Cross-modality supervised image restoration enables nanoscale tracking of synaptic plasticity in living mice.

Learning is thought to involve changes in glutamate receptors at synapses, submicron structures that mediate communication between neurons in the central nervous system. Due to their small size and high density, synapses are difficult to resolve in vivo, limiting our ability to directly relate receptor dynamics to animal behavior. Here we developed a combination of computational and biological methods to overcome these challenges. First, we trained a deep-learning image-restoration algorithm that combines the advantages of ex vivo super-resolution and in vivo imaging modalities to overcome limitations specific to each optical system. When applied to in vivo images from transgenic mice expressing fluorescently labeled glutamate receptors, this restoration algorithm super-resolved synapses, enabling the tracking of behavior-associated synaptic plasticity with high spatial resolution. This method demonstrates the capabilities of image enhancement to learn from ex vivo data and imaging techniques to improve in vivo imaging resolution.

Ceramic-metal composites for heat exchangers in concentrated solar power plants.

The efficiency of generating electricity from heat using concentrated solar power plants (which use mirrors or lenses to concentrate sunlight in order to drive heat engines, usually involving turbines) may be appreciably increased by operating with higher turbine inlet temperatures, but this would require improved heat exchanger materials. By operating turbines with inlet temperatures above 1,023 kelvin using closed-cycle high-pressure supercritical carbon dioxide (sCO2) recompression cycles, instead of using conventional (such as subcritical steam Rankine) cycles with inlet temperatures below 823 kelvin1-3, the relative heat-to-electricity conversion efficiency may be increased by more than 20 per cent. The resulting reduction in the cost of dispatchable electricity from concentrated solar power plants (coupled with thermal energy storage4-6) would be an important step towards direct competition with fossil-fuel-based plants and a large reduction in greenhouse gas emissions7. However, the inlet temperatures of closed-cycle high-pressure sCO2 turbine systems are limited8 by the thermomechanical performance of the compact, metal-alloy-based, printed-circuit-type heat exchangers used to transfer heat to sCO2. Here we present a robust composite of ceramic (zirconium carbide, ZrC) and the refractory metal tungsten (W) for use in printed-circuit-type heat exchangers at temperatures above 1,023 kelvin9. This composite has attractive high-temperature thermal, mechanical and chemical properties and can be processed in a cost-effective manner. We fabricated ZrC/W-based heat exchanger plates with tunable channel patterns by the shape-and-size-preserving chemical conversion of porous tungsten carbide plates. The dense ZrC/W-based composites exhibited failure strengths of over 350 megapascals at 1,073 kelvin, and thermal conductivity values two to three times greater than those of iron- or nickel-based alloys at this temperature. Corrosion resistance to sCO2 at 1,023 kelvin and 20 megapascals was achieved10 by bonding a copper layer to the composite surface and adding 50 parts per million carbon monoxide to sCO2. Techno-economic analyses indicate that ZrC/W-based heat exchangers can strongly outperform nickel-superalloy-based printed-circuit heat exchangers at lower cost.

pHERV-W envelope protein fuels microglial cell-dependent damage of myelinated axons in multiple sclerosis.

Axonal degeneration is central to clinical disability and disease progression in multiple sclerosis (MS). Myeloid cells such as brain-resident microglia and blood-borne monocytes are thought to be critically involved in this degenerative process. However, the exact underlying mechanisms have still not been clarified. We have previously demonstrated that human endogenous retrovirus type W (HERV-W) negatively affects oligodendroglial precursor cell (OPC) differentiation and remyelination via its envelope protein pathogenic HERV-W (pHERV-W) ENV (formerly MS-associated retrovirus [MSRV]-ENV). In this current study, we investigated whether pHERV-W ENV also plays a role in axonal injury in MS. We found that in MS lesions, pHERV-W ENV is present in myeloid cells associated with axons. Focusing on progressive disease stages, we could then demonstrate that pHERV-W ENV induces a degenerative phenotype in microglial cells, driving them toward a close spatial association with myelinated axons. Moreover, in pHERV-W ENV-stimulated myelinated cocultures, microglia were found to structurally damage myelinated axons. Taken together, our data suggest that pHERV-W ENV-mediated microglial polarization contributes to neurodegeneration in MS. Thus, this analysis provides a neurobiological rationale for a recently completed clinical study in MS patients showing that antibody-mediated neutralization of pHERV-W ENV exerts neuroprotective effects.

