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Porous triazine-based macrocycles with 22-carbon and 6-nitrogen ring atoms were efficiently synthesized and used for adsorbing bisphenol A, sulfamethoxazole, sodium dodecyl sulfate, and polyoxyethylene laural ether from aqueous media; after adsorption, simple extraction to desorb the guests from these porous macrocycles demonstrates a facile and efficient approach for porous materials to adsorb and desorb non-volatile organic compounds, thus being potentially applied to other surfactants or antibiotics.

Phthalate esters (PAEs) are emerging hazardous and toxic chemicals that are extensively used as plasticizers or additives. Diethyl phthalate (DEP) and dimethyl phthalate (DMP), two kinds of PAEs, have been listed as the priority pollutants by many countries. PAE hydrolases are the most effective enzymes in PAE degradation, among which family IV esterases are predominate. However, only a few PAE hydrolases have been characterized, and as far as we know, no crystal structure of any PAE hydrolases of the family IV esterases is available to date. HylD1 is a PAE hydrolase of the family IV esterases, which can degrade DMP and DEP. Here, the recombinant HylD1 was characterized. HylD1 maintained a dimer in solution, and functioned under a relatively wide pH range. The crystal structures of HylD1 and its complex with monoethyl phthalate were solved. Residues involved in substrate binding were identified. The catalytic mechanism of HylD1 mediated by the catalytic triad Ser140-Asp231-His261 was further proposed. The hylD1 gene is widely distributed in different environments, suggesting its important role in PAEs degradation. This study provides a better understanding of PAEs hydrolysis, and lays out favorable bases for the rational design of highly-efficient PAEs degradation enzymes for industrial applications in future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal, relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pancreatic cancer is one of the most lethal malignancies worldwide. Acquiring infinite proliferation ability is a key hallmark and basis of tumorigenesis. NOP14 is an identified ribosome biogenesis protein that plays potential roles in cell proliferation. However, the function and molecular mechanism of NOP14 remain ambiguous in most human cancers. In this study, we first investigated the subcellular localization and expression of NOP14 by multiple quantitative assays in pancreatic cancer. We confirmed that NOP14 was mainly localized in nucleolus in human pancreatic cancer cells. Then we studied the regulatory effects of this nucleolus protein on tumor cell proliferation in vitro . NOP14 was demonstrated to play a dominant pro-proliferation role in pancreatic cancer. Furthermore, we identified miR17-5p as a downstream target of NOP14. Transfection of miR17-5p mimics or inhibitors rescued the down- or upregulated effect of NOP14 on cell proliferation by regulating expression of P130. In addition, NOP14 induced expression of transcription factor E2F4 independent of miR17-5p/P130 signaling, which simultaneously activated a set of targeted genes, such as CCNE1, PIM1, AKT1 etc., to promote tumor proliferation. These findings might provide novel insights for better understanding the diverse function of NOP14 in human malignancies to develop new strategies for targeted therapy.

Reasonable yields of two dendrimers with central tetraphenylmethane and peripheral 3 , 5 -di-( tert -butanoylamino)benzoylpiperazine moieties are prepared. These dendrimers have a void space in the solid state so they adsorb guest molecules. Their BET values vary, depending on the H-bond interaction between the peripheral moiety and the gas molecules, and the dendritic framework that fabricates the void space is flexible. In the presence of polar gas molecules such as CO 2 , the BET increases significantly and is about 4-8 times the BET under N 2 . One dendrimer adsorbs cyanobenzene to a level of 436 mg/g, which, to the authors' best knowledge, is almost equivalent to the highest reported value in the literature.

Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB - TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fang, Wu, Sun, Gu, Zhu, Mao, Zhang, Xu, Lu, Tsai, Chen, Lai and Chuang.)

Purpose: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT)., Patients and Methods: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated., Results: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458)., Conclusion: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the early stage of acute ischaemic stroke (AIS). The purpose of this study was to investigate the expression patterns of miRNAs in peripheral blood mononuclear cells (PBMCs) from AIS patients and further explore related molecular mechanisms in stroke-induced immunodeficiency syndrome (SIDS)., Methods: The miRNA expression patterns of PBMCs were detected by miRNA microarray and validated by quantitative real-time polymerase chain reaction (qRT-PCR) in AIS patients and healthy controls. Bioinformatics methods and luciferase reporter assays were used to detect the downstream target genes. Following stimulation with lipopolysaccharide and interleukin-4, the expression of miR-4443, tumor necrosis factor receptor associated factor 4 (TRAF4) and the nuclear factor kappa B (NF-κB) pathway were evaluated. Furthermore, transfection with miR-4443 mimic or inhibitor in the monocytes was carried out to gain insight into the mechanisms in SIDS., Results: Interleukin-10 in AIS patients was significantly higher than that of healthy controls. The miRNA microarray analysis and qRTPCR validation showed that only miR-4443 was upregulated expressed in PBMCs from AIS patients, especially in monocytes. miR-4443 was shown to directly interact with the 3' untranslated regions of TRAF4, resulting in suppression of TRAF4 protein expression. Furthermore, the expression of miR-4443 and TRAF4 was regulated by stimulation with lipopolysaccharide or interleukin-4. Additionally, overexpression of miR-4443 suppressed the TRAF4/Iκα/NF-κB signaling pathway to activate the expression of anti-inflammatory cytokines in monocytes., Conclusions: The increased expression of miR-4443 induced monocyte dysfunction by targeting TRAF4, which may function as a crucial mediator in SIDS., (© 2020 European Academy of Neurology.)

