Pars plana vitrectomy for retinal detachment using perfluoro-n-octane as intraoperative tamponade: a multicenter, randomized, non-inferiority trial.

AIM: To evaluate the efficacy and safety of perfluoro-n-octane (PFO) for ophthalmic surgery versus F-Octane as an intraoperative tamponade in pars plana vitrectomy (PPV) in management of retinal detachment. METHODS: This multicenter, prospective, randomized, double-masked, parallel-controlled, non-inferiority trial was conducted in three ophthalmology clinical centers in China. Patients with retinal detachment, who were eligible for PPV were consecutively enrolled. Participants were assigned to PFO for ophthalmic surgery or F-Octane for intraocular tamponade in a 1:1 ratio. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) measurement, and dilated fundus examination were performed preoperatively and at 1, 7±1, 28±3d postoperatively. The primary outcome was complete retinal reattachment rate at postoperative day one. The non-inferiority margin was set at 9.8%. The secondary outcomes included intraoperative retinal reattachment rate, and mean changes in IOP and BCVA from baseline to 1, 7±1, 28±3d postoperatively, respectively. Safety analyses were presented for all randomly assigned participates in this study. RESULTS: Totally 124 eligible patients completed the study between Mar. 14, 2016 and Jun. 7, 2017. Sixty of them were randomly assigned to the PFO for ophthalmic surgery group, and 64 were assigned to the F-Octane group. Baseline characteristics were comparable between the two groups. Both groups achieved 100% retinal reattachment at postoperative day one (difference 0, 95%CI: -6.21% to 5.75%, P=1). The pre-defined noninferiority criterion was met. No significant difference was observed in intraoperative retinal reattachment rate (difference 1.77%, P=0.61), mean changes in IOP (difference 0.36, -0.09, 2.22 mm Hg at 1, 7±1, 28±3d postoperatively, with all P>0.05) and BCVA (difference 0.04, -0.02, 0.06 logMAR at 1, 7±1, 28±3d postoperatively, all P>0.05) between the two groups. No apparent adverse events related to the utilization of PFO were reported. CONCLUSION: In patients with retinal detachment undergoing PPV, PFO for ophthalmic surgery is non-inferior to F-Octane as an intraocular tamponade, and both are safe and well-tolerated.

miR-146a-5p Alleviates Radiation-Induced Liver Fibrosis by Regulating PTPRA-SRC Signaling in Mice.

Patients with hepatobiliary tumors who accept radiotherapy are at risk for radiation-induced liver fibrosis. MicroRNAs (miRNAs) have been implicated in the pathogenesis of radiation-induced liver damage and possess potential as novel biomarkers and therapeutic targets. However, the role of miR-146a-5p in radiation-induced liver fibrosis is less well understood. The current study was designed to evaluate the role of miR-146a-5p in radiation-induced liver fibrosis in mice and to investigate the possible mechanisms involved in miR-146a-5p-mediated effects. The experiments were performed on Institute of Cancer Research (ICR) mice which received fractionated radiation (30 Gy in 5 fractions) to the liver. The results show radiation could induce histopathological changes, liver dysfunction and fibrosis accompanied with decreased miR-146a-5p expression. miR-146a-5p agomir treatment resulted in recovery of liver function and reduced the amount of alpha-smooth muscle actin (α-SMA), collagen 1, protein tyrosine phosphatase receptor type A (PTPRA) and phosphorylated SRC in the livers of irradiated mice. Therefore, our study reveals that miR-146a-5p inhibits the progression of hepatic fibrosis after radiation treatment. And the beneficial role of miR-146a-5p may be relevant to PTPRA-SRC signaling pathway.

[Spatiotemporal charactersitics of decoupling between land surface thermal environment and ecosystem ser-vice value in Pearl River Delta Urban Agglomeration, China]. / ç ä¸‰è§’åŸŽå¸‚ç¾¤åœ°è¡¨çƒ­çŽ¯å¢ƒä¸Žç”Ÿæ€ç³»ç»ŸæœåŠ¡ä»·å€¼è§£è€¦çš„æ—¶ç©ºç‰¹å¾.

