higher display rate of the entire thoracic duct and some accessory lymphatic channels, enlarged diameters and tortuous configuration of the thoracic duct, and existence of chylomas compared with the control group (P < 0.05). Seven leaks of the thoracic duct in five patients and five leaks of the parietal pleura in four patients were identified. Close relationships between the leak of thoracic duct and the chylomas or the meshworks of tiny lymphatics were found (P < 0.05). CONCLUSION: Unenhanced MRI appears reliable in the detection of morphological changes of thoracic lymphatics and in the identification of chyloma and leak sites in patients with chylothorax, which helps appropriate treatment planning and follow-up.

Development and External Validation of a Nomogram Including Body Composition Parameters for Predicting Early Recurrence of Hepatocellular Carcinoma After Hepatectomy.

RATIONALE AND OBJECTIVES: Body composition, including adipose and muscle tissues, evaluated by computer tomography is correlated with the prognosis of hepatocellular carcinoma (HCC). However, its relationship with early recurrence (ER) remains unclear. This study aimed at establishing and validating a nomogram based on body composition and clinicopathological indices to predict ER of HCC. MATERIALS AND METHODS: One hundred ninety-five patients from institution A formed the training cohort and internal validation cohort, and 50 patients from institution B formed the external validation cohort. Independent predictors of ER were identified using LASSO and Cox regression analyses. The performance of nomogram was evaluated using the calibration curve, concordance index (C-index), area under the curve (AUC), and decision curve analysis (DCA). RESULTS: After data screening, the nomogram was constructed using eight independent predictors of ER, including the tumor size, alpha fetoprotein, body mass index, Edmondson Steiner grade, visceral adipose tissue radiodensity, intermuscular adipose tissue index, intramuscular adipose tissue content, and skeletal muscle area. The calibration curve exhibited excellent concordances, with C-indices of 0.808 (95%CI: 0.771-0.860), 0.802 (95%CI: 0.747-0.942), and 0.804 (95%CI: 0.701-0.861) in training, internal validation, and external validation cohorts, respectively. In addition, compared to conventional staging systems and pure clinical model, the nomogram exhibited a higher AUC and wider range of threshold probabilities in DCA, which indicated better discriminative ability and greater clinical benefit. Finally, patients with nomogram scores of <183.07, 183.07-243.09, and >243.09 were considered to have low, moderate, and high risks of ER, respectively. CONCLUSION: The nomogram exhibits excellent ER predictive ability for patients with HCC who underwent hepatectomy.

nc-RNA-mediated high expression of CDK6 correlates with poor prognosis and immune infiltration in pancreatic cancer.

BACKGROUND: Emerging evidence manifests that cyclin-dependent kinase 6 (CDK6) plays an essential part in the initiation and progression of several types of human cancer, and its descending expression is correlated with an adverse prognosis. However, the precise role of CDK6 in Pancreatic cancer (PC) remains obscure. AIMS: To identify the potential ceRNA regulatory axis of CDK6 in PC and explore its relationship with immune cells and immune checkpoints. MATERIALS & METHODS: Using The Cancer Genome Atlas TCGA and GTEx data analyze the expression and survival of CDK6 in patients in pan-cancer, and cellular experiments were performed to verify the effect of CDK6 on cell function. Using GEPIA and STARBASE databases to analyze prognosis, expression and survival, and identify non coding RNA (ncRNA) that mediates CDK6 overexpression. The TIMER 2.0 database was used for immune correlation analysis. RESULTS: We revealed CDK6 might be an oncogene in PC, and the HOXA11-AS /NR2F1-AS1- miR-454-3p axis was identified as the possible upstream ncRNA-associated pathway of CDK6 in PC. In addition, CDK6 show significant association with three immune checkpoints (PD-L1, PD-L2, and HAVCR2), the infiltration level of immune cells, and immunity biomarkers. DISCUSSION: We discussed some applications of CDK6 in breast cancer, melanoma, and hemorrhagic malignancies. The role of miR-15a-5p, HOXA11-AS and NR2F1-AS1 in tumor development was also discussed based on existing studies. The potential mechanism of CDK6 affecting immune cells in pancreatic cancer was discussed. CONCLUSIONS: Overall, these results established that nc-RNA-mediated high expression of CDK6 is associated with patient outcomes and immune invasion in pancreatic cancer.