Polydatin is thought to protect mitochondria in different cell types in various diseases. Mitochondrial dysfunction is a major contributing factor in secondary brain injury resulting from traumatic brain injury. To investigate the protective effect of polydatin after traumatic brain injury, a rat brain injury model of lateral fluid percussion was established to mimic traumatic brain injury insults. Rat models were intraperitoneally injected with polydatin (30 mg/kg) or the SIRT1 activator SRT1720 (20 mg/kg, as a positive control to polydatin). At 6 hours post-traumatic brain injury insults, western blot assay was used to detect the expression of SIRT1, endoplasmic reticulum stress related proteins and p38 phosphorylation in cerebral cortex on the injured side. Flow cytometry was used to analyze neuronal mitochondrial superoxide, mitochondrial membrane potential and mitochondrial permeability transition pore opened. Ultrastructural damage in neuronal mitochondria was measured by transmission electron microscopy. Our results showed that after treatment with polydatin, release of reactive oxygen species in neuronal mitochondria was markedly reduced; swelling of mitochondria was alleviated; mitochondrial membrane potential was maintained; mitochondrial permeability transition pore opened. Also endoplasmic reticulum stress related proteins were inhibited, including the activation of p-PERK, spliced XBP-1 and cleaved ATF6. SIRT1 expression and activity were increased; p38 phosphorylation and cleaved caspase-9/3 activation were inhibited. Neurological scores of treated rats were increased and the mortality was reduced compared with the rats only subjected to traumatic brain injury. These results indicated that polydatin protectrd rats from the consequences of traumatic brain injury and exerted a protective effect on neuronal mitochondria. The mechanisms may be linked to increased SIRT1 expression and activity, which inhibits the p38 phosphorylation-mediated mitochondrial apoptotic pathway. This study was approved by the Animal Care and Use Committee of the Southern Medical University, China (approval number: L2016113) on January 1, 2016., Competing Interests: None

Long noncoding RNAs (lncRNAs) have been highlighted to be involved in the pathological process of ischemic stroke (IS). The purpose of the present study was to investigate the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs) of acute IS patients and to explore their utility as biomarkers of IS. Distinctive expression patterns of PBMC lncRNAs were identified by an lncRNA microarray and individual quantitative real-time PCR (qRT-PCR) in four independent sets for 206 IS, 179 healthy controls (HCs), and 55 patients with transient ischemic attack (TIA). A biomarker panel (lncRNA-based combination index) was established using logistic regression. LncRNA microarray analysis showed 70 up-regulated and 128 down-regulated lncRNAs in IS patients. Individual qRT-PCR validation demonstrated that three lncRNAs (linc-DHFRL1-4, SNHG15, and linc-FAM98A-3) were significantly up-regulated in IS patients compared with HCs and TIA patients. Longitudinal analysis of lncRNA expression up to 90 days after IS showed that linc-FAM98A-3 normalized to control levels by day 7, while SNHG15 remained increased, indicating the ability of lncRNAs to monitor IS dynamics. Receiver-operating characteristic (ROC) curve analysis showed that the lncRNA-based combination index outperformed serum brain-derived neurotrophic factor (BDNF) and neurone-specific enolase (NSE) in distinguishing IS patients from TIA patients and HCs with areas under ROC curve of more than 0.84. Furthermore, the combination index increased significantly after treatment and was correlated with neurological deficit severity of IS. The panel of these altered lncRNAs was associated with acute IS and could serve as a novel diagnostic method., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

The triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) is a simple approach to predicting unfavorable outcomes in cardiovascular disease. The influence of TG/HDL-C on acute ischemic stroke remains elusive. The purpose of this study was to investigate the precise effect of TG/HDL-C on 3-month mortality after acute ischemic stroke (AIS). Patients with AIS were enrolled in the present study from 2011 to 2017. A total of 1459 participants from a single city in China were divided into retrospective training and prospective test cohorts. Medical records were collected periodically to determine the incidence of fatal events. All participants were followed for 3 months. Optimal cutoff values were determined using X-tile software to separate the training cohort patients into higher and lower survival groups based on their lipid levels. A survival analysis was conducted using Kaplan-Meier curves and a Cox proportional hazards regression model. A total of 1459 patients with AIS (median age 68.5 years, 58.5% male) were analyzed. Univariate Cox regression analysis confirmed that TG/HDL-C was a significant prognostic factor for 3-month survival. X-tile identified 0.9 as an optimal cutoff for TG/HDL-C. In the univariate analysis, the prognosis of the TG/HDL-C >0.9 group was markedly superior to that of TG/HDL-C ≤0.9 group (P<0.001). A multivariate Cox regression analysis showed that TG/HDL-C was independently correlated with a reduced risk of mortality (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.62; P<0.001). These results were confirmed in the 453 patients in the test cohort. A nomogram was constructed to predict 3-month case-fatality, and the c-indexes of predictive accuracy were 0.684 and 0.670 in the training and test cohorts, respectively (P<0.01). The serum TG/HDL-C ratio may be useful for predicting short-term mortality after AIS., Competing Interests: Competing interests The authors declare that they have no competing interests.

Background: Stroke-induced immunodeficiency syndrome (SIDS) is regarded as a protective mechanism for secondary inflammatory injury as well as a contributor to infection complications. Although stroke-induced hyperactivation of the sympathetic system is proved to facilitate SIDS, the involved endogenous factors and pathways are largely elusive. In this study, we aim to investigate the function of beta-arrestin-2 (ARRB2) in the sympathetic-mediated SIDS., Methods: Splenic ARRB2 expression and the sympathetic system activity were detected after establishing transient models of middle cerebral artery occlusion (MCAO). In addition, a correlation between ARRB2 expression and the sympathetic system activity was analyzed using a linear correlation analysis. Any SIDS reflected in monocyte dysfunction was investigated by measuring inflammatory cytokine secretion and neurological deficit scores and infarct volume were tested to assess neurological outcome. Further, ARRB2 expression in the monocytes was knocked down in vitro by siRNAs. Following the stimulation of noradrenaline and lipopolysaccharide, cytokine secretion and the nuclear factor-κB (NF-κB) pathway were evaluated to gain insight into the mechanisms related to the contribution of ARRB2 to adrenergic-induced monocyte dysfunction., Results: Splenic ARRB2 expression was significantly increased after stroke and also showed a significant positive correlation with the sympathetic system activity. Stroke-induced monocyte dysfunction resulted in an increase of the interleukin-10 (IL-10) level as well as a decrease of the interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels. Also, blockade of adrenergic-activity significantly reversed these cytokine levels, and blockade of adrenergic-activity improved stroke-induced neurological results. However, the improved neurological results had no significant correlation with ARRB2 expression. Furthermore, the in vitro results showed that the deficiency of ARRB2 dramatically repealed adrenergic-induced monocyte dysfunction and the inhibition of NF-κB signaling phosphorylation activity., Conclusions: ARRB2 is implicated in the sympathetic-triggered SIDS, in particular, monocyte dysfunction after stroke. Accordingly, ARRB2 may be a promising therapeutic target for the immunological management of stroke in a clinic.

