The TOFr of 0.75 to 0.85 is the optimal timing for IONM during thyroid surgery: a prospective observational cohort study.

BACKGROUD: Recurrent laryngeal nerve (RLN) injury is one of the serious complications of thyroid tumour surgery, surgical treatment of thyroid cancer requires careful consideration of the RLN and its impact on glottis function. There has been no unified standard for precise neuromuscular block monitoring to guide the monitoring of RLN in thyroid surgery. This study aimed to investigate the correlation between Train-of-four stabilization ratio (TOFr) and neural signal values of intraoperative neurophysiological monitoring (INOM) during thyroid operation, and further to determine the optimal timing for INOM during thyroid operation. METHODS: Patients scheduled for thyroid tumour resection with INOM and RLN monitoring from April 2018 to July 2018 in our center were recruited. Electromyography (EMG) signals and corresponding TOFr were collected. All nerve stimulation data were included in group VR. Vagus nerve stimulation data were included in Subgroup V. RLN stimulation data were included in Subgroup R. The timing of recording was as follows: Vagus nerve EMG amplitude after opening the lateral space between the thyroid and carotid sheath and before the initiation of thyroid dissection, RLN EMG amplitude at first recognition, RLN EMG amplitude after complete thyroid dissection (Repeat three times), and Vagus nerve EMG amplitude after resection of the thyroid (Repeat three times). Correlation analysis of continuous variables was described by a scatter diagram. Pearson correlation analysis or Spearman correlation analysis was used for the two groups of variables. RESULTS: Finally, 134 vagus nerve signals and 143 RLN signals were analysed after matching with TOFr. The EMG amplitude in the VR group and subgroups after nerve stimulation was positively correlated with TOFr (p < 0.05). In the VR, V and R group, the incidence of EMG ≥ 500 µV in the 0.75 < TOFr ≤ 0.85 interval was significantly higher than the 0 < TOFr ≤ 0.75 interval (P = 0.002, P = 0.013 and P = 0.029), and has no statistical difference compared to 0.85 < TOFr ≤ 0.95 interval (P > 0.05). CONCLUSIONS: The EMG signals of the RLN and vagus nerve stimulation during thyroid surgery were positively correlated with TOFr. TOFr > 0.75 could reflect more than 50% of the effective nerve electrophysiological signals, 0.75 < TOFr ≤ 0.85 interval was the optimal timing for IONM during thyroid surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1800015797) Registered on 20/04/2018. https://www.chictr.org.cn .

Propofol protects against high glucose-mediated endothelial injury via inhibition of COX2 and iNOS expressions.

Perioperative hyperglycemia is a common metabolic disorder in the clinic. Hyperglycemia, via upregulation of E74-like ETS transcription factor 3 (ELF3), induces cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) expressions, thus leading to endothelial apoptosis and vascular endothelial injury. Propofol is a widely used anesthetic. In the present study, we explored whether and how propofol protects against high glucose-induced COX2 and iNOS expressions in human umbilical vein endothelial cells (HUVECs). We found that high glucose level decreases cell viability and increases COX2 and iNOS expressions in HUVECs. Our data also indicated that ELF3 overexpression participates in high glucose-mediated cell viability reduction and high glucose-induced COX2 and iNOS expressions. Moreover, propofol treatment improves high glucose-mediated reduction in cell viability and decreases COX2 and iNOS expressions via inhibition of ELF3 expressions. Furthermore, specificity protein 1 (SP1) was found to regulate ELF3 expression, thus mediating endothelial injury. Propofol inhibits high glucose-induced SP1 expression. High glucose increases the abundance of SP1 bound to the ELF3 promoter, which can be reversed by propofol treatment. The protective effect of propofol is reversed by SP1 overexpression. In conclusion, propofol downregulates high glucose-induced SP1 expression, thus attenuating high glucose-induced ELF3 expression, inhibiting high glucose-induced COX2 and iNOS expressions, and improving high glucose-mediated cell viability reduction in HUVECs.

Sirt7 associates with ELK1 to participate in hyperglycemia memory and diabetic nephropathy via modulation of DAPK3 expression and endothelial inflammation.