3-Dimensional Immunostaining and Automated Deep-Learning Based Analysis of Nerve Degeneration.

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease driven by inflammation and demyelination in the brain, spinal cord, and optic nerve. Optic neuritis, characterized by inflammation and demyelination of the optic nerve, is a symptom in many patients with MS. The optic nerve is the highway for visual information transmitted from the retina to the brain. It contains axons from the retinal ganglion cells (RGCs) that reside in the retina, myelin forming oligodendrocytes and resident microglia and astrocytes. Inflammation, demyelination, and axonal degeneration are also present in the optic nerve of mice subjected to experimental autoimmune encephalomyelitis (EAE), a preclinical mouse model of MS. Monitoring the optic nerve in EAE is a useful strategy to study the presentation and progression of pathology in the visual system; however, current approaches have relied on sectioning, staining and manual quantification. Further, information regarding the spatial load of lesions and inflammation is dependent on the area of sectioning. To better characterize cellular pathology in the EAE model, we employed a tissue clearing and 3D immunolabelling and imaging protocol to observe patterns of immune cell infiltration and activation throughout the optic nerve. Increased density of TOPRO staining for nuclei captured immune cell infiltration and Iba1 immunostaining was employed to monitor microglia and macrophages. Axonal degeneration was monitored by neurofilament immunolabelling to reveal axonal swellings throughout the optic nerve. In parallel, we developed a convolutional neural network with a UNet architecture (CNN-UNet) called BlebNet for automated identification and quantification of axonal swellings in whole mount optic nerves. Together this constitutes a toolkit for 3-dimensional immunostaining to monitor general optic nerve pathology and fast automated quantification of axonal defects that could also be adapted to monitor axonal degeneration and inflammation in other neurodegenerative disease models.

Familial risk for endometriosis and its interaction with smoking, age at menarche and body mass index: a population-based cohort study among siblings.

OBJECTIVE: To quantify familial risk of endometriosis among full siblings and examine interactions between family history and smoking, age at menarche or body mass index (BMI). DESIGN, SETTING AND POPULATION: Population-based nationwide cohort study. METHODS: Using data from the Korean National Health Insurance and Screening Programme databases on kinship, healthcare utilisation, lifestyle and anthropometrics, we identified 2 109 288 women with full siblings and their environmental risk factors from 2002 to 2018. Familial risks were estimated using Cox proportional-hazards models, represented as incidence risk ratios (IRR) with 95% CI. Interaction between family history and smoking, age at menarche or BMI were assessed on an additive scale. MAIN OUTCOME MEASURES: IRR of endometriosis among women with and without affected siblings. RESULTS: From 19 195 women with affected siblings, 1126 developed endometriosis with an incidence of 35.45/10 000 person-years. Familial risk of endometriosis with versus without affected siblings was increased to IRR 2.75 (95% CI 2.25-3.36), and the highest risk was with affected twins (IRR 6.98; 95% CI 4.19-11.62). Women with both a family history and either smoking, early menarche or low BMI had a significantly higher risk of endometriosis compared with the general population and can be regarded as a high-risk group, the IRRs were 4.28 (95% CI 2.43-7.55), 3.47 (95% CI 2.82-4.26) and 3.09 (95% CI 2.68-3.56), respectively. Substantial effect modification of the associations was noted by smoking and early menarche, as their combined risk with family history exceeded the sum of their individual risks, which was also statistically significant. CONCLUSION: Genetic factors are the primary contributor to the familial aggregation of endometriosis. Significant gene-environment interaction exists between family history and smoking or early menarche. TWEETABLE ABSTRACT: Significant gene-environment interaction exists between family history of endometriosis and smoking or early menarche.

Neodymium (Nd) based oxide perovskite nanostructures for photocatalytic and photoelectrochemical water splitting functions.