Although numerous studies have examined the neurotoxicity of acrylamide in adult animals, the effects on neuronal development in the embryonic and lactational periods are largely unknown. Thus, we examined the toxicity of acrylamide on neuronal development in the hippocampus of fetal rats during pregnancy. Sprague-Dawley rats were mated with male rats at a 1:1 ratio. Rats were administered 0, 5, 10 or 20 mg/kg acrylamide intragastrically from embryonic days 6-21. The gait scores were examined in pregnant rats in each group to analyze maternal toxicity. Eight weaning rats from each group were also euthanized on postnatal day 21 for follow-up studies. Nissl staining was used to observe histological change in the hippocampus. Immunohistochemistry was conducted to observe the condition of neurites, including dendrites and axons. Western blot assay was used to measure the expression levels of the specific nerve axon membrane protein, growth associated protein 43, and the presynaptic vesicle membrane specific protein, synaptophysin. The gait scores of gravid rats significantly increased, suggesting that acrylamide induced maternal motor dysfunction. The number of neurons, as well as expression of growth associated protein 43 and synaptophysin, was reduced with increasing acrylamide dose in postnatal day 21 weaning rats. These data suggest that acrylamide exerts dose-dependent toxic effects on the growth and development of hippocampal neurons of weaning rats., Competing Interests: None declared

Uncontrolled hemorrhage and subsequent trauma-induced coagulopathy (TIC) are still the principle causes for preventable death after trauma and early detection and aggressive management have been associated with reduced mortality. Despite increasing knowledge about trauma resuscitation, best practice to treat this newly defined entity is still under debate. A synopsis of best current knowledge with reference to the updated European trauma guideline on the management of severe trauma hemorrhage and TIC is presented. The implementation of evidence-based local protocols and algorithms including clinical quality and safety management systems together with parameters to assess key measures of bleeding control and outcome is advocated., (Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

Traumatic brain injury (TBI) is a major cause of disability and death in patients who experience a traumatic injury. Mitochondrial dysfunction is one of the main factors contributing to secondary injury in TBI-associated brain damage. Evidence of compromised mitochondrial function after TBI has been, but the molecular mechanisms underlying the pathogenesis of TBI are not well understood. Silent information regulator family protein 1 (SIRT1), a member of the NAD + -dependent protein deacetylases, has been shown to exhibit neuroprotective activities in animal models of various pathologies, including ischemic brain injury, subarachnoid hemorrhage and several neurodegenerative diseases. In this study, we investigated whether SIRT1 also exert neuroprotective effect post-TBI, and further explored the possible regulatory mechanisms involved in TBI pathogenesis. A lateral fluid-percussion (LFP) brain injury model was established in rats to mimic the insults of TBI. The expression levels of SIRT1, p-p38, cleaved caspase-9 and cleaved caspase-3 were all markedly increased and reached a maximum at 12 h post-TBI. In addition, mitochondrial function was impaired, evidenced by the presence of swollen and irregularly shaped mitochondria with disrupted and poorly defined cristae, a relative increase of the percentage of neurons with low ΔΨm, the opening of mPTP, and a decrease in neuronal ATP content, especially at 12 h post-TBI. Pretreatment with the SIRT1 inhibitor sirtinol (10 mg/kg, ip) induced p-p38 activation, exacerbated mitochondrial damage, and promoted the activation of the mitochondrial apoptosis pathway. In contrast, pretreatment with the p38 inhibitor SB203580 (200 μg/kg, ip) significantly attenuated post-TBI-induced expression of both cleaved caspase-9 and cleaved caspase-3 and mitochondrial damage, whereas it had no effects on SIRT1 expression. Together, these results reveal that the 12 h after TBI may be a crucial time at which secondary damage occurs; the activation of SIRT1 expression and inhibition of the p38 MAPK pathway may play a neuroprotective role in preventing secondary damage post-TBI. For this reason, both SIRT1 and p38 are likely to be important targets to prevent secondary damage post-TBI.

Background and Purpose: The effect of the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) on clinical outcomes of acute ischaemic stroke (AIS) patients is unclear. This study sought to determine whether the TG/HDL-C ratio in AIS patients is associated with worse outcomes at 3 months., Methods: Acute ischaemic stroke patients who were admitted from 2011 to 2014 were enrolled in this study. TG, total cholesterol (TC), HDL-C and low-density lipoprotein cholesterol (LDL-C) were collected on admission. Three end-points were defined according to the modified Rankin scale (mRS) score at 3 months after symptom onset (excellent outcome, mRS 0-1; good outcome, mRS 0-2; and death, mRS 6)., Results: In all, 1006 patients were included (median age 68.5 years; 58.2% male). Higher TG, non-HDL-C and TG/HDL-C were strongly associated with the three end-points after adjustments: excellent [odds ratio (OR) = 1.39, OR 1.89 and OR 2.34, respectively] and good (OR 1.48, OR 2.90 and OR 4.12) outcomes, and death (OR 0.59, OR 0.29 and OR 0.26). According to receiver operating characteristic (ROC) analysis, the best discriminating factor was a TG/HDL-C ≥ 0.87 for excellent outcomes [area under the ROC curve (AUC) 0.596; sensitivity 73.3%; specificity 42.7%] and non-death (AUC 0.674; sensitivity 67.8%; specificity 60.6%) as well as a TG/HDL-C ≥ 1.01 for a good outcome (AUC 0.652; sensitivity 61.6%; specificity 63.2%). Patients with a TG/HDL-C < 0.87 had a 2.94-fold increased risk of death (95% confidence interval 1.89-4.55) compared with patients with a TG/HDL-C ≥ 0.87., Conclusions: A lower TG/HDL-C was independently associated with death and worse outcome at 3 months in AIS., (© 2016 EAN.)