The Pearl River Delta Urban Agglomeration (PRDUA) is a highly urbanized region in China. The urbanized climate, especially the heat island effect, has a significant impact on urban ecosystems and habitats. Based on MODIS land surface temperature (LST) data and land cover data in 2000, 2005, 2010, 2015, and 2019, we quantified the land surface thermal environment and ecosystem service value (ESV), analyzed the decoupling between LST and ESV in the PRDUA from 2000 to 2019 using the decoupling analysis model, revealed the trade-off between them, and analyzed the spatiotemporal variation of the synergistic state between LST and ESV in PRDUA. The results showed that, from 2000 to 2019, the spatial pattern of land surface thermal environment in the PRDUA was relatively stable in time series but showed spatial variation with high fluctuation in the core area and low fluctuation in the peripheral area. The ESV of the PRDUA showed a trend of stable spatial distribution and decreasing in time series. The ESV of all the nine cities in PRDUA decreased by more than 9%. The decoupling between land surface thermal environment and the overall ESV of the PRDUA, as well as with the values of provisioning, regulating and support services, was dominated by weak negative decoupling and strong negative decoupling, showing a more significant trade-off, which indicated that the ecosystems of the PRDUA were still significantly influenced by the environmental characteristics of urbanization, and that the spatiotemporal variation of the decoupling states was related to the spatial variation of urbanization levels in PRDUA. The formulation of future ecological policies in the PRDUA must consider the differences in urbanization levels and the differences in the trade-offs between urbanized environments and ecosystems to precisely formulate ecological control and restoration plans and improve the efficiency and implementation effects of ecological planning.

CircTUBD1 Regulates Radiation-induced Liver Fibrosis Response via a circTUBD1/micro-203a-3p/Smad3 Positive Feedback Loop.

Background and Aims: Radiation-induced liver fibrosis (RILF), delayed damage to the liver (post-irradiation) remains a major challenge for the radiotherapy of liver malignancies. This study investigated the potential function and mechanism of circTUBD1 in the development of RILF. Methods: By using a dual luciferase assay, RNA pull-down assays, RNA sequencing, chromatin immunoprecipitation (known as ChIP) assays, and a series of gain- or loss-of-function experiments, it was found that circTUBD1 regulated the activation and fibrosis response of LX-2 cells induced by irradiation via a circTUBD1/micro-203a-3p/Smad3 positive feedback loop in a 3D system. Results: Knockdown of circTUBD1 not only reduced the expression of α-SMA, as a marker of LX-2 cell activation, but also significantly decreased the levels of hepatic fibrosis molecules, collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and connective tissue growth factor (CTGF) in a three-dimensional (3D) culture system and RILF model in vivo. Notably, knockdown of circTUBD1 alleviated early liver fibrosis induced by irradiation in mice models. Conclusions: This study is the first to reveal the mechanism and role of circTUBD1 in RILF via a circTUBD1/micro-203a-3p/Smad3 feedback loop, which provides a novel therapeutic strategy for relieving the progression of RILF.

Protein profiling of hemolymph in Haemaphysalis flava ticks.

BACKGROUND: Tick hemolymph bathes internal organs, acts as an exchange medium for nutrients and cellular metabolites, and offers protection against pathogens. Hemolymph is abundant in proteins. However, there has been limited integrated protein analysis in tick hemolymph thus far. Moreover, there are difficulties in differentiating tick-derived proteins from the host source. The aim of this study was to profile the tick/host protein components in the hemolymph of Haemaphysalis flava. METHODS: Hemolymph from adult engorged H. flava females was collected by leg amputation from the Erinaceus europaeus host. Hemolymph proteins were extracted by a filter-aided sample preparation protocol, digested by trypsin, and assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). MS raw data were searched against the UniProt Erinaceidae database and H. flava protein database for host- and tick-derived protein identification. Protein abundance was further quantified by intensity-based absolute quantification (iBAQ). RESULTS: Proteins extracted from hemolymph unevenly varied in size with intense bands between 100 and 130 kDa. In total, 312 proteins were identified in the present study. Therein 40 proteins were identified to be host-derived proteins, of which 18 were high-confidence proteins. Top 10 abundant host-derived proteins included hemoglobin subunit-α and subunit-ß, albumin, serotransferrin-like, ubiquitin-like, haptoglobin, α-1-antitrypsin-like protein, histone H2B, apolipoprotein A-I, and C3-ß. In contrast, 169 were high-confidence tick-derived proteins. These proteins were classified into six categories based on reported functions in ticks, i.e., enzymes, enzyme inhibitors, transporters, immune-related proteins, muscle proteins, and heat shock proteins. The abundance of Vg, microplusin and α-2-macroglobulin was the highest among tick-derived proteins as indicated by iBAQ. CONCLUSIONS: Numerous tick- and host-derived proteins were identified in hemolymph. The protein profile of H. flava hemolymph revealed a sophisticated protein system in the physiological processes of anticoagulation, digestion of blood meal, and innate immunity. More investigations are needed to characterize tick-derived proteins in hemolymph.