Diabetic nephropathy (DN) is one of the most serious complications of advanced diabetes, and increases patient mortality. Recently, epigenetics-mediated hyperglycemic memory in pathological process of DN has received attention. The purpose of this study was to determine the underlying mechanism by which sirt7 modulates hyperglycemic memory in DN. In glomerular endothelial cells (GECs) cultured in high glucose and glomeruli of DN patients and rats, an increase in p65 phosphorylation and endothelial adhesion molecule levels persisted after glucose normalization but was reversed by glucose normalization associated with death-associated protein kinase-3 (DAPK3) knockout or DAPK3 inhibitor. High glucose-mediated decrease in sirt7, the deacetylase modulating H3K18-acetylation (H3K18ac), was sustained after normoglycemia. Sirt7 overexpression accompanied by glucose normalization suppressed DAPK3 expression and inflammation in GECs. Moreover, sh-sirt7-induced inflammation was inhibited by si-DAPK3. Furthermore, sirt7 and H3K18ac were located at the DAPK3 promoter region. ELK1 was found to combine with sirt7. si-ELK1 supplemented with normoglycemia inhibited high glucose-induced DAPK3 expression and inflammation in GECs. ELK1 overexpression-mediated inflammation was inhibited by si-DAPK3. In addition, ELK1 and sirt7 were located at the same promoter region of DAPK3. ELK1 overexpression enhanced DAPK3 promoter activity, which disappeared after specific binding site mutation. In vivo, sirt7 overexpression decreased inflammation and improved renal function during insulin treatment of DN rats, whereas insulin alone did not work. Our data demonstrated high glucose-mediated mutual inhibition between sirt7 and ELK1 induced DAPK3 transcription and inflammation despite normoglycemia in GECs, thus forming a vicious cycle and participating in the occurrence of hyperglycemic memory in DN.

SETD8 cooperates with MZF1 to participate in hyperglycemia-induced endothelial inflammation via elevation of WNT5A levels in diabetic nephropathy.

OBJECTIVE: Diabetic nephropathy (DN) is regarded as the main vascular complication of diabetes mellitus, directly affecting the outcome of diabetic patients. Inflammatory factors were reported to participate in the progress of DN. Wingless-type family member 5 (WNT5A), myeloid zinc finger 1 (MZF1), and lysine methyltransferase 8 (SETD8) have also been reported to elevate inflammatory factor levels and activate the nuclear factor kappa B (NF-κB) pathway to induce endothelial dysfunction. In the current study, it was assumed that MZF1 associates with SETD8 to regulate WNT5A transcription, thus resulting in hyperglycemia-induced glomerular endothelial inflammation in DN. METHODS: The present study recruited 25 diagnosed DN patients (type 2 diabetes) and 25 control participants (nondiabetic renal cancer patients with normal renal function, stage I-II) consecutively. Moreover, a DN rat and cellular model was constructed in the present study. Immunohistochemistry, Western blot, and quantitative polymerase chain reaction (qPCR) were implemented to determine protein and messenger RNA (mRNA) levels. Coimmunoprecipitation (CoIP) and immunofluorescence were implemented in human glomerular endothelial cells (HGECs). Chromatin immunoprecipitation assays and dual luciferase assays were implemented to determine transcriptional activity. RESULTS: The results of this study indicated that levels of WNT5A expression, p65 phosphorylation (p-p65), and inflammatory factors were all elevated in DN patients and rats. In vitro, levels of p-p65 and inflammatory factors increased along with the increase of WNT5A expression in hyperglycemic HGECs. Moreover, high glucose increased MZF1 expression and decreased SETD8 expression. MZF1 and SETD8 inhibit each other under the stimulus of high glucose, but cooperate to regulate WNT5A expression, thus influencing p-p65 and endothelial inflammatory factors levels. Overexpression of MZF1 and silencing of SETD8 induced endothelial p-p65 and inflammatory factors levels, which can be reversed by si-WNT5A. Mechanistic research indicated that MZF1, SETD8, and its downstream target histone H4 lysine 20 methylation (H4K20me1) all occupied the WNT5A promoter region. sh-SETD8 expanded the enrichment of MZF1 on WNT5A promoter. Our in vivo study proved that SETD8 overexpression inhibited levels of WNT5A, p-p65 expression, and inflammatory factors in DN rats. CONCLUSIONS: MZF1 links with SETD8 to regulate WNT5A expression in HGECs, thus elevating levels of hyperglycemia-mediated inflammatory factors in glomerular endothelium of DN patients and rats. Trial registration ChiCTR, ChiCTR2000029425. 2020/1/31, http://www.chictr.org.cn/showproj.aspx?proj=48548.