Neodymium (Nd) based perovskite (Nd1-xCoxFeO3) nanostructures were processed to address the rising energy and environment crisis through offering solutions by photocatalytic and photoelectrochemical (PEC) water splitting reactions. The impact of cobalt (Co) ions on the physicochemical properties of Nd-perovskites were studied using X-ray diffraction (XRD), Raman and electron microscopic instruments. The interaction of metal ions was studied in depth via X-ray photoelectron spectroscopy (XPS). Absorption and photoluminescence signals inferred the optical band gap to be lowered and defect states to increase upon Co substitution. Improved photocatalytic efficacy in Nd1-xCoxFeO3 was evaluated by comparative studies using NdFeO3. Secondly, the enhanced conductivities in Nd1-xCoxFeO3 studied via Nyquist plot was found to be advantageous in photoelectrode fabrication for PEC functions. Time-dependent photocurrent density results affirmed the stability in processed devices. Co ions were also inferred to boost the separation of charge carriers effectively. The improved performance in Nd1-xCoxFeO3 nanostructures were well justified to the successful incorporation of Co ions that sway the Nd-O, Co-O and Co-Fe-O bondings and boost the photon absorption and electronic conductivity to facilitate the observed performance.

Extrinsic immune cell-derived, but not intrinsic oligodendroglial factors contribute to oligodendroglial differentiation block in multiple sclerosis.

Multiple sclerosis (MS) is the most frequent demyelinating disease in young adults and despite significant advances in immunotherapy, disease progression still cannot be prevented. Promotion of remyelination, an endogenous repair mechanism resulting in the formation of new myelin sheaths around demyelinated axons, represents a promising new treatment approach. However, remyelination frequently fails in MS lesions, which can in part be attributed to impaired differentiation of oligodendroglial progenitor cells into mature, myelinating oligodendrocytes. The reasons for impaired oligodendroglial differentiation and defective remyelination in MS are currently unknown. To determine whether intrinsic oligodendroglial factors contribute to impaired remyelination in relapsing-remitting MS (RRMS), we compared induced pluripotent stem cell-derived oligodendrocytes (hiOL) from RRMS patients and controls, among them two monozygous twin pairs discordant for MS. We found that hiOL from RRMS patients and controls were virtually indistinguishable with respect to remyelination-associated functions and proteomic composition. However, while analyzing the effect of extrinsic factors we discovered that supernatants of activated peripheral blood mononuclear cells (PBMCs) significantly inhibit oligodendroglial differentiation. In particular, we identified CD4+ T cells as mediators of impaired oligodendroglial differentiation; at least partly due to interferon-gamma secretion. Additionally, we observed that blocked oligodendroglial differentiation induced by PBMC supernatants could not be restored by application of oligodendroglial differentiation promoting drugs, whereas treatment of PBMCs with the immunomodulatory drug teriflunomide prior to supernatant collection partly rescued oligodendroglial differentiation. In summary, these data indicate that the oligodendroglial differentiation block is not due to intrinsic oligodendroglial factors but rather caused by the inflammatory environment in RRMS lesions which underlines the need for drug screening approaches taking the inflammatory environment into account. Combined, these findings may contribute to the development of new remyelination promoting strategies.

The incidence and survival of melanoma and nonmelanoma skin cancer in patients with vitiligo: a nationwide population-based matched cohort study in Korea.

BACKGROUND: While studies report a lower incidence of skin cancer in white patients with vitiligo compared with controls, the skin cancer incidence in Asian patients with vitiligo is unknown. OBJECTIVES: To quantify the incidence of melanoma and nonmelanoma skin cancer (NMSC) in Korean patients with vitiligo and compare it with matched nonvitiligo controls. METHODS: A retrospective matched cohort study was performed with 131 245 incident vitiligo cases and 2 624 900 age- and sex-matched (1 : 20) controls at index date, who were selected from the Korean National Health Insurance database between January 2005 and December 2017. Stratified Cox proportional hazards regression (stratified by sex, birth year and index year) was used to calculate the hazard ratio (HR) of skin cancer in patients with vitiligo. RESULTS: Patients with vitiligo were followed up for a mean duration of 6·34 years compared with a follow-up period of 6·27 years for matched controls. Ultraviolet (UV) treatment-adjusted HR for melanoma in patients with vitiligo was 3·32 [95% confidence interval (CI) 2·29-4·81] and 1·29 (95% CI 1·06-1·56) for NMSC. The HRs for melanoma and NMSC in the vitiligo population without a history of UV treatment were 3·37 (95% CI 2·32-4·90) and 1·35 (95% CI 1·11-1·64), respectively. CONCLUSIONS: In contrast to white patients with vitiligo, the risk of skin cancer was increased in the Korean vitiligo population. However, it is noteworthy that the skin cancer incidence in Korean patients with vitiligo was lower than that of their white counterparts. Owing to possible ethnic differences in the susceptibility to skin cancer, skin cancer surveillance in the vitiligo population may be adjusted for race. What's already known about this topic? Prior studies have reported a lower incidence of melanoma and nonmelanoma skin cancer (NMSC) in white patients with vitiligo compared with nonvitiligo controls. The skin cancer incidence in Asian patients with vitiligo is unknown. What does this study add? In contrast to white patients, the risk of both melanoma and NMSC was increased in Korean patients with vitiligo compared with controls. Owing to possible ethnic differences in susceptibility to skin cancer, skin cancer surveillance in the vitiligo population should be adjusted for race.