Adenosine A2A Receptor in Bone Marrow-Derived Cells Mediated Macrophages M2 Polarization via PPARγ-P65 Pathway in Chronic Hypoperfusion Situation.

Background: The role of adenosine A2A receptor (A2AR) in the ischemic white matter damage induced by chronic cerebral hypoperfusion remains obscure. Here we investigated the role of A2AR in the process of macrophage polarizations in the white matter damage induced by chronic cerebral hypoperfusion and explored the involved signaling pathways. Methods: We combined mouse model and macrophage cell line for our study. White matter lesions were induced in A2AR knockout mice, wild-type mice, and chimeric mice generated by bone marrow cells transplantation through bilateral common carotid artery stenosis. Microglial/macrophage polarization in the corpus callosum was detected by immunofluorescence. For the cell line experiments, RAW264.7 macrophages were treated with the A2AR agonist CHS21680 or A2AR antagonist SCH58261 for 30 min and cultured under low-glucose and hypoxic conditions. Macrophage polarization was examined by immunofluorescence. The expression of peroxisome proliferator activated receptor gamma (PPARγ) and transcription factor P65 was examined by western blotting and real-time polymerase chain reaction (RT-PCR). Inflammatory cytokine factors were assessed by enzyme-linked immunosorbent assay (ELISA) and RT-PCR. Results: Both global A2AR knockout and inactivation of A2AR in bone marrow-derived cells enhanced M1 marker expression in chronic ischemic white matter lesions. Under low-glucose and hypoxic conditions, CGS21680 treatment promoted macrophage M2 polarization, increased the expression of PPARγ, P65, and interleukin-10 (IL-10) and suppressed the expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). The CGS21680-induced upregulation of P65 and IL-10 was abolished in macrophages upon PPARγ knockdown. The downregulation of TNF-α and IL-1ß by CGS21680 was less affected by PPARγ knockdown. Conclusions: In the cerebral hypoperfusion induced white matter damage, A2AR signaling in bone marrow-derived cells induces macrophage M2 polarization and increases the expression of the anti-inflammatory factor IL-10 via the PPARγ-P65 pathway, both of which might explain its neuroprotective effect.

Observation of the Sedative Effect of Dexmedetomidine Combined With Midazolam Nasal Drops Before a Pediatric Craniocerebral MRI.

OBJECTIVE: This study aimed to investigate the sedative effect of dexmedetomidine combined with midazolam nasal drops before a pediatric craniocerebral magnetic resonance imaging (MRI). METHODS: Eighty children who needed an MRI examination were enrolled in the present study and randomly divided into 2 groups: the observation group (dexmedetomidine combined with midazolam nasal drops) and the control group. After the children were given the medication, their heart rate, blood oxygen saturation (SpO2), and respiratory rate were continuously monitored and the adverse reactions such as nausea and vomiting, cough, restlessness, heart rate slowdown, and respiratory depression were observed. RESULTS: The difference in the onset time between the 2 groups was not statistically significant (P > 0.05), but the duration was significantly longer in the observation group than in the control group (P < 0.01) and the examination success rate were significantly higher in the observation group than in the control group (P < 0.05). CONCLUSION: The protocol of 3 µg/kg of a dexmedetomidine injection combined with 0.3 mg/kg of midazolam nasal drops is safe, easy to operate, and has a high success rate, which is worthy of clinical promotion.

Circular RNA TUBD1 Acts as the miR-146a-5p Sponge to Affect the Viability and Pro-Inflammatory Cytokine Production of LX-2 Cells through the TLR4 Pathway.