The SETD8/ELK1/bach1 complex regulates hyperglycaemia-mediated EndMT in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN), the most common microvascular complication in patients with diabetes, induces kidney failure. Previous research showed that endothelial-to-mesenchymal transition (EndMT) of human glomerular endothelial cells (HGECs) is involved in the progression of DN. Moreover, SET domain-containing protein 8 (SETD8), ETS-domain containing protein (ELK1) and BTB and CNC homology 1 (bach1) all participate in endothelial injury. In this study, we hypothesize that the SETD8/ELK1/bach1 functional axis is involved in mediating EndMT in diabetic nephropathy. METHODS: Immunohistochemistry, Western blotting and qPCR were performed to determine the protein and mRNA levels of genes in HGECs and the kidney tissues of participants and rats. Immunofluorescence, Co-IP and GST pulldown assays were performed to verify the direct interaction between SETD8 and ELK1. ChIP and dual-luciferase assays were performed to determine the transcriptional regulation of bach1 and Snail. AVV-SETD8 injection in rat kidney was used to verify the potential protective effect of SETD8 on DN. RESULTS: Our current study showed that hyperglycaemia triggered EndMT by increasing Snail expression both in vitro and in vivo. Moreover, high glucose increased bach1 expression in HGECs, positively regulating Snail and EndMT. As a transcription factor, ELK1 was augmented and participated in hyperglycaemia-induced EndMT via modulation of bach1 expression. Moreover, ELK1 was found to associate with SETD8. Furthermore, SETD8 negatively regulated EndMT by cooperating with bach1 to regulate Snail transcription. Furthermore, histone H4-Lys-20 monomethylation (H4K20me1), which is downstream of SETD8, was accompanied by ELK1 localization at the same promoter region of bach1. ELK1 overexpression enhanced bach1 promoter activity, which disappeared after specific binding site deletion. Mutual inhibition between ELK1 and SETD8 was found in HGECs. In vivo, SETD8 overexpression decreased ELK1 and bach1 expression, as well as EndMT. Moreover, SETD8 overexpression improved the renal function of rats with DN. CONCLUSIONS: SETD8 cooperates with ELK1 to regulate bach1 transcription, thus participating in the progression of DN. In addition, SETD8 interacts with bach1 to modulate Snail transcription, thus inducing EndMT in DN. SETD8 plays a core role in the SETD8/ELK1/bach1 functional axis, which participates in hyperglycaemia-mediated EndMT in DN, and SETD8 may be a potential therapeutic target for DN. Trial registration ChiCTR, ChiCTR2000029425. 2020/1/31, http://www.chictr.org.cn/showproj.aspx?proj=48548.

Epigenetics in the pathogenesis of diabetic nephropathy.

Diabetic nephropathy (DN), which is a common microvascular complication with a high incidence in diabetic patients, greatly increases the mortality of patients. With further study on DN, it is found that epigenetics plays a crucial role in the pathophysiological process of DN. Epigenetics has an important impact on the development of DN through a variety of mechanisms, and promotes the generation and maintenance of metabolic memory, thus ultimately leading to a poor prognosis. In this review we discuss the methylation of DNA, modification of histone, and regulation of non-coding RNA involved in the progress of cell dysfunction, inflammation and fibrosis in the kidney, which ultimately lead to the deterioration of DN.

Horner Syndrome Following Intercostal Nerve Block Via an Anterolateral Approach in Breast Lumpectomy: A Prospective Nested Case-control Study.

BACKGROUND: Lumpectomy is important for preventing malignant changes in benign tumors and diagnosing malignant tumors. Intercostal nerve blocks (ICNBs) are useful for breast lumpectomy as either the primary anesthetic or as an adjuvant anesthetic procedure. To our knowledge, no studies have evaluated the association between Horner syndrome and ICNB. OBJECTIVES: This study aimed to explore the characteristics of and related risk factors for Horner syndrome after ICNB. STUDY DESIGN: A prospective, nested case-control study. SETTING: Fudan University Shanghai Cancer Centre from April 2020 through July 2020. METHODS: Patients scheduled for breast lumpectomy under ICNB from April 2020 through July 2020 in our hospital were recruited. The ICNB was introduced at the intersection of the midaxillary line and the inferior border of the ribs, according to the location of the mass. Horner syndrome indicators were assessed one, 5, 10, 15, 30, 45, and 60 minutes and 3, 6, 12 and 24 hours after ICNB. Personal data (age, body mass index [BMI], ASA classes), data on anesthetic (the puncture points, dose of local anesthetics, duration of ICNB, Horner syndrome indicators, other complications) and data on postoperative recovery (postoperative activity time, postoperative feeding time) were recorded. Univariate and multivariate logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. RESULTS: Ipsilateral Horner syndrome was found in 35 of 998 (3.5%) patients. Ipsilateral miosis, the first symptom to appear and last to disappear, occurred within 4 minutes and lasted 45 minutes to 240 minutes after ICNB. Seven patients showed obvious ipsilateral facial flushing. Logistic multivariate regression analysis showed that independent risk factors for Horner syndrome after ICNB were age <= 45 years, body mass index <= 18.5 kg/m2, and the need for a second ICNB. LIMITATIONS: Firstly, the patients in this study are all adult women, and the applicability of other populations is uncertain. Secondly, the flow trajectory of local anesthetics was not confirmed by imaging tracers. CONCLUSIONS: ICNB via an anterolateral approach promoted enhanced recovery after breast lumpectomy. The incidence of Horner syndrome following ICNB for breast lumpectomy was 3.5%. Horner syndrome occurred on the ipsilateral side of the ICNB and was reversible. Younger age, lower BMI, and the need for a second ICNB were risk factors for Horner syndrome after ICNB. KEY WORDS: Horner's syndrome, intercostal nerve block, breast lumpectomy, enhanced recovery.