Incidence, survival, and risk of cardiovascular events in adult inflammatory myopathies in South Korea: a nationwide population-based study.

OBJECTIVE: Epidemiological studies on inflammatory myopathies (IMs) show widely variable results, and studies on Asians are lacking. Despite emerging interest in the cardiovascular disease (CVD) risk associated with IMs, the prevalence of CVD in IM patients and its impact on mortality remain unclear. We conducted a nationwide, population-based study on the incidence, mortality, and associated major CVD events of IMs in the Republic of Korea over 11 years. METHOD: Using the nationwide, population-based National Health Insurance claims database and the Rare Intractable Disease registration programme, we estimated incidence, mortality, and CVD occurrence. Survival was examined using the Kaplan-Meier method. Mortality rate in IMs with CVD was analysed by Cox proportional hazards regression. RESULTS: There were 3014 incident cases, 640 of whom died during the study period. The mean annual incidence was 7.16/106. Dermatomyositis (DM) and polymyositis (PM) had 5 year survival rates of 76.8% and 79.3%, respectively. Cardiovascular events occurred in 155 patients and 40.6% of IM patients with CVD died. Acute myocardial infarction in men had the highest risk of any CVD event in both DM [standardized incidence ratio (SIR) 4.2, 95% confidence interval (95% CI) 2.4-7.2] and PM (SIR 3.5, 95% CI 1.8-7.0). Haemorrhagic stroke had the highest hazard ratio (HR) in both DM (HR 2.31, 95% CI 1.13-4.70) and PM patients (HR 2.10, 95% CI 1.03-4.27) compared with the general population with CVD. CONCLUSION: We found persistently low incidence, poor survival, and high major CVD incidence in IMs, and increased mortality in IMs with CVD.

[Expression and significance of PD-1 and PD-L1 in the specimens of epithelial ovarian cancer].

Objective: To examine the expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) in epithelial ovarian cancer (EOC) tissues, and investigate the correlation among their expression, clinicopathological features and prognosis. Methods: The specimens of 180 patients with EOC treated in the First Affiliated Hospital of Dalian Medical University from October 2002 to December 2013 were confirmed by pathological examination. The pathological tissue specimens of subtypes ，included 120 cases of serous carcinoma, 30 cases of mucinous carcinoma, 20 cases of endometrioid carcinoma, and 20 cases of clear cell carcinoma. The normal paracancerous tissues of 50 cases randomly selected from the 180 patients as control group. Immunohistochemical SP method was used to detect the expressions of both PD-1 and PD-L1 in epithelial ovarian cancer tissues, and the relationships among their expressions,the clinicopathological parameters and prognosis were respectively analyzed. Results: （1） PD-1 was expressed in lymphocytes infiltrated in EOC tissues, and PD-L1 was expressed in the cell membranes of cancer tissues. In all EOC cases, 33 cases (18.3%, 33/180) of both PD-1 and PD-L1 were highly expressed, and only 1 (2.0%, 1/50) of control group showed high expression. There was statistically significant difference between two groups (P<0.01). (2) Among the four subtypes tissue specimens of EOC, the high expression rate of PD-1 was 25.0% (30/120) for serous carcinoma, 3/15 for endometrioid carcinoma, 0 (0/30) for mucinous carcinoma, and 0 (0/15) for clear cell carcinoma. The high expression rate of PD-L1 was 23.3% (28/120) for serous carcinoma, 3.3% (1/30) for mucinous carcinoma, 2/15 for endometrioid carcinoma, and 2/15 for clear cell carcinoma. Both PD-1 and PD-L1 expressions in the four sub-types of tissue specimens were significantly different (P<0.05). The high expression rate of both PD-1 and PD-L1 was 9.2% (8/87) in the early stage and 26.9% (25/93) in the late stage. There was a statistically significant difference between the two groups (P<0.01). Similarly, the expression of both PD-1 and PD-L1 were significantly higher in the cases of high-grade EOC （type Ⅱ） than those of low-grade （type Ⅰ） and in the cases of EOC distributed bilaterally than that distributed unilaterally, and there were statistically significant differences (P<0.05). (3) The Kaplan-Meier survival analysis showed that the survival time were respectively 35 and 36 months in the cases with high expressions of both PD-1 and PD-L1, and the survival time were the same as 61 months in the cases with low expression of both PD-1 and PD-L1, and the comparison was statistically significant (P<0.05). Conclusions: The expression levels of PD-1 and PD-L1 in EOC tissues are higher than those in adjacent tissues, especially in serous carcinomas. The expression of both PD-1 and PD-L1 is higher in specimens of the patients with advanced stages. The results showed that the high expression of both PD-1 and PD-L1 is an indicator of poor prognosis of patients suffering from EOC.