The functions and molecular mechanism of circRNAs in the development of radiation-induced liver disease (RILD) remain largely unknown. The goal of this study was to explore the expression and potential role of a new circular RNA, named circTUBD1, in irradiated and lipopolysaccharide (LPS)-stimulated human hepatic stellate cell (HSC) line LX-2 cells. The expression of circTUBD1 was significantly upregulated in irradiated and LPS-stimulated LX-2 cells compared to non-treated LX-2 cells. To explore the functions of circTUBD1, small interfering RNAs targeting circTUBD1 were designed. Silencing circTUBD1 inhibited proliferation, promoted apoptosis of LX-2 cells, and significantly decreased the expression level of pro-inflammatory cytokines, including IL-1ß, IL-6 and TNF-α in irradiated and LPS-stimulated LX-2 cells. Mechanistic analysis suggested that circTUBD1 acted as the miR-146a-5p sponge to affect pro-inflammatory cytokine production through regulating expression of Toll-like receptor 4 (TLR4), interleukin receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor-6 (TRAF6), and phosphorylation of nuclear factor-kappa B (pNF-κB) in irradiated and LPS-stimulated LX-2 cells. To our knowledge, this is the first study to show that circTUBD1 acts as a miR-146a-5p sponge to affect the viability and pro-inflammatory cytokine production of LX-2 cells through the TLR4 pathway, suggesting that circTUBD1 is a potential target for RILD therapy.

MicroRNA-146a-5p Attenuates Fibrosis-related Molecules in Irradiated and TGF-beta1-Treated Human Hepatic Stellate Cells by Regulating PTPRA-SRC Signaling.

MicroRNAs (miRNAs) have been shown to play a pivotal role in the pathogenesis and maintenance of liver fibrosis by altering expression of their downstream target genes. However, their role in radiation-induced liver fibrosis has not been assessed in detail. Here, we investigated the role of miR-146a-5p and the target gene in regulation of fibrosis-related markers in the human hepatic stellate cell line LX2. LX2 cells were stimulated with 8 Gy of X rays and various concentrations of TGF-ß1 (0-5 ng/ml). Expression of α-SMA, collagen 1 and miR-146a-5p was evaluated. The MiR-146a-5p target gene predictions were performed using bioinformatics analysis and confirmed by dual-luciferase reporter experiment. The effect of miR-146a-5p and the involved target gene on the expression of these fibrogenic molecules was also assessed. Expression of α-SMA and collagen 1 were upregulated in response to radiation and/or TGF-ß1 treatment and miR-146a-5p levels were altered in LX2 cells. Restoration of miR-146a-5p expression suppressed expression of α-SMA and collagen 1 in irradiated and TGF-ß1-treated LX2 cells. Subsequent mechanism experiments revealed that miR-146a-5p overexpression inhibited PTPRA expression by binding to its 3'-untrans-lated region and reduced SRC activation. In addition, enhancement of PTPRA partially reversed the suppressive effect of miR-146a-5p on α-SMA and collagen 1 expression in LX2 cells. In conclusion, miR-146a-5p may negatively regulate the PTPRA-SRC signaling to inhibit expression of fibrosis-related markers in irradiated and TGF-ß1-stimulated LX2 cells.

Infiltrating regulatory T cells promote invasiveness of liver cancer cells via inducing epithelial-mesenchymal transition.

BACKGROUND: Regulatory T (Treg) cells are a major component of the microenvironment of hepatocellular carcinoma (HCC) contributing to immunosuppression. The present study aimed to evaluate the effects of Treg cells on the invasion potential of HCC. METHODS: Infiltrating Treg cells were isolated from fresh HCC tissues by immunomagnetic bead separation and detected by flow cytometry. Circulating tumor cells (CTCs) were detected using the CellSearch platform. The cell migration and invasion potentials were evaluated by Transwell assays. The cell viability was tested by the cell counting kit-8 (CCK8) approach, and the apoptosis rates were determined by flow cytometry. The concentrations of active transforming growth factor-ß1 (TGFß1) were measured by enzyme-linked immunosorbent assay. RESULTS: Infiltrating Treg cells significantly correlated with the number of CTCs and vascular invasion (both P<0.05). Moreover, these cells could greatly promote HCC migration, invasion, and proliferation, and inhibit HCC apoptosis. Polymerase chain reaction and Western blot assays revealed that Treg cells significantly decreased the expression levels of epithelium-related molecules and increased the expression levels of mesenchyme-related molecules. Treg cells could activate Smad2/3 via secreting TGFß1, and these effects could be impaired by knocking down the expression of TGFß1 in Treg cells. CONCLUSIONS: The involvement of infiltrating Treg cells in triggering the TGFß1 signaling pathway and promoting the epithelial-mesenchymal transition (EMT) of cancer cells during tumor hematogenous dissemination is presumably responsible for increasing the invasiveness potential of HCC cells. Targeting Treg cells in microenvironments can be a promising therapeutic strategy to improve the prognosis for patients with HCC undergoing resection.