Purpose: Heat stress stimulation can cause various injuries in human umbilical vein endothelial cells (HUVEC), including apoptotic cell death and an increase in cell permeability. Propofol (PPF), a commonly used anesthetic, is known to have an important role in antioxidation as well as organ protection. Therefore, our aim is to evaluate the protective effects of PPF on heat stress (HS)-induced oxidative stress injury and its possible mechanism of action., Methods: For HS + PPF, cells were treated with propofol followed by 2 h heat stress at 43 °C and then 4 h incubation under normal conditions. For propofol treatment, HUVEC were cultured in serum-free Dulbecco's modified Eagle medium supplemented with 0, 10, 25, or 50 μM propofol for 6 h under normal conditions., Results: During the study, we found that, in HS-induced cellular damage, the protective effect of propofol was related closely with its antioxidation properties. We further revealed that heat stress significantly reduced the level of manganese superoxide demutase (MnSOD) and Cu/Zn SOD, but that propofol could inhibit the reduction of MnSOD only. Transfection of HUVEC with MnSOD small interfering RNA (siRNA) markedly decreased the expression of MnSOD, and the protective effect of propofol in the MnSOD siRNA clones was significantly reduced., Conclusion: Propofol protected the heat stress-injured cells, at least partly, through upregulating MnSOD expression, effectively reducing the direct or indirect cell damage caused by oxidative stress.

Background: Thymic carcinoma is a type of rare and highly malignant tumor that originates from the thymic epithelium. Treatment and prognosis of thymic carcinoma remain controversial. We retrospectively analyzed survival data from a large-sample multicenter database in China., Methods: The Chinese Alliance for Research of Thymoma constructed a retrospective database of patients with thymic epithelial tumors, which enrolled 1930 patients from January 1996 to August 2013, including 329 with thymic carcinomas. In this study, we analyzed clinical, pathologic, and treatment information, measured long-term survival rates, and identified relevant prognostic factors., Results: Of 329 patients, R0 resection was performed in 211 (57.7 %), R1 in 34 (9.2 %), and R2 in 84 (22.5 %).The 3-, 5-, and 10-year survival rates were 78.3, 67.1, and 47.9 %, respectively. In univariate analysis, early Masaoka-Koga stage, R0 resection, and postoperative radiotherapy were associated with better overall survival.Early Masaoka-Koga stage and postoperative radiotherapy were also associated with disease-free survival. In multivariate analyses, R0 resection, Masaoka-Koga stage, and postoperative radiotherapy were significant prognostic factors of survival., Conclusions: Complete resection is the preferred primary treatment for thymic carcinoma. R0 resection, early Masaoka-Koga stage, and postoperative radiotherapy are significant predictors of improved survival.

Based on coupled-mode theory, the mode transition of the high-order cladding modes in a coated long-period tiber grating (LPFG) has been studied firstly; the mode transition region and non-mode transition region of high-order cladding modes are divided. The response characteristic of cladding mode effective index with increasing the overlay thickness is analyzed; the shift of resonant wavelength in the mode transition region will be larger than that in the non-mode transition region. Further, the changes of the resonant wavelength of some high-order cladding modes with grating period are investigated when the cladding radius are different, the shift between two resonant wavelengths of dual peak in the mode transition region is bigger than that in non-mode transition region when the cladding radius are uniform. And the shift between two resonant wavelengths of dual peak will be increased by the decrease of the cladding radius in both mode transition and non-mode transition regions. Finally, the response characteristics of film refractive index of coated LPFG are investigated for a high-order cladding mode while the cladding radius are different and the overlay thickness is located in mode transition region and non-transition mode region, then the optimized design scheme is come up with. The higher sensitivity dual-peak sensor of coated LPFG than the traditional dual-peak sensor will be obtained when the overlay thickness and refractive index is located in the mode transition region and the grating period close to the phase matching turning points. Further, the resolution power of coated LPFG sensor will further be improved by the appropriate reducing of the cladding radius.

In this study, We demonstrated that Bax mitochondrial translocation plays a vital role in the initiation of the mitochondrial signaling pathway upon activation by heat stress. In addition, both p53 mitochondrial translocation and Ca(2+) signal mediated MPTP opening activate Bax mitochondrial translocation. Employing pifithrin-α (a p53 mitochondrial translocation inhibitor) and CsA (a permeability transition pore (MPTP) inhibitor), we found that heat stress induced Bax mitochondrial translocation was significantly inhibited in cells pretreated with both PFT and CsA. Furthermore, we demonstrated that generation of reactive oxygen species (ROS) is a critical mediator in heat stress induced apoptosis and that the antioxidant MnTBAP significantly decreased heat stress induced p53 mitochondrial translocation and Ca(2+) signal mediated MPTP opening, as well as the subsequent Bax mitochondrial translocation and activation of the caspase cascade. Taken together, our results indicate that heat stress induces apoptosis through the mitochondrial pathway with ROS dependent mitochondrial p53 translocation and Ca(2+) dyshomeostasis, and the ensuing intro Bax mitochondrial translocation as the upstream events involved in triggering the apoptotic process observed upon cellular exposure to heat stress.