Landscape of Elderly Suicide in South Korea: Its Trend According to Age, Gender, and Educational Attainment.

South Korea has one of the highest suicide rates in the world, and the most alarming suicide rate is among its elders. This study aims to understand the social, historical, and cultural context of the Korean older adults and examine suicide trends based on that understanding. The results show that the suicide risk increases with age, the male suicide rate outweighs that of females, and the suicide rate decreases with educational attainment. In addition, several suggestions for reducing elderly suicide rate are addressed, including differentiating the existing social services for elders by age and expanding suicide prevention programs beyond schools to communities so that all people in need can access them.

Questionable correlation of the apparent diffusion coefficient with the histological grade and microvascular invasion in small hepatocellular carcinoma.

AIM: To evaluate the correlation between the apparent diffusion coefficient (ADC) and various histopathological parameters in small hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: In 143 surgically resected small HCCs, the mean and minimum ADC values, tumour-to-liver ADC ratio, and normalised ADC (ADC of the HCC/ADC of the spleen) were correlated to the tumour grade, microvascular invasion (MVI), cellularity, fatty change, degree of fibrosis, and lymphocytic infiltration using linear regression analysis, the Wilcoxon rank sum test, or Spearman's rank correlation. RESULTS: No significant correlation was found between the ADC parameters and tumour grade. In the univariate analysis, the ADC ratio of the tumour was significantly correlated with MVI as well as the degree of fibrosis and lymphocyte infiltration of the HCC (p=0.017, 0.042, and 0.002, respectively). The ADC of the tumour was significantly correlated with the degree of lymphocyte infiltration of the HCC (p=0.049). In the multivariate analysis, the ADC ratio of the tumour was an independent parameter for MVI and the degree of lymphocyte infiltration of the HCC (p=0.034 and <0.001, respectively), and the ADC of the tumour was an independent parameter for the degree of lymphocyte infiltration of the HCC (p=0.009). There was no significant correlation between the other ADCs and pathological tumour parameters. CONCLUSION: The tumour grade of small HCCs was not correlated with ADC parameters. The tumour-to-liver ADC ratio was a significant independent parameter for the degree of lymphocyte infiltration and MVI of small HCCs.

Intranasal inoculation of recombinant DNA vaccine ABA392 against haemorrhagic septicaemia disease.