Tetrandrine Enhances Radiosensitization in Human Hepatocellular Carcinoma Cell Lines.

The goal of this study was to determine whether tetrandrine enhanced radiosensitization in different hepatocellular carcinoma cell lines and to elucidate the potential mechanism. We also tested whether PA28γ was regulated by tetrandrine. The human hepatocellular carcinoma cell lines HepG2 and LM3 were divided into six groups: control; low-dosage (0.5 or 5 µg/ml) tetrandrine alone; high-dosage (1.0 or 10 µg/ml) tetrandrine alone; irradiation alone; irradiation with low-dosage (0.5 µg/ml or 5 µg/ml) tetrandrine; and irradiation with high-dosage (1.0 µg/ml or 10 µg/ml) tetrandrine. Colony-forming assays were performed. Expression of cyclin and apoptosis-related proteins, including cyclin B1, phosphorylated cyclin-dependent kinase 1 [phospho-CDC2 (Tyr15)], Bax and caspase-3, as well as PA28γ expression, were evaluated using Western blot analysis. Apoptosis rate and cell cycle distribution were examined using flow cytometry analysis. Tetrandrine enhanced radiosensitivity in HepG2 and LM3 cells, as characterized by a narrower shoulder area and steeper linear area, and the enhanced radiosensitization increased with tetrandrine dosage. After tetrandrine treatment, the apoptosis rate significantly increased, whereas the proportion of cells in the G2 phase dramatically decreased in dose- and time-dependent manners after irradiation. However, the effect of reverse G2 arrest was weaker in p53-mutant cells (LM3 cells). Finally, we observed that tetrandrine downregulated PA28γ expression. Moreover, when PA28γ was downregulated, apoptosis and cell cycle distribution were also altered; however, the effects were weaker in p53-mutant cells. Therefore, we propose that tetrandrine-mediated apoptosis induction and G2 arrest attenuation are at least partly mediated by PA28γ.

Toll-like receptor 4 and its associated proteins as prognostic factors for HCC treated by post-radiotherapy surgery.

Locally advanced hepatocellular carcinoma (HCC) treated by radiotherapy (RT) may be suited for further treatment with surgery. As a critical mediator of the post-RT immune response, Toll-like receptor 4 (TLR4) and its associated proteins may serve as prognostic factors for patients with HCC treated by post-RT surgery. In the present study, a total of 20 patients with HCC treated by post-RT surgery were enrolled. Resected tumor and peritumoral liver tissues were used to construct tissue microarrays that were assessed with immunohistochemical staining for the expression levels of TLR4, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and vascular endothelial growth factor receptor 2 (VEGFR2). The overall (OS) and disease-free (DFS) survival outcomes for each patient were assessed, and the severity of radiation-induced liver diseases (RILDs) was detected. The patients with low TLR4 or TRAIL expression exhibited significantly better OS times than those with high TLR4 (P=0.003) or TRAIL (P=0.007) expression, whereas the median DFS times for patients with low VEGFR2 or TRAIL were significantly longer than those with high VEGFR2 (P=0.003) or TRAIL (P=0.008) expression. No significant differences in OS or DFS times were identified according to the expression of TLR4, VEGFR2 or TRAIL in peritumoral liver tissue, although more severe RILDs were identified in patients with the high expression of these factors in the peritumoral liver tissue post-RT (P<0.05). Therefore, the expression levels of TLR4 and its associated proteins in HCC tumors may be suitable as prognostic factors for patients with HCC treated by post-RT surgery. The inhibition of TLR4, VEGFR2 and TRAIL expression in HCC and non-tumor liver tissue may lessen the severity of RILDs and improve survival outcomes in the future.

Ectopic Suprasellar Thyrotropin-Secreting Pituitary Adenoma: Case Report and Literature Review.