c-Myc participates in high glucose-mediated endothelial inflammation via upregulation of IRAK1 expression in diabetic nephropathy.

Diabetic nephropathy (DN) is a common vascular complication of diabetes. Endothelial adhesion molecules are involved in physiopathology of DN. Interleukin-1 receptor-associated kinase 1 (IRAK1) and c-Myc participate in inflammation in DN. We hypothesized c-Myc modulates IRAK1 expression, contributing to hyperglycemia-mediated endothelial inflammation. The expression of endothelial adhesion molecules and IRAK1 were increased in glomerular endothelium of DN patients and rats. Our cellular experiments indicated high glucose-induced endothelial cell inflammation was inhibited by si-IRAK1. Additionally, high glucose increased c-Myc expression. si-c-Myc inhibited high glucose-mediated increase of IRAK1 levels and endothelial cell inflammation. c-Myc overexpression-mediated endothelial cell inflammation was counteracted by si-IRAK1. c-Myc also interacted with lysine methyltransferase 5A (KMT5A). Furthermore, high glucose decreased KMT5A expression and histone H4 lysine 20 methylation (H4K20me1). KMT5A upregulation decreased high glucose-mediated increase of IRAK1 levels as well as endothelial inflammation. KMT5A silencing-mediated endothelial inflammation was reversed by si-IRAK1. Mechanistic research indicated that c-Myc and H4K20me1 occupied IRAK1 promoter region. KMT5A silencing augmented the active action of c-Myc on IRAK1 levels. Our in vivo experiments represented KMT5A is downregulated and c-Myc is upregulated in DN patients and rats. KMT5A interacts with c-Myc to modulate IRAK1 expression, thus contributing to hyperglycemia-mediated endothelial inflammation in DN.

The CREB/KMT5A complex regulates PTP1B to modulate high glucose-induced endothelial inflammatory factor levels in diabetic nephropathy.

Diabetic nephropathy (DN) is the primary microvascular complication of diabetes mellitus and may result in end-stage renal disease. The overproduction of various inflammatory factors is involved in the pathogenesis of DN. Protein tyrosine phosphatase 1B (PTP1B) modulates the expression of a series of cytokines and nuclear factor kappa B (NF-κB) activity. cAMP response element-binding protein (CREB) and lysine methyltransferase 5A (KMT5A) have been reported to participate in the maintenance of a healthy endothelium. In the present study, we hypothesise that CREB associates with KMT5A to modulate PTP1B expression, thus contributing to high glucose-mediated glomerular endothelial inflammation. Our analyses revealed that plasma inflammatory factor levels, glomerular endothelial p65 phosphorylation and PTP1B expression were increased in DN patients and rats. In vitro, high glucose increased endothelial inflammatory factor levels and p65 phosphorylation by augmenting PTP1B expression in human umbilical vein endothelial cells (HUVECs). Moreover, high glucose decreased CREB and KMT5A expression. CREB overexpression and KMT5A overexpression both inhibited high glucose-induced PTP1B expression, p65 phosphorylation and endothelial inflammatory factor levels. si-CREB- and sh-KMT5A-induced p65 phosphorylation and endothelial inflammatory factor levels were reversed by si-PTP1B. Furthermore, CREB was associated with KMT5A. Mechanistic research indicated that CREB and histone H4 lysine 20 methylation (H4K20me1, a downstream target of KMT5A) occupy the PTP1B promoter region. sh-KMT5A augmented PTP1B promoter activity and activated the positive effect of si-CREB on PTP1B promoter activity. Our in vivo study demonstrated that CREB and KMT5A were downregulated in glomerular endothelial cells of DN patients and rats. In conclusion, CREB associates with KMT5A to promote PTP1B expression in vascular endothelial cells, thus contributing to hyperglycemia-induced inflammatory factor levels in DN patients and rats.