Vitamin D deficiency aggravates growth and metastasis of prostate cancer through promoting EMT in two ß-catenin-related mechanisms.

Increasing evidence has demonstrated that vitamin D deficiency is associated with prostate cancer progression, but its mechanism remains unclear. This study investigated effects of vitamin D deficiency on growth and metastasis of prostate cancer. Nude mice and Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed with vitamin D-deficient (VDD) diets. Prostate cancer growth was aggravated in VDD diet-fed nude mice and TRAMP mice. Invasion and metastasis of prostate cancer were exacerbated in VDD diet-fed TRAMP mice. In vitro experiments showed that calcitriol, an active vitamin D3, inhibited migration and invasion in transforming growth factor (TGF)-ß1 -stimulated and -unstimulated PC-3 and DU145 cells. Mechanistically, calcitriol inhibited epithelial-mesenchymal transition (EMT) in TGF-ß1 -stimulated and -unstimulated DU145 cells. Unexpectedly, calcitriol did not inhibit Smad2/3 phosphorylation in TGF-ß1-stimulated DU145 cells. Instead, calcitriol downregulated expression of proliferation-, metastasis- and EMT-related genes, includes Cyclin D1, MMP7, and Zeb1, by inhibiting interaction between TCF4 and ß-catenin. In addition, calcitriol promoted interaction between cytoplasmic VDR and ß-catenin, reduced ß-catenin phosphorylation and elevated ß-catenin/E-cadherin adherens junction complex formation. We provide novel evidence that vitamin D deficiency aggravates growth and metastasis of prostate cancer possibly through promoting EMT in two ß-catenin-related mechanisms.

Melatonin alleviates intrarenal CaOx crystals deposition through inhibiting LPS-induced non-canonical inflammasome-mediated renal tubular epithelial cells pyroptosis.

Urinary tract infection has long been considered a complication rather than etiology of calcium oxalate (CaOx) nephrolithiasis. This study aimed to explore the role of lipopolysaccharide (LPS), an important component of Gram-negative bacteria, on CaOx nephrolithiasis formation and antagonistic effect of melatonin. Male C57BL/6 mice were intraperitoneally injected with glyoxylate acid (80 mg/kg) daily for 7 days to construct CaOx nephrolithiasis model. A single dose of LPS (2.0 mg/kg) was given 2 h before the second glyoxylate acid treatment in the presence or absence of melatonin (25 mg/kg). Our results found that LPS promoted adhesion of CaOx crystals to renal tubular epithelial cells (RTECs) and intrarenal CaOx crystals deposition. Protein levels of cleaved Caspase-11, N-terminal of cleaved GSDMD (GSDMD-N), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved Caspase-1, several markers of non-classical inflammasome activation were upregulated in LPS-treated mouse kidneys and HK-2 cells. Moreover, the number of GSDMD pores was increased in LPS-treated HK-2 cell membrane. Melatonin inhibited Caspase-11 cleavage and antagonized the subsequent LPS-mediated upregulation of GSDMD-N, NLRP3 and cleaved Caspase-1 in kidney tissues and HK-2 cells. In addition, melatonin reduced membrane localization of GSDMD-N and the number of GSDMD pores in LPS-treated HK-2 cells. Accordingly, melatonin inhibited LPS-induced IL-1ß and IL-18 in mouse serum and HK-2 culture supernatant. Importantly, melatonin alleviated LPS-induced crystal-cell interactions and intrarenal CaOx crystals deposition. We provide experimental evidence that LPS promoted CaOx nephrolithiasis formation by inducing non-canonical inflammasome-mediated RTECs pyroptosis. Melatonin alleviated CaOx nephrolithiasis formation through inhibiting LPS-induced non-canonical inflammasome-mediated RTECs pyroptosis.

[Value of 3T magnetic resonance dynamic contrast-enhanced and diffusion-weighted imaging in differential diagnosis of musculoskeletal tumors].