BACKGROUND: Ectopic thyroid-stimulating hormone (TSH)-secreting pituitary adenomas are rare and can often be misdiagnosed as primary hyperthyroidism. We present a case of an ectopic suprasellar TSH-secreting pituitary adenoma. A literature review of previously reported ectopic TSH-secreting and suprasellar pituitary adenomas is included to illustrate the clinical characteristics of this disease entity and the diversity of operative approaches to treating ectopic suprasellar pituitary adenomas. CASE DESCRIPTION: A 46-year-old man presented with typical clinical signs of hyperthyroidism and a history of progressive visual field impairment and vision loss. Laboratory investigations revealed that the patient had elevated levels of free thyroxine and free triiodothyronine and a normal level of TSH. Neuro-ophthalmologic examination showed right eye/left eye = 1.0/0.6 and left temporal hemianopia. Magnetic resonance imaging revealed a mass located in the suprasellar space. The patient underwent preoperative short-term octreotide treatment followed by gross total resection of the tumor via the extended endoscopic endonasal transtuberculum sellar approach. At 6-month follow-up evaluation, the patient's endocrinologic function tests met the criteria for cure, and magnetic resonance imaging revealed a normal pituitary gland and stalk with no tumor recurrence. Histologic diagnosis confirmed the presence of a TSH-secreting pituitary adenoma. CONCLUSIONS: To the best of our knowledge, this is the first reported case of an ectopic suprasellar TSH-secreting pituitary adenoma. Preoperative preparation and complete resection are the keys to a cure. The extended endoscopic endonasal transtuberculum sellar approach is an alternative minimally invasive method for the removal of an ectopic suprasellar pituitary adenoma.

A mouse radiation-induced liver disease model for stereotactic body radiation therapy validated in patients with hepatocellular carcinoma.

PURPOSE: Lower radiation tolerance of the whole liver hinders dose escalations of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) treatment. This study was conducted to define the exact doses that result in radiation-induced liver disease (RILD) as well as to determine dose constraints for the critical organs at risk (OARs) in mice; these parameters are still undefined in HCC SBRT. METHODS: This study consisted of two phases. In the primary phase, mice treated with helical tomotherapy-based SBRT were stratified according to escalating radiation doses to the livers. The pathological differences, signs [such as mouse performance status (MPS)], and serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/albumin levels were observed. Radiation-induced disease severities of the OARs were scored using systematic evaluation standards. In the validation phase in humans, 13 patients with HCC who had undergone radiotherapy before hepatectomy were enrolled to validate RILD pathological changes in a mouse study. RESULTS: The evaluation criteria of the mouse liver radiotherapy-related signs were as follows: MPS ≥ 2.0 ± 0.52, AST/ALT ≥ 589.2 ± 118.5/137.4 ± 15.3 U/L, serum albumin ≤ 16.8 ± 2.29 g/L. The preliminary dose constraints of the OARs were also obtained, such as those for the liver (average dose ≤ 26.36 ± 1.71 Gy) and gastrointestinal tract (maximum dose ≤ 22.63 Gy). Mouse RILD models were able to be developed when the livers were irradiated with average doses of ≥31.76 ± 1.94 Gy (single fraction). RILD pathological changes in mice have also been validated in HCC patients. CONCLUSIONS: Mouse RILD models could be developed with SBRT based on the dose constraints for the OARs and evaluation criteria of mouse liver radiotherapy-related signs, and the authors' results favor the study of further approaches to treat HCC with SBRT.

Effect of reduced x-ray tube voltage, low iodine concentration contrast medium, and sinogram-affirmed iterative reconstruction on image quality and radiation dose at coronary CT angiography: results of the prospective multicenter REALISE trial.