Background: Emerging evidences indicate that dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer tumorigenesis and progression. LncRNA ANRIL has been shown to promote the progression of gastric cancer. However, the role of lncRNA ANRIL in human non-small cell lung cancer (NSCLC) remains unclear., Methods: Expression of lncRNA ANRIL was analyzed in 87 NSCLC tissues and three lung cancer cell lines by quantitative real-time PCR (qRT-PCR). The correlation of lncRNA ANRIL with clinicopathological features and prognosis was analyzed. Suppression of lncRNA ANRIL using siRNA treatment was performed in order to explore its role in tumor progression., Results: The expression level of lncRNA ANRIL was higher in NSCLC tissues and lung cancer cells than in adjacent non-tumor tissues and normal human bronchial epithelial cells. Higher expression of lncRNA ANRIL in NSCLC tissues was associated with higher TNM stage and advanced lymph node metastasis. Patients with high lncRNA ANRIL expression had poorer overall survival compared with low lncRNA ANRIL group. Univariate and multivariate analyses suggested that high expression of lncRNA ANRIL was an independent poor prognostic indicator for NSCLC patients. Moreover, knockdown of lncRNA ANRIL expression could inhibit lung cancer cell proliferation, migration and invasion in vitro., Conclusions: Our results suggested that lncRNA ANRIL was a potential biomarker for NSCLC prognosis, and the dysregulation of lncRNA ANRIL may play an important role in NSCLC progression., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1707061287149690 .

Purpose: This study was designed to evaluate the feasibility and safety of video-assisted thoracoscopic surgery (VATS), and to compare the surgical results of VATS with the standard median sternotomy (MS) approach., Materials and Methods: Between April 2010 and April 2012, the data of 245 patients who underwent thymectomy for thymic tumors were prospectively collected. Among them, 93 patients with clinical stage I-II disease were retrospectively reviewed., Results: Resection was planned for VATS in 49 cases, and for MS in 44 cases. During operation, there were 3 conversions to open surgery because of local invasion (conversion to thoracotomy in 1 patient, and sternotomy in 2). No transfusion was required in any patient. There was no significant difference in duration or amount of postoperative chest tube drainage between the 2 groups (P>0.05). Operative time, blood loss during operation, average length of the intensive care unit stay, and length of hospital stay were significantly less in the VATS group than the MS group (P<0.05). There were no major perioperative complications or mortality. No recurrence was detected during a median follow-up of 27 months (range, 12 to 36 mo)., Conclusions: VATS thymectomy for early-stage thymic tumors is safe and feasible. In comparison with standard MS, the VATS approach was associated with a shorter intensive care unit stay and hospital stay. Prospective randomized multi-institutional trials with long-term follow-up are needed to compare the oncological outcomes.

Background: Despite increasingly radical surgery for esophageal carcinoma, many patients still develop tumor recurrence after operation. This study was designed to analyze the clinical and pathologic influencing factors of early recurrence in patients with histological node-negative (pN0 stage) esophageal squamous cell carcinoma (ESCC) after radical esophagectomy., Methods: A retrospective study on 112 consecutive pN0 stage ESCC patients who underwent esophagectomy with lymphadenectomy by the same surgical team from January 2004 to December 2010. There were 92 male and 20 female patients, aging from 36 to 80 years with a mean age of 60.3 years. The Cox proportional hazards model was used to determine the independent risk factors for recurrence within 3 years after the operation., Results: Recurrence was recognized in 45 patients (40.2%) within 3 years after operation. The median time to tumor recurrence was 17.4 months. Locoregional recurrence was found in 38 patients (33.9%) and hematogenous metastasis in 7 patients (6.3%). However, locoregional recurrence accounted for 84.4% of all relapse patients. Recurrence closely correlated with tumor location, grade of differentiation, primary tumor stage (pT) and pathologic stage (χ2 = 6.380 to 18.837, p < 0.05). The Cox multivariate analysis showed that upper/middle thoracic location (OR = 1.092, p = 0.049) and pT3-4a stage (OR = 3.296, p = 0.017) were independent risk factors for postoperative locoregional recurrence., Conclusion: Locoregional recurrence was the most common recurrence pattern of patients with pN0 ESCC within 3 years after operation. Upper/middle thoracic location and pT3-4a stage were independent risk factors for locoregional recurrence of pN0 ESCC after radical esophagectomy.

Cells apoptosis induced by intense heat stress is the prominent feature of heat-related illness. However, little is known about the biological effects of heat stress on cells apoptosis. Herein, we presented evidence that intense heat stress could induce early apoptosis of HUVEC cells through activating mitochondrial pathway with changes in mitochondrial membrane potential(ΔΨm), release of cytochrome c, and activation of caspase-9 and -3. We further revealed that p53 played a crucial role in heat stress-induced early apoptosis, with p53 protein rapidly translocated into mitochondria. Using pifithrin-α(PFT), a p53's mitochondrial translocation inhibitor, we found that pretreated with PFT, heat stress induced mitochondrial p53 translocation was significantly suppressed, accompanied by a significant alleviation in the loss of ΔΨm, cytochrome c release and caspase-9 activation. Furthermore, we also found that generation of reactive oxygen species (ROS) was a critical mediator in heat stress-induced apoptosis. In addition, the antioxidant MnTMPyP significantly decreased the heat stress-induced p53's mitochondrial translocation, followed by the loss of ΔΨm, cytochrome c release, caspase-9 activation and heat stress-mediated apoptosis. Conclusively, these findings indicate the contribution of the transcription-independent mitochondrial p53 pathway to early apoptosis in HUVEC cells induced by oxidative stress in response to intense heat stress.