OBJECTIVE: To evaluate the value of magnetic resonance dynamic contrast-enhanced (MR-DCE) and magnetic resonance diffusion-weighted imaging (MR-DWI) in the differentiation of benign and malignant musculoskeletal tumors. METHODS: Sixty-three patients with pathologically confirmed musculoskeletal tumors were examined with MR-DCE and MR-DWI. Using single shot spin echo planar imaging sequence and different b values of 400, 600, 800 and 1000 s/mm(2), we obtained the apparent diffusion coefficient (ADC) of the lesions. ADC values were measured before and after MR-DCE, with a b value of 600 s/mm(2). The 3D fast acquired multiple phase enhanced fast spoiled gradient recalled echo sequence was obtained for multi-slice of the entire lesion. The time-signal intensity curve (TIC), dynamic contrast-enhanced parameters, maximum slope of increase (MSI), positive enhancement integral, signal enhancement ratio, and time to peak (T(peak)) were also recorded. RESULTS: ADC showed no significant difference between benign and malignant tumors when the b value was 400, 600, 800, or 1000 s/mm(2), and it was not significantly different between benign and malignant tumors in both pre-MR-DCE and post-MR-DCE with b value of 600 s/mm(2). TIC were classified into four types type1 showed rapid progression and gradual drainage; type2 showed rapid progression but had no or slight progression; type 3 showed gradual progression; and type 4 had no or slight progression. Most lesions of type1 or type2 were malignant, whereas most lesions of type 3 or type 4 were benign. When using type1 and type 2 as the standards of malignancy, the diagnostic sensitivity and specificity was 87.23% and 50.00%, respectively. The types of TIC showed significant difference between benign and malignant musculoskeletal tumors(χ(2)=17.009,P=0.001). When using MSI 366.62 ± 174.84 as the standard of malignancy, the diagnostic sensitivity and specificity was 86.78% and 78.67%, respectively. When using T(peak)≤70s as the standard of malignancy, the diagnostic sensitivity and specificity was 82.89%and 85.78%, respectively. Positive enhancement integral and signal enhancement ratio showed no significant difference between benign and malignant musculoskeletal tumors. CONCLUSIONS: TIC, MSI and T(peak) of MR-DCE are valuable in differentiating benign from malignant musculoskeletal tumors. T(peak) has the highest diagnostic specificity, and TIC has the highest diagnostic sensitivity. The mean ADC value are no significant difference between benign and malignant tumors.

Mitochondria-derived reactive oxygen species are involved in renal cell ferroptosis during lipopolysaccharide-induced acute kidney injury.

Our earlier studies indicated that reactive oxygen species (ROS) were involved in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). The present study aimed to explore the role of mitochondria-derived ROS on renal cell ferroptosis during LPS-induced AKI. Male CD-1 mice were intraperitoneally injected with LPS (2.0 mg/kg). Renal MDA and 4HNE residue, two markers of lipid peroxidation, were increased in LPS-exposed mice. Oxidized lipids were detected in LPS-treated human HK-2 cells. In vivo, ferroptosis-characteristic ultrastructure changes, including cell volume reduction, nuclear pyknosis and smaller mitochondria, were shown in renal cortex. In vitro, abnormal alteration of mitochondrial membrane potential was observed in LPS-treated human HK-2 cells. Ferrostatin-1, a specific inhibitor of ferroptosis, attenuated LPS-evoked renal lipid peroxidation, ferroptosis-characteristic mitochondrial damage and renal cell death. Mechanistically, mitochondria-derived ROS were elevated in LPS-stimulated HK-2 cells. MitoQ, a mitochondria-targeted antioxidant, almost completely scavenged LPS-stimulated mitochondrial ROS in human HK-2 cells. Moreover, pretreatment with MitoQ attenuated LPS-induced GSH depletion and lipid peroxidation in mouse kidney. Finally, pretreatment with MitoQ alleviated LPS-induced renal cell death and AKI. Taken together, these results suggest that mitochondria-derived ROS contribute, at least partially, to renal cell ferroptosis during LPS-induced AKI. Mitochondria-targeted antioxidants may be potential therapeutic agents for sepsis-induced AKI.

Transcutaneous electrical nerve stimulation on ST36 and SP6 acupoints prevents hyperglycaemic response during anaesthesia: a randomised controlled trial.