BACKGROUND: Both low tube voltage and sinogram-affirmed iterative reconstruction (IR) techniques hold promise to decrease radiation dose at coronary CT angiography (CCTA). The increased iodine contrast at low tube voltage allows for minimizing iodine load. OBJECTIVE: To assess the effect of reduced x-ray tube voltage, low iodine concentration contrast medium and IR on image quality and radiation dose at CCTA. METHODS: Two hundred thirty-one consecutive patients with suspected coronary artery disease were enrolled in this prospective, multicenter trial and randomized to 1 of 2 dual-source CCTA protocols: 120-kVp with 370 mgI/mL iopromide or iopamidol (n = 116; 44 women; 55.3 ± 9.8 years) or 100 kVp with 270 mgI/mL iodixanol (n = 115; 48 women; 54.2 ± 10.4 years). Reconstruction was performed with filtered back projection and IR. Attenuation, image noise, signal-to-noise ratio, and contrast-to-noise ratio were measured and image quality scored. Size-specific dose estimates and effective doses were calculated. RESULTS: There were no significant differences in mean arterial attenuation (406.6 ± 76.7 vs 409.7 ± 65.2 Hounsfield units; P = .739), image noise (18.7 ± 3.8 vs 17.9 ± 3.4 Hounsfield units; P = .138), signal-to-noise ratio (22.5 ± 5.4 vs 23.7 ± 6.1; P = .126), contrast-to-noise ratio (17.5 ± 5.5 vs 18.3 ± 6.1; P = .286), or image quality scores (4.1 ± 0.9 vs 4.0 ± 0.9; P > .05) between 120-kVp filtered back projection-reconstructed and 100-kVp IR-reconstructed series. Mean iodine dose was 26.5% lower (18.3 ± 0.5 vs 24.9 ± 0.9 g; P < .0001), mean size-specific dose estimate was 35.1% lower (17.9 ± 6.6 vs 27.5 ± 8.2 mGy; P < .0001), and effective dose was 34.9% lower (2.3 ± 1.0 vs 3.5 ± 1.1 mSv; P < .0001) with the 100 kVp compared with the 120-kVp protocol, respectively. CONCLUSION: Using low x-ray tube voltage and IR allows for decreasing the iodine load and effective radiation dose at CCTA while maintaining image quality.

Radiotherapy treatment of adrenal gland metastases from hepatocellular carcinoma: clinical features and prognostic factors.

BACKGROUND: The optimal treatment for adrenal metastases from hepatocellular carcinoma (HCC) has not been established. This study analyzed the effects of radiation therapy (RT) for such metastases and identified clinical features and predictors of survival in these patients. METHODS: We retrospectively investigated 55 patients with adrenal metastasis from HCC who had been treated with RT. Radiation doses to the adrenal lesions ranged from 26 to 60 Gy, while the intrahepatic lesions were treated by surgical resection, transarterial chemoembolization (TACE), liver transplantation, and/or RT. RT was conducted to adrenal lesions after their intrahepatic lesions were controlled more than 2 months. The parameters studied included survival rates and tumor responses to RT. The Kaplan-Meier method was used to evaluate survival rate and the Cox regression model was used to identify potential predictors of outcome. RESULTS: The patients treated by RT had adrenal metastasis on the right side (41), the left (6), or on both sides (8). In all 55 patients, the median survival duration was 13.6 months and there was 100% pain relief after completion of RT. Adverse effects were mild to moderate. Unfavorable pretreatment predictors determined by univariate analysis were associated with multiple intrahepatic foci, metastases to additional organs, high γ-glutamyltransferase and alpha-fetoprotein levels, liver function of Child-Pugh classification B and uncontrolled primary HCC. By multivariate analysis, unfavorable predictors were multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC. CONCLUSIONS: Radiotherapy as treatment for adrenal metastases in HCC is a good palliative therapy that is associated with reasonable safety. It appears reasonable that such patients should be considered to be treated with radiotherapy. Multiple intrahepatic foci, metastases to additional organs and uncontrolled primary HCC were unfavorable predictors.

TLR4-dependant immune response, but not hepatitis B virus reactivation, is important in radiation-induced liver disease of liver cancer radiotherapy.

Toll-like receptor 4 (TLR4) is an important trigger of the immune response against hepatitis B virus (HBV) infection and liver injuries. The roles of HBV reactivation versus TLR4-dependant immune response may be critical factors in preventing radiation-induced liver diseases (RILDs) after liver cancer radiotherapy. This study consists of three phases. In the primary phase, livers of mutant TLR4 (TLR4(-)) mice were irradiated with 30 Gy in either the absence or presence of HBV infection. The latter was done by introduction of plasmid pAAV/HBV 1.2. In the advanced phase, RILDs were compared in normal TLR4 (TLR4(+)) versus TLR4(-) mice. In the validation phase, 28 liver cancer patients who had undergone radiotherapy before hepatectomy were enrolled. Liver biopsies near tumors, irradiated with 35-48 Gy, were used to construct tissue microarrays. HBV reactivation, TLR4 expression, and severity of RILDs were studied in both mouse and human. More HBV reactivation, without significant RILD, was observed in irradiated versus unirradiated TLR4(-) mice. RILD scores of TLR4(+) mice were higher than TLR4(-) mice. In humans, serious RILDs tended to develop in patients with high TLR4 expression, but not in patients with low TLR4 or high HBV surface antigen expression. High TLR4 expression was seen in only 2 of 12 HBV-reactive patients, but in HBV-nonreactive patients, it was seen in 6 of 9 (P < 0.03). In summary, RILDs correlated with high TLR4 expression, but not with HBV reactivation, which is inhibited in liver with high TLR4 expression after liver cancer radiotherapy.