Paradoxical carbon dioxide embolism during laparoscopic surgery without intracardiac right-to-left shunt: two case reports and a brief review of the literature.

We herein report two cases of paradoxical carbon dioxide (CO2) embolism during laparoscopic nephrectomy and hepatic left lateral lobectomy without evidence of a right-to-left shunt or obvious rupture of blood vessels. Transesophageal echocardiography detected paradoxical CO2 embolism before the end-tidal CO2 partial pressure (PETCO2) dropped from baseline. The pneumoperitoneum was reduced or stopped immediately after detection of the embolism. One patient developed a postoperative epileptiform seizure. In the other patient, many gas bubbles were drawn out from the central venous line. We speculate that rapid introduction of pneumoperitoneum pushed a large amount of CO2 into the abdominal blood vessels, exceeding the gas exchange capacity of the lung and causing CO2 bubble formation in the left-side cardiac system. These two cases indicate that intraoperative transesophageal echocardiography can reduce the influence of CO2 embolism during laparoscopic tumor surgery by early diagnosis of the embolism and provide helpful information to establish a list of differential diagnoses of postoperative complications.

ACAT2 Promotes Cell Proliferation and Associates with Malignant Progression in Colorectal Cancer.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a major disease that threatens human health. It has been reported that the acyl-coenzyme A (CoA): cholesterol acyltransferase 2 (ACAT2) gene can promote the progression of hepatocellular carcinoma, but its function in CRC is still unclear. In this study, we aimed to elucidate the function of ACAT2 in CRC. METHODS: Western blot and qPCR were used to detect the relative level of ACAT2 in CRC tissue and adjacent non-cancerous tissues, and then the association between ACAT2 expression and the clinicopathological features and survival of CRC patients were assessed. The expression of ACAT2 in CT26 and DLD1 cells was down-regulated by siRNA, and the effects of ACAT2 knockdown on cell proliferation were examined. The inhibitory effects of ACAT2 knockdown were further confirmed by tumor growth assays in vivo. RESULTS: Our data showed that the expression of ACAT2 in CRC tissues was markedly higher than in adjacent non-cancerous tissues. The high expression of ACAT2 was significantly associated with tumor size, lymph node metastasis and clinical stage. The increased expression of ACAT2 was also significantly associated with worse 5-year overall survival of CRC patients. siRNA-mediated ACAT2 knockdown strongly inhibited CT26 and DLD1 cells proliferation and induced G0/G1 phase cell cycle arrest and apoptosis in these cells. Knockdown of ACAT2 expression suppressed the growth of CRC and inhibited the expression of Ki67 in vivo. CONCLUSION: Our study demonstrated that ACAT2 played a positive role in regulating the proliferation of CRC and may be useful as a potential biomarker and therapeutic target for this disease.

Effects of MFHAS1 on cognitive impairment and dendritic pathology in the hippocampus of septic rats.

AIMS: To investigate the effects of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) on cognitive dysfunction, the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and amyloid ß peptide (Aß) in the hippocampus, as well as dendritic pathology in the hippocampal CA1 region in sepsis-associated encephalopathy (SAE) rats. MAIN METHODS: The rats were randomly divided into four groups: 1) control group (subjected to sham surgery), 2) control plus Mfhas1 siRNA group (rats received intracerebroventricular injection of Mfhas1 siRNA after sham surgery), 3) CLP plus control siRNA group (rats received intracerebroventricular injection of control siRNA after cecal ligation and puncture (CLP)), 4) CLP plus Mfhas1 siRNA group (rats received intracerebroventricular injection of Mfhas1 siRNA after CLP). The learning and memory capabilities of the rats were examined by means of fear conditioning and Barnes maze test. The concentration of TNF-α and IL-1ß was determined by enzyme-linked immunosorbent assay. The efficiency of siRNA transfection, MFHAS1 and Aß expression were detected by Western blotting. Total branch lengths of pyramidal dendrites of the CA1 basilar trees and spine density were determined by Golgi staining. KEY FINDINGS: We observed that MFHAS1 knock-down by Mfhas1 siRNA intracerebroventricular injection could improve cognitive impairment, reduce the expression of TNF-α, IL-1ß and Aß in the hippocampus induced by CLP, and alleviate the dendritic spinal loss of the pyramidal neurons, as well