BACKGROUND AND OBJECTIVE: Hyperglycaemia is a common result of stress signals caused by pain and surgical procedure. Volatile anaesthetics also directly manipulate glucose homeostasis by affecting pancreatic insulin release and induce hyperglycaemia without surgical stress. We determined the preoperative application of transcutaneous electrical nerve stimulation (TENS) to the Chinese acupoints ST36 (Zusanli) and SP6 (Sanyinjiao) as a complementary therapy for controlling plasma glucose and improving insulin resistance during anaesthesia. METHODS: We designed a single-blind, randomised controlled clinical study of female patients, scheduled for elective hysterectomy. The 52 patients consented to enrolment and were assigned to receive either TENS (n = 26) on bilateral ST36 and SP6 acupoints with continuous mode at a frequency of 15 Hz and the intensity of 10 mA synchronously for 30 min or non-stimulation (placebo group, n = 26) preoperatively. Haemodynamics, blood glucose and plasma insulin were measured during general anaesthesia. RESULTS: At baseline, there was no significant difference between the TENS group and the placebo group in plasma glucose and insulin levels as well as homeostasis model assessment (HOMA) index. In the placebo group, plasma glucose, insulin and HOMA index increased during induction of general anaesthesia, surgical incision, and throughout the operation. Plasma glucose and insulin levels as well as HOMA index were significantly lower in the TENS group as compared to the placebo group at different time points after discontinuation of TENS application. These results indicate the positive effect of prevention of hyperglycaemia and the increased sensitivity of plasma insulin in the TENS group. CONCLUSION: We found TENS at bilateral ST36 and SP6 acupoints to be an alternative means of managing the plasma glucose level and improving insulin resistance perioperatively.

[Correlation analysis between meiotic recombination frequencies and age in human spermatocyte].

Faithful meiotic recombination is essential for the segregation of homologous chromosomes and the formation of normal haploid gametes. Little is known about the mechanism of meiotic recombination in human germ cells. MLHl (a DNA mismatch repair protein) foci on synaptonemal complexes (SCs) at prophase I of meiosis can be used to examine recombination frequency. In 10 fertile men, the mean number of MLH1 foci per cell in all donors was 49.4 with a range from 33 to 63. There was significant variation in the recombination frequency found among 10 normal individuals: the mean frequencies of chromosomal recombination foci ranged from 47 to 52.7. The bivalents without recombination focus were rare, with a frequency of only 0.4%. Thus, achiasmate chromosomes appeared to be rare in human male meiosis. Spearman correlation analysis between age and the frequencies of recombination foci failed to get any significantly statistical correlation, suggesting that aging contributes nothing to the variation among individuals.

[Application value of 3T 1H-magnetic resonance spectroscopy in diagnosing tumors of bone and soft tissue].

OBJECTIVE: To study benign and malignant bone and soft tissue tumors with 1H-magnetic resonance spectroscopy (1H-MRS) at 3 Tesla MR scanner and assess the value of 1H-MRS in diagnosing bone and soft tissue tumors and distinguishing benign from malignant tumors. METHODS; Totally 49 patients with clinically and pathologically confirmed bone and soft tissue tumors were enrolled in this study. 1H-MRS was performed before treatment with point-resolved spectroscopy sequence. The imaging characteristics of 1H-MRS for bone and soft tissue tumors were observed and the possible differences between benign and malignant tumors was compared. Since spectra were directly found under single-voxel proton MRS brain examination, the peak height of choline containing compounds (Cho) opposite to the creatine (Cr) and the Cho peak were observed, and then the malignancies of the tumors were judged. Cho/Cr value was calculated and used to distinguishing benign tumors from malignancies. RESULTS: 1H-MRS spectra of bone and soft tissue tumors were different from those of the normal muscles, and such difference also existed between benign and malignant tumors. The Cho peak disappeared or was extremely low among benign tumors. The Cho/Cr values of malignant tumors and benign tumors were 3.13 +/- 0.9 and 1.34 +/- 1.02, respectively (P = 0.02). Using 1.79 as the threshold value, the Cho/Cr value had sensitivity, specificity, and accuracy of 94%, 80%, and 90%, respectively, in diagnosing malignancies. CONCLUSIONS: The increased Cho level, as measured by 1H-MRS, is related with the bone and soft tissue malignant tumor. Cho/Cr value is useful in distinguishing benign tumors from malignancies. 1H-MRS can be an important supplement to the conventional magnetic resonance imaging.

Sirt1 inhibits kidney stones formation by attenuating calcium oxalate-induced cell injury.