[Pharmacokinetics of genistein in urine of healthy volunteers].

In order to study the excretion of genistein (GEN) capsule, an estrogen drugs, in human, 30 healthy volunteers were selected and orally administered 50, 100, and 300 mg genistein in an parallel study. Genistein were determined in urine by LC-MS/MS and glucuronidated genistein (GENG) were indirectly determined with enzymatic hydrolysis in urine by LC-MS/MS, and the pharmacokinetic parameters were analyzed by DAS software (ver 2.0). The result showed that the concentrations of genistein in human urine were less than 1% of the GENG, and the cumulative excretion of GEN in 48 h were 0.037, 0.134, and 0.142 mg, separately, and the urinary excretion percentage were only 0.07%, 0.13%, and 0.05%, separately. But the cumulative excretion of GENG in 48 h was 5.3, 13.8, and 15.4 mg, separately, and the urinary excretion percentage were 10.6%, 13.8%, and 5.1%, separately, and the max urinary excretive rate was 0.4, 1.0, and 1.4 mg x h(-1), separately (tmax were 6 h). Studies showed that part of drug excreted through kidney in a form of GENG in human, and the cumulative urinary excretion and the maximum excretion rate of GENG showed a proportional increase conditioned with the dose in the range of 50-100 mg, but showed non-linear increase feature in 300 mg.

Enhanced production of CTGF and IL-11 from highly metastatic hepatoma cells under hypoxic conditions: an implication of hepatocellular carcinoma metastasis to bone.

PURPOSE: The biology underlying bone-specific metastasis (BM) of hepatocellular carcinoma (HCC) is poorly understood. The goal of the present study is to further elucidate the molecular and cellular mechanisms underlying HCC with BM. METHODS: The expression of connective tissue growth factor (CTGF) and interleukin-11 (IL-11) in RNA extracted from 127 formalin-fixed, paraffin-embedded HCC specimens was examined by quantitative real-time polymerase chain reaction. A cellular hypoxic model was established in vitro to investigate CTGF and osteoprotegerin (OPG) expression and roles in hypoxia-induced tumor aggressiveness. RESULTS: The mean CTGF expression in BM versus non-metastatic samples was 3.63-times higher, and IL-11 expression was detected in 62.5 % (10/16) of BM samples versus only in 18.9 % (21/111) of the non-metastatic ones. Highly metastatic HCC cell lines tended to show strong expression of CTGF and IL-11, but low expression of OPG. Hypoxic stimulation of HCC 97L cells increased the level of CTGF mRNA by 2.80-fold within 1.5 h, and hypoxia-inducible factor-1α mRNA levels in these cells could be increased by stimulation with recombinant CTGF protein. Furthermore, OPG and matrix metalloproteinase-2 and -9 levels were also induced under hypoxic conditions. CONCLUSIONS: Expression levels of intratumoral CTGF or IL-11 were independent prognostic factors for the development of BM in HCC patients. Tumor hypoxia enhanced the expression of CTGF, which initiates the invasive angiogenesis cascade and enhances expression of many hypoxia-associated genes. Cellular release of OPG may play a role in tumor cell survival. The hypoxia-induced cascade in HCC cells may contribute to invasion and metastasis in vivo.

Role of AC-cAMP-PKA Cascade in Antidepressant Action of Electroacupuncture Treatment in Rats.

Adenylyl cyclase (AC)-cyclic adenosine monophosphate (cAMP)-cAMP-dependent protein kinase A (PKA) cascade is considered to be associated with the pathogenesis and treatment of depression. The present study was conducted to explore the role of the cAMP cascade in antidepressant action of electroacupuncture (EA) treatment for chronic mild stress (CMS)-induced depression model rats. The results showed that EA improved significantly behavior symptoms in depression and dysfunction of AC-cAMP-PKA signal transduction pathway induced by CMS, which was as effective as fluoxetine. Moreover, the antidepressant effects of EA rather than Fluoxetine were completely abolished by H89, a specific PKA inhibitor. Consequently, EA has a significant antidepressant treatment in CMS-induced depression model rats, and AC-cAMP-PKA signal transduction pathway is crucial for it.