Objective: To discuss the relationship between early coagulability parameters at admission in patients with severe heatstroke and their outcome., Methods: The data from 176 patients with severe heatstroke admitted to Guangzhou General Hospital of Guangzhou Military Command from January 1st, 2002 to August 31st, 2013 were retrospectively analyzed. The patients were divided into survival group (n=150) and non-survival group (n=26) according to the outcome. The incipient values of coagulability function indexes within 24 hours after admission were collected, and prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count (PLT) were compared between two groups to assess the statistically significant indexes for the analysis of the relationship between coagulability parameters and outcome with receiver operator characteristic curve (ROC curve)., Results: Compared with those in survival group, PT and APTT were significantly prolonged in non-survival group [PT: 34.0 (18.8, 45.6) s vs. 18.4 (13.8, 18.0) s, Z=-6.09, P=0.000; APTT: 79.7 (41.0, 91.2) s vs. 60.8 (33.4, 41.0) s, Z=-5.08, P=0.000]. The PLT counts were significantly lower in the non-survival group than those in survival group [ 60.8(4.7, 95.3) × 10⁹/L vs. 128.4(79.8, 180.8) × 10⁹/L, Z=-4.34, P=0.000]. ROC curve analysis showed that the area under ROC curve (AUC) for PT in predicting the death of patients with severe heatstroke was 0.874, with standard error of 0.028 and 95% confidence interval (95%CI) of 0.819-0.927 (P=0.000). The best cut-off was 18.5 s, with sensitivity of 76.9% and specificity of 20.0%. AUC for APTT in predicting the death of patients with severe heatstroke was 0.812, with standard error of 0.047 and 95%CI of 0.740-0.903 (P=0.000). The best cut-off was 46.55 s, with sensitivity of 69.2% and specificity of 14.0%. AUC for PLT in predicting the death of patients with severe heatstroke was 0.767, with standard error of 0.040 and 95%CI of 0.688-0.845 (P=0.000). The best cut-off was 86.5 × 10⁹/L, with sensitivity of 68.0% and specificity of 36.8%., Conclusions: Early prolonged PT and APTT and reduced PLT count are associated with increased risk of death, and it can predict a poor outcome in patients with severe heatstroke.

Objective: To analyze the clinical and pathologic influencing factors of early recurrence in patients with histological node-negative (pN0 stage) esophageal squamous cell carcinoma after radical esophagectomy., Methods: A retrospective study on 112 consecutive pN0 stage esophageal squamous cell carcinoma patients who underwent esophagectomy with lymphadenectomy by the same surgical team from January 2004 to December 2010. There were 92 male and 20 female patients, aging from 36 to 80 years with a mean age of 60.3 years. The Cox proportional hazards model was used to determine the independent risk factors for recurrence within 3 years after the operation., Results: Recurrence was recognized in 45 patients (40.2%) within 3 years after operation. The median time to tumor recurrence was 17.4 months. Locoregional recurrence was found in 38 patients (33.9%), and hematogenous metastasis in 7 patients (6.3%). Recurrence closely correlated with tumor location, grade of differentiation, pT stage and pathologic stage (χ(2) = 6.380 to 18.837, P < 0.05). The Cox multivariate analysis showed that tumor location (RR = 1.092, P = 0.049) and pT3-4a stage (RR = 3.296, P = 0.017) were independent risk factors for postoperative locoregional recurrence., Conclusions: The most common recurrence pattern of patients with pN0 esophageal squamous cell carcinoma would develop recurrence within 3 years after operation is locoregional recurrence. Upper/middle thoracic location and pT3-4a stage are independent risk factors for locoregional recurrence of pN0 esophageal squamous cell carcinoma after operation.

Objective: To analyze the clinical and pathologic risk factors of early recurrence in patients with pathological N1 (pN1) stage esophageal squamous cell carcinoma after radical esophagectomy., Methods: A retrospective study was carried out on 95 consecutive pN1 stage esophageal squamous cell carcinoma patients undergoing esophagectomy with lymphadenectomy by the same surgical team from January 2004 to December 2010 was performed. The Cox proportional hazards model was used to determine the independent risk factors for recurrence and metastasis within 3 years after the operation., Results: Recurrence was identified in 52 patients (54.7%) within 3 years after operation. Local recurrence was found in 42 patients (44.2%), and distant metastasis in 10 patients (10.5%). The Cox multivariate analysis showed that pT3-4a stage (RR=3.604, P=0.027), positive lymph node metastasis in two stations (RR=4.834, P=0.009) or two fields (RR=5.689, P=0.003), and postoperative adjuvant chemotherapy (RR=1.594, P=0.048) were independent risk factors for postoperative recurrence., Conclusions: Postoperative adjuvant chemotherapy can decrease the probability of postoperative recurrence and metastasis of pN1 esophageal squamous cell carcinoma. As for patients who are identified as multi-station or multi-field lymph node metastasis, preoperative induced therapy maybe further improve treatment outcomes.

Objectives: To evaluate the feasibility and safety of video-assisted thoracoscopic surgery (VATS), and to compare surgical results of VATS with standard median sternotomy (MS) and other minimal invasive approaches through various small incisions (SI)., Methods: Totally 111 patients underwent surgery for thymic disorders (maximun diameter ≤ 5 cm, clinical stage I-II for thymic tumors) during March 2010 to June 2012 was retrospectively reviewed. There were 46 male and 65 female patients with a mean age of (51 ± 15) years.Resection via VATS was carried out in 47 patients, via SI in 26 patients, and via MS in 38 patients. Demographic characteristics, operation time, number and cause of conversion, blood loss during operation, duration and amount of chest tube drainage, transfusion, morbidity, and length of hospital stay (LHS) were compared between the three groups., Results: Of the 111 patients, 79 patients had thymic epithelia tumors (stage I 32 patients, stage II 39 patients, stage III 8 patients), 31 patients had benign cysts and 1 patient had tuberculosis.In the VATS group, there were 3 conversions among 38 patients through right-side approach, and 4 conversions among 9 patients through left-side approach. The causes for conversion included dense pleura adhesion, invasion of tumor into adjacent structures (pericardium, lung, or great vessels), and injury of the left inominate vein. There was no significant difference in operative time, blood loss or transfusion during operation, duration or amount of postoperative chest tube drainage among the 3 groups (P > 0.05). Average LHS was significantly shorter in the VATS group (5.7 ± 1.7) days than in the SI group (7.5 ± 2.2) days and the MS group (8.2 ± 1.9) days (F = 3.759, P = 0.002). Total thymectomy was performed in 74 patients, 25 patients (53.2%, 25/47) in VATS group, 11 patients (42.3%, 11/26) in SI group, and 38 patients (100%, 38/38) in MS group. The reset of the patients received tumor resection and partial thymectomy. Among all the subgroups, LHS was the shortest in VATS total thymectomy patients (5.0 ± 1.4) days (F = 5.844, P = 0.001). There was no perioperative mortality. The only major morbidity was a postoperative bleeding necessitating reintervention in SI group., Conclusions: VATS for benign thymic lesions and early-stage thymic tumors is safe and feasible.It is associated with shorter hospital stay compared with other minimal invasive approaches or standard sternotomy.