Cell injury is a necessary and critical event during CaOx kidney stone formation. Sirt1 exerts a number of pleiotropic effects, protecting against renal cell injury. This study aims to explore the relationship between Sirt1 and CaOx kidney stone formation and the underlying mechanism. Sirt1 expression in renal tissues or HK-2 cells was detected by Western blot, immunohistochemistry and immunofluorescence. Apoptosis in renal tissues was examined by TUNEL staining. Renal pathological changes and the crystals deposition were detected by hematoxylin-eosin and Von Kossa staining. Crystal-cell adhesion and cell injury in HK-2 cells were assessed by atomic absorption spectrometry and flow cytometry, respectively. Sirt1 expression in nephrolithiasis patients was downregulated and the level of apoptosis was increased. Further study found that Sirt1 expression was decreased in both in vivo and in vitro models. Interestingly, the levels of cell injury were elevated in vivo and in vitro models. Suppressing Sirt1 expression promoted COM-induced crystal-cell adhesion and exacerbated cell injury. In contrast, increasing the expression of Sirt1 by lentivirus transfection in vitro and resveratrol administration in vivo, alleviated crystal deposition and cell damage. Our findings suggest that Sirt1 could inhibit kidney stone formation, at least in part, through attenuating CaOx -induced cell injury.

Melatonin Inhibits Migration and Invasion in LPS-Stimulated and -Unstimulated Prostate Cancer Cells Through Blocking Multiple EMT-Relative Pathways.

PURPOSE: Gram-negative bacteria are usually found in prostate cancer (PCa) tissues. This study aims to investigate the role of lipopolysaccharide (LPS), a glycolipid compound found in the outer membrane of gram-negative bacteria, on the migration and invasion of PCa cells, and to evaluate the protective effect of melatonin. MATERIALS AND METHODS: DU145, PC-3 and LNCaP cells were incubated with LPS in the presence or absence of melatonin. Wound healing and Transwell assays were used to analyze migration and invasion of PCa cells. RT-PCR and Western blotting were used to assess the mRNA and protein levels, respectively. Co-IP was used to analyze ß-catenin ubiquitination. RESULTS: Our results showed that LPS promoted migration and invasion of PCa cells. In addition, LPS stimulated inflammatory reaction and induced epithelial-mesenchymal transition (EMT) in PCa cells by activating several TLR4 downstream pathways. Specifically, LPS promoted NF-κB/IL-6/STAT3 signal transduction. In addition, LPS upregulated phosphorylation levels of cytoplasmic AKTSer473 and GSK-3ßSer9. Moreover, LPS induced phosphorylation of GSK-3ßSer9 in the "disruption complex", and then inhibited phosphorylation and ubiquitination of cytoplasmic ß-catenin, leading to ß-catenin nuclear translocation. Interestingly, melatonin inhibited invasion and migration not only in LPS-stimulated but also in LPS-unstimulated PCa cells. Melatonin suppressed PCa cells migration and invasion by blocking EMT mediated by IL-6/STAT3, AKT/GSK-3ß and ß-catenin pathways. CONCLUSION: This study provides evidence that melatonin inhibits migration and invasion through blocking multiple TLR4 downstream EMT-associated pathways both in LPS-stimulated and -unstimulated PCa cells. Our results provide new insights into the role of bacterial infection in PCa metastasis and a potential therapeutic agent.

Influence of arm position change from adduction to abduction on intracavitary electrocardiogram.

PURPOSE: The aim of this study is to evaluate the influence of arm movements from adduction to abduction on intracavitary electrocardiogram and the position of a catheter tip. METHODS: Overall, 192 peripherally inserted central catheter lines were placed under intracavitary electrocardiogram guidance and 188 of them were enrolled in the study. The catheter was first placed at a time point corresponding to the peak P wave with the arm in adduction. The arm was then abducted to 90° without changing catheter insertion length. During the procedure, basal electrocardiogram, intracavitary electrocardiogram, and radiographs with the arm in adduction and abduction were recorded. Amplitude wave changes and catheter movements were measured on electrocardiogram records and radiographs, respectively. RESULTS: In 188 cases, the P wave displayed typical changes, and 97.8% (184/188) catheters were successfully placed correctly. At the peak P wave, the amplitude of the peak P wave was 8.64 times greater than that of the basal P wave, and the P/R ratio was 0.61. When the arm was abducted to 90°, the amplitude of the P wave dropped to 57% of its peak, P/R decreased from 0.61 to 0.34, and the catheter tip moved cephalad 1.00 and 0.77 vertebral body units in male and female patients, respectively. CONCLUSION: Peripherally inserted central catheter moves toward the heart when the arm position changes from abduction to adduction. Peripherally inserted central catheter tip placement at the peak P wave with patient's arm in adduction is accurate and can prevent the catheter from advancing too low. R wave can function as a reference for observing P wave changes during peripherally inserted central catheter placement.