We evaluate the efficacy of recombinant DNA vaccine ABA392 against haemorrhagic septicaemia infection through intranasal administration route by targeting the mucosal immunity. The DNA vaccine was constructed and subjected to animal study using the Sprague Dawley (SD) rat. The study was divided into two major parts: (i) active and (ii) passive immunization studies, involving 30 animals for each part. Each group was then divided into five test groups: two test samples G1 and G2 with 50 and 100 µg ml-1 purified DNA vaccine; one positive control G5 with 106  CFU per ml formalin-killed PMB2; and two negative controls, G3 and G4 with normal saline and pVAX1 vector. Both studies were conducted for the determination of immunogenicity by total white blood cell count (TWBC), indirect ELISA and histopathological changes for the presence of the bronchus-associated lymphoid tissue (BALT). Our findings demonstrate that TWBC, IgA and IgG increased after each of the three vaccination regimes: groups G1, G2 and G5. Test samples G1 and G2 showed significant differences (P < 0·05) compared to the negative controls, G3 and G4, but no significant differences from the positive control G5. Groups G1, G2 and G5 showed more formation of BALT compared to the negative controls, G3 and G4. Our results show that intranasal inoculation of recombinant DNA vaccine ABA392 can provoke mucosal immunity which makes it a potential prophylactic against HS. SIGNIFICANCE AND IMPACT OF THE STUDY: New approach of combating haemorrhagic septicaemia disease among bovines by recombinant DNA vaccine is crucial to overcome the loss of edible products from the infected bovines. DNA vaccine can potentially serve as a better immunogen which would elicit both cellular and humoral immunity, and it is also stable for its molecular reproduction. This research report demonstrates an effective yet simple way of administering the DNA vaccine via the intranasal route in rats, to provoke the mucosal immunity through the development of immunoglobulins IgA, IgG and bronchus-associated lymphoid tissue which guard as the first-line defence at the host's mucosal lining.

Evaluation of cockerel spermatozoa viability and motility by a novel enzyme based cell viability assay.

1. The results of spermatozoa assessment by the WST-8 (2-[2-methoxy-4-nitrophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H-tetrazolium, monosodium salt) assay, flow cytometry (FC) or computer-assisted sperm analysis (CASA) were compared. 2. Different live/killed ratios of cockerel semen were serially diluted to 120, 60, and 30 × 106 cells/ml, and each sample was analysed by (1) WST-8 assay at 0, 10, 20, 30, 40, 50, 60 min, (2) viability with FC, and (3) motility with CASA. 3. The WST-8 reduction rate was closely correlated with spermatozoa viability and motility. The optimal semen concentration for the WST-8 assay was 120 × 106 cells/ml, and the standard curves for spermatozoa viability and motility predictions, respectively, were yviability60 = 162.8x + 104.96 (R2 = 0.9594) after 60 min of incubation and ymotility40 = 225.09x + 96.299 (R2 = 0.8475) after 40 min of incubation. 4. It was concluded that the WST-8 assay is useful for the practical evaluation of cockerel spermatozoa viability and motility. Compared to FC and CASA, the WST-8 assay does not require expensive and complex instrumentation in the lab. Furthermore, one well of the WST-8 reaction can be used to predict spermatozoa viability and motility at the same time, which all lead it to be efficient and economical for semen quality assessment.

[Expression and significance of MAPK/ERK in the specimens and cells of epithelial ovarian cancer].