Squamous cell carcinoma is the major pathology type of esophageal cancer in China, where adenocarcinoma is rare and adenoid cystic carcinoma (ACC) is more rare comparing to the western countries. We report the surgical and pathologic findings of two cases of primary ACC of the esophagus, and review of the Chinese literature of this tumor., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1507582238843246.

Objective: To analyze the differences in perioperative morbidity and lymph node dissection between minimally invasive esophageal carcinoma resection and open procedure., Methods: From January to December 2011, 72 patients with esophageal cancer underwent surgery. Thirty-four patients underwent video-assisted esophagectomy, and 38 underwent open procedure. In the minimally invasive group, there were 7 thoraco-laparoscopic cases, 16 thoracoscopic cases, and 11 laparoscopic cases., Results: The early cases (T1-T2) were more common in the minimally invasive group than that in the open group [79.4%(27/34) vs. 55.3%(21/38), P<0.05]. The complication rate was 41.2%(11/34) in the open group and 42.1%(16/38) in the minimally invasive group, and the difference was not statistically significant (P>0.05). However, the functional complication in minimally invasive group was significantly lower than that in open group [2.9%(1/34) vs. 28.9%(11/38), P<0.01], while technical complications (anastomotic leak and recurrent laryngeal nerve injury) were significantly more common( 38.2% vs. 10.5%, P<0.05). Lymph node group number in minimally invasive group was comparable with the open group (9.1 vs. 11.2, P>0.05), but the number of node in minimally invasive group was significantly lower (13.5±5.9 vs. 17.8±5.2, P<0.05). When stratified by time period, early 17 cases were associated with similar technical complication rate with the late 17 cases (P>0.05), while thoracic lymph node group number, number of node, and positive node were improved in the late phase (all P>0.05)., Conclusions: Minimally invasive esophagectomy reduces functional morbidity, while technical complication including anastomotic leak and recurrent laryngeal nerve injury may be increased. Endoscopic lymph node dissection may be comparable to open surgery.

Objective: To compare the differences in biological behavior and clinical features between adenocarcinoma of the esophagogastric junction (AEG) and lower thoracic esophageal squamous cell cancer (LESC), and to explore reasonable procedures for each cancer., Methods: Clinical data of 111 patients with AEG and 126 patients with LESC who underwent surgery from January 2004 to April 2012 were retrospectively reviewed. Data pertaining to resection rate, lymph node metastasis, and postoperative complication rate were analyzed., Results: The resection rate was 94.6% for AEG and 97.6% for LESC, and the difference was not statistically significant (P<0.05). The rate of lymph node metastasis in the mediastinum in patients with AEG was significantly lower [6.3%(7/111) vs. 32.5%(41/126), P<0.01], while the rate of lymph node metastasis in the abdomen was significantly higher [57.7%(64/111) vs. 34.1%(43/126), P<0.01]. The rate of lymph node metastasis in mediastinum of AEG was 12.5%(4/32) for Siewert I and 4.7%(3/64) for Siewert II, and there was no lymph node metastasis in Siewert III (n=15). For AEG patients who underwent trans-abdominal surgery, the rate of positive lymph node in the middle and lower mediastinum was significantly lower than trans-thoracic surgery [0/22 vs. 7.9% (7/89), P<0.05]. LESC via right thorax with two-field or three-field lymph node dissection was associated with a significantly higher rate of positive lymph node metastasis in the upper mediastinum than that of single incision via left thorax [17.9%(12/67) vs. 0/59, P<0.01]. The postoperative complication rates were 23.4%(26/111) and 27.0%(34/126) respectively, and the difference was not statistically significant(P>0.05)., Conclusions: AEG and LESC show different lymph node metastasis pattern and should be operated differently. Lymphadenectomy in mid-lower mediastinum should be emphasized in Siewert I and Siewert II type cancers.