Morphological features and clinical feasibility of thoracic duct: detection with nonenhanced magnetic resonance imaging at 3.0 T.

PURPOSE: To evaluate the detection of the thoracic duct using nonenhanced magnetic resonance imaging (MRI) and to determine the influence of some related disorders on the lymphatic duct. MATERIALS AND METHODS: Highly fluid-sensitive sequence and fat-suppressed T2-weighted imaging (FS-T2WI) were performed in a total of 139 cases. The axial and coronal images were used to locate the thoracic duct and the measurement and evaluation of its dimensions were performed using a 3D maximum intensity projection (MIP) reconstruction image. The differences in the dimensions among control, portal hypertension, and common bile duct obstruction groups were compared using one-way analysis of variance. RESULTS: The cisterna chyli was shown in 91% of cases on FS-T2WI, while the thoracic duct appeared in 70% of the MIP images. The common configuration of the cisterna chyli was tubular or saccular in 73%. Eighty thoracic ducts had a slight turn declining to the left at the level of T8-10. There was a significant difference in the transverse diameter of the thoracic duct between the portal hypertension group and other groups (F = 5.638, P = 0.005). CONCLUSION: Nonenhanced MRI is feasible for locating and depicting the morphological features of the thoracic duct. Portal hypertension may influence the dimension of the thoracic duct.

[Evaluation of blood oxygen level in hepatocellular carcinoma with noninvasive magnetic resonance multi-echo R2* technique and its clinical significance].

OBJECTIVE: To probe the relationship of clinical and pathological features of hepatocellular carcinoma (HCC) with the blood oxygen level by the technique of noninvasive magnetic resonance multi-echo R2*. METHODS: Multi-echo R2* sequence was carried out pre-operatively in a total of 46 patients with pathologically proved HCC. The T2* and R2* values of HCC, liver, spleen and paraspinous muscle on T2* and R2* maps and the ratios of HCC to liver (H/L), spleen (H/S) and muscle (H/M) were calculated. Different groups were defined according to such clinical parameters as the serum AFP level, lesion dimension, Edmondson's grade, ascites, capsula, liver cirrhosis, intrahepatic daughter foci or tumor-emboli in portal vein respectively. The differences in T2* and R2* values and the ratios between different groups were analyzed. RESULTS: In contrast with T2* value, the R2* value of HCC was less than that of liver or spleen (P < 0.05). Difference in R2* ratio of H/M (0.81 +/- 0.26 vs. 1.23 +/- 0.39) was found between positive and negative groups of AFP (P = 0.047, t = 2.248). And so was the same difference (0.83 +/- 0.24 vs. 1.23 +/- 0.43) between the lesions with or without capsula (P = 0.046, t = 2.257). The R2* ratio of H/S in hepatic cirrhosis group (1.01 +/- 0.58) was higher than that in noncirrhosis one (0.53 +/- 0.17) (P = 0.035, t = 2.247) whereas the T2* ratio of H/S was reversed (1.42 +/- 0.92 vs. 2.64 +/- 1.15) (P = 0.036, t = 2.230). The differences in T2* ratio of H/M in the group with or without intrahepatic daughter foci (1.18 +/- 0.47 vs. 2.24 +/- 1.71) (P = 0.048, t = 2.115), and in T2* value in the group with or without tumor-emboli in portal vein (27.24 +/- 11.90 ms vs. 46.70 +/- 38.40 ms) (P = 0.049, t = 2.046) were shown to be significant. However, no differences in MR parameters between other groups were observed (P > 0.05). CONCLUSION: The blood oxygen level parameters, R2* and T2* values and the ratios are related to some clinical and pathological features of HCC. And the blood oxygen level is affected by multiple factors.