Objective: To detect phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) protein expression in epithelial ovarian cancer and cell lines, and to examine the effects of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor AZD6244 on cell proliferation, apoptosis as well as cell cycle of ovarian cancer cells. To explore the function and significance of MAPK/extracellular signal-regulated kinase (ERK) signaling pathway in the development of ovarian cancer. Methods: (1) A total of 104 cases of patients with ovarian cancer who accepted the treatment of gynecological surgery and being confirmed by pathological examination in First Affiliated Hospital, Dalian Medical University from January 2004 to December 2013 were selected. The expressions of p-ERK1/2 protein were detected by immunohistochemistry in ovarian cancer specimens, and the relationship between the expressions of p-ERK1/2 and the clinical features of patients was analyzed. (2) p-ERK1/2 and other related proteins were determined by western blot in various ovarian cancer cells, including SKOV3, OV2008, C13, A2780S, A2780CP, OVCAR4, OVCAR5, OVCAR8 and CAOV3 treated with or without MEK inhibitor. The cellular proliferation, apoptosis and cell cycle of ovarian cancer cells after treatment with MEK inhibitor were analyzed by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Results: (1) The immunohistochemical method showed that p-ERK1/2 between low grade serous carcinoma and clear cell carcinoma were not significantly higher expressed (P>0.05) . However, a lower level of the p-ERK1/2 expression were observed among high grade serous carcinoma, mucinous carcinoma and endometrioid carcinoma (all P<0.05) . There was no significant correlation between the protein expression of p-ERK1/2 and patients' age, pathological stage of surgery, and preoperative serum CA(125) level (P>0.05). (2) Western blot showed that the protein p-ERK1/2 was widely expressed in various ovarian cancer cell lines such as SKOV3, OV2008, C13, A2780S, A2780CP, OVCAR4, OVCAR5, OVCAR8 and CAOV3. After treatment with AZD6244 (5, 10 µmol/L), the level of p-ERK1/2 in OVCAR5 and OVCAR8 decreased significantly in dose-dependent manner. Additionally, we found a reduction of the expression level of cyclin D1, caspase-3 and appeared cleaved poly adenosine diphosphate ribose polymerase (PARP) in OVCAR5 and OVCAR8, compared with control groups. MTT assays showed that OVCAR5, OVCAR8 and A2780S were differently inhibited in the dose-dependent manner after being treated with different concentrations of AZD6244 (0, 2.5, 5, 10, 25, 50 and 100 µmol/L, all P<0.05). Further tested by flow cytometry, the results showed that AZD6244 (5, 10 µmol/L) was able to induce the apoptosis of OVCAR5, OVCAR8 and A2780S, as well as G(0)/G(1) phase arrest, both in a dose-dependent manner (P<0.05). Conclusions: As the main active and functional unit of MAPK/ERK signaling pathway, p-ERK1/2 protein is expressed in both the tissues and various ovarian cancer cell lines. AZD6244 could down-regulated the expression of p-ERK1/2 in ovarian cancer cells, accompanied by the decreased proliferation and increased cell apoptosis of ovarian cancer cells. In conclusion, MAPK/ERK signaling pathway might play a role in the development and progression of ovarian cancer, and may be provide a novel option for molecular targeted therapies of the disease.

Integration of different criteria for borderline resectable pancreatic cancer using classification tree analysis: the use of radiological tumour-vascular interface in correlation with surgical and pathological outcomes.

AIM: To integrate various criteria for borderline resectable pancreatic cancer (BRPC) based on radiological parameters using classification tree analysis. MATERIALS AND METHODS: The institutional review board approved this retrospective study and waived the requirement for informed consent. Two hundred and thirty-five tumour-vein interfaces and 67 tumour-artery interfaces in 245 patients with surgically confirmed pancreatic ductal adenocarcinoma who underwent both preoperative computed tomography (CT) and magnetic resonance imaging (MRI) were assessed by two independent readers. Radiological parameters for evaluation of the tumour-vascular interface were boundary, length of interface, degree of circumferential interface, and contour deformity of affected vessels. Classification tree analysis was performed to determine parameters associated with vascular invasion using pathological and surgical results as the reference standard. RESULTS: In the classification tree analysis for the tumour-vein interface, contour deformity and degree of circumferential interface were the first and second determining factors, respectively, for both surgical and pathological vascular invasion. For the tumour-artery interface, boundary and degree of circumferential interface were the first and second determining factors for surgical invasion, while contour deformity and length of interface were the first and second determining factors for pathological invasion. The BRPC group of modified criteria arbitrarily formed based on the results had similar surgical (74.1-81.6%) and pathological (54.3-63.3%) venous invasion compared to that of the National Comprehensive Cancer Network (NCCN) criteria, and the lowest surgical (33.3%) and pathological (6.7%) arterial invasion compared with those in previously established criteria for BRPC (43.3-55.6% and 22.2-26.1%, respectively). CONCLUSION: Various criteria for BRPCs were integrated using classification tree analysis, and a modified criterion for BRPC, which provides satisfactory results, was established.

Initial radiofrequency ablation failure for hepatocellular carcinoma: repeated radiofrequency ablation versus transarterial chemoembolisation.

AIM: To compare the long-term therapeutic outcomes of repeated radiofrequency ablation (RFA) with that of transarterial chemoembolisation (TACE) in patients with local tumour progression (LTP) after initial RFA treatment for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. Between July 2006 and February 2012, 713 patients underwent RFA for single HCC as a first-line treatment. Fifty-eight patients who showed LTP as initial tumour recurrence post-RFA treatment were included. Patients were treated with either repeated RFA (n=33) or TACE (n=25). TACE was performed as an alternative therapeutic option when repeated RFA was not feasible based on the planning ultrasonography. Recurrence-free and overall survival rates were estimated using the Kaplan-Meier method. Prognostic factors for outcomes were evaluated using the Cox proportional hazards model. RESULTS: Both groups did not show significant differences in terms of baseline characteristics, with the exception being the proportion of subphrenic tumours (p=0.031). The RFA and TACE groups did not differ significantly in their 5-year recurrence-free and overall survival rates (17% versus 10.7% and 72.7% versus 51.9%, respectively, with all p-values >0.05). In addition, multivariate analyses revealed that type of treatment was not associated with recurrence-free or overall survival in patients with post-RFA LTP. CONCLUSION: TACE is an effective treatment, comparable to repeated RFA, in patients with LTP after initial RFA when repeated RFA is not feasible.