Background: The prognostic relevance of World Health Organization (WHO) subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thymomas will provide meaningful information for diagnosis and therapeutic management in type B thymoma., Methods: Proteins extracted from twelve type B thymoma tissue specimens (six type B1 and six type B2) were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF-MS. Differentially expressed proteins were then assayed in sixty-nine type B thymoma tissues (including B1, B2 and B3) by tissue array analysis with immunohistochemistry staining. The relationship of their expression with clinicopathological parameters, such as tumor stage or WHO classification, was estimated by Spearman's Rank Correlation Test., Results: Sixteen differentially expressed proteins between type B1 and B2 thymoma tissues were identified. The differential levels of ezrin and glutathione S-transferase pi (GSTP1) were validated using immunohistochemistry staining. A statistically significant difference was observed in the positive rate of ezrin expression between type B1 thymoma and type B3 thymoma (Z = -2.963, P < 0.01). Ezrin showed a tendency to be expressed in higher classification tumors from type B1 to B3. A statistical analysis demonstrated that type B2 and B3 tumors had significantly higher positive expression of GSTP1 than the B1 group (type B2 vs. B1: Z = -2.582, P = 0.01; type B3 vs. B1: Z = -4.012, P ≤ 0.001). The results also showed a strong correlation between GSTP1 and WHO type staging of B1 to B3 tumors (Spearman's correlation coefficient: 0.633, P ≤ 0.001). Statistical analysis showed that there was close correlation between GSTP1 and ezrin expression with the clinical stage (Spearman's correlation coefficients, ezrin: 0.481, P < 0.05; GSTP1: 0.484, P < 0.01)., Conclusions: Differentially expressed proteins between type B1 and B2 thymoma tissues were analyzed by comparative proteomic analysis. The techniques of proteomic analysis and tissue array provide a potential tool for screening of key molecules in type B thymoma histological sub-classifications. The statistical analysis of ezrin and GSTP1 expression by immunohistochemistry, especially GSTP1, may be a useful approach for type B thymoma classification.

Background: As a treatment of depression, the efficacy of conventional repetitive transcranial magnetic stimulation (rTMS) is limited, and symptoms recurrence is easy to occur after the treatment. This study aimed to examine the efficacy and safety of sleep electroencephalogram modulated repetitive rTMS (SEM-rTMS) in the treatment of depression., Methods: After 7 days without psychoactive medication, 164 patients with clinically defined depression were randomly divided into 3 groups: SEM-rTMS group (n = 57), conventional rTMS (C-rTMS, n = 55) group and sham-rTMS group (n = 52). Every patient was treated with the corresponding method for 30 minutes everyday for 10 days. Before and after scores on the 24-item Hamilton rating scale for depression (HAMD-24) and the clinical outcome on the 10th day of therapy for all subjects were analyzed., Results: Twenty-two cases in the SEM-rTMS group obtained improved mood as compared to 6 in the C-rTMS group and 2 in the sham-rTMS group (χ(2) = 15.89, P = 0.0004). After completion of the rTMS phase of the protocol, a (51 ± 5)% reduction of HAMD-24 scores from the baseline in the SEM-rTMS group was found compared with a (34 ± 4)% in the C-rTMS group (q = 26.09, P = 0.001) and a (14 ± 3)% in sham-rTMS group (q = 57.53, P = 0.000). The 88% total effective rate in the SEM-rTMS group was significantly higher than 68% in the C-rTMS group and 20% in the sham-rTMS group (χ(2) = 12.01, P = 0.0025). No significant side effects were noted., Conclusion: SEM-rTMS is an effective and safe way for treating depression with repetitive transcranial magnetic stimulation (ChiCTR-TRC-00000438).

Objective: to evaluate the risk factors for postoperative pulmonary complications following transoral operation for the atlanta-axis disorders., Methods: total 104 cases were collected from January 2005 to June 2009. Twelve variables among patients with PPCs and without PPCs were analyzed by logistic regression analysis., Results: the incidence of postoperative pulmonary complications following transoral operation for the atlanta-axis disorders was 22.1% (23/104). There was significantly difference in 9 variables between patients with PPCs and without PPCs, and 5 variables as serum albumin < 35 g/L (OR = 15.185, P = 0.003), tracheotomy (OR = 32.254, P = 0.015), Frankle grade (OR = 8.866, P = 0.001), the duration of intubation > 4 d (OR = 7.934, P = 0.002), the duration of surgery > 6 h (OR = 16.889, P = 0.006) were found to be significantly related to the development to postoperative pulmonary complications by multivariate analysis., Conclusion: serum albumin < 35 g/L, tracheotomy, Frankle grade, the duration of intubation > 4 d, the duration of surgery > 6 h are the risk factors for postoperative pulmonary complications following transoral operation for the atlanta-axis disorders.

Exposure to microgravity causes a decrease in bone mass and altered bone geometry due to the lack of weight-bearing forces on the skeleton. The mechanical properties of bone are due not only to the structure and geometry, but also to the tissue properties of the bone material itself. To study the effects of microgravity on bone tissue, the mechanical properties of tail suspension rat femurs were investigated. Twelve Sprague-Dawley rats were randomly divided into two groups, tail suspension (TS) and control (CON). On days 0 and 14, the bone mineral density (BMD) of the femurs was determined by Dual Energy X-ray Absorptiometry. After 14 days, three-point bending was used to test the mechanical properties of the whole femur and nanoindentation was used to measure the mechanical properties of the bone materials. The BMD of femurs in TS was significantly lower than that in CON. In the three-point bending testing, the breaking load, stiffness and energy absorption all decreased significantly in the TS group. In the nanoindentation tests, there was no significant difference between TS and CON in elastic modulus (E), while hardness (H) was significantly decreased and E/H significantly increased in TS. Weightlessness affects the intrinsic mechanical properties of bone at the bone material level. It is necessary to investigate further the effect of microgravity on the collagen bone matrix. Nanoindentation is a relatively new technique that is useful for investigating the above changes induced by microgravity and for assessing the efficacy of intervention.

Two-dimensional 1H/13C polarization inversion spin exchange at the magic angle experiments were applied to single crystal samples of amino acids to demonstrate their potential utility on oriented samples of peptides and proteins. High resolution is achieved and structural information obtained on backbone and side chain sites from these spectra. A triple-resonance experiment that correlates the 1H-13Calpha dipolar coupling frequency with the chemical shift frequencies of the alpha-carbon, as well as the directly bonded amide 15N site, is also demonstrated. In this experiment the large 1H-13Calpha heteronuclear dipolar interaction provides an independent frequency dimension that significantly improves the resolution among overlapping 13C resonances of oriented polypeptides, while simultaneously providing measurements of the 13Calpha chemical shift, 1H-13C dipolar coupling, and 15N chemical shift frequencies and angular restraints for backbone structure determination., (Copyright 1999 Academic Press.)