Radiofrequency ablation versus surgical resection for multiple HCCs meeting the Milan criteria: propensity score analyses of 10-year therapeutic outcomes.

AIM: To assess the long-term therapeutic outcomes of radiofrequency ablation (RFA) versus surgical resection (SR) as a first-line treatment for patients meeting the Milan criteria with multiple hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. Between January 2004 and December 2009, among 3,441 patients with treatment-naive HCCs, 88 patients meeting the Milan criteria with multiple HCCs (Barcelona Clinic Liver Cancer [BCLC] A stage) who underwent either RFA (n=62) or SR (n=26) were included. Recurrence-free survival (RFS) and overall survival (OS) rates were compared by using propensity score matching. In addition, multivariate analysis was performed for assess the prognostic factor. RESULTS: Matching yielded 20 matched pairs of patients. In the two matched groups, the RFS rates were 30% and 30% at 5- and 10-years, respectively, in the RFA group and 60% and 48.6% in the SR group (p=0.054). The corresponding OS rates were 63.3% and 46.1% in the RFA group and 100% and 73.6% in the SR group, respectively (p=0.061). In multivariate analysis, treatment type was independently associated with RFS (hazard ratio [HR]=0.51; p=0.043) whereas it was not a statistically significant factor for OS (HR=0.50; p=0.088). CONCLUSION: In patients meeting the Milan criteria with multiple HCCs (BCLC A stage), SR may provide better RFS compared to RFA.

Prediction and clinical implications of portal vein/superior mesenteric vein invasion in patients with resected pancreatic head cancer: the significance of preoperative CT parameters.

AIM: To determine the preoperative computed tomography (CT) parameters that predict portal vein/superior mesenteric vein (PV-SMV) invasion in patients with pancreatic head cancer, and to assess whether PV-SMV invasion affects patient survival. MATERIALS AND METHODS: Sixty patients with PV-SMV invasion, and 60 randomly selected patients without it, who had undergone preoperative CT and subsequent surgery for pancreatic head cancer were enrolled. The following CT parameters were evaluated using multivariate logistic regression and receiver operating characteristic analyses to predict vessel invasion (tumour size and margin, length of involved vessel, distance from the tumour to the vessel, vessel irregularity, the teardrop sign, and tumour-vein interface [TVI]). The Cox proportional hazard model was used to evaluate the effects of PV-SMV invasion on survival. RESULTS: In multivariate analysis, tumour size (odds ratio [OR]=1.99) and TVI (OR=3.79 [≤90°], 20.66 [>90°, ≤180°], and 47.24 [>180°]) were independent CT predictors of PV-SMV invasion (p<0.05); they achieved a sensitivity of 87%, a specificity of 75%, and an accuracy of 81%; however, PV-SMV invasion did not affect patient survival after surgery (p=0.374). CONCLUSION: In patients with pancreatic head cancer, preoperative CT parameters can predict PV-SMV invasion with high accuracy. PV-SMV invasion did not affect treatment outcome after surgery.

Spin-Orbit Coupling and Interband Transitions in the Optical Conductivity of Sr_{2}RhO_{4}.

The prototypical correlated metal Sr_{2}RhO_{4} was studied using optical and photoemission spectroscopy. At low energies and temperatures, the optical data reveal a complex, multicomponent response that on the surface points to an unconventional metallic state in this material. Via a comparison with photoemission, the anomalous optical response may be attributed to an unexpectedly strong interband transition near 180 meV between spin-orbit coupled bands that are nearly parallel along ΓX. This spin-orbit coupling effect is shown to occur in a number of related metallic ruthenates and explains the previously puzzling optical properties reported for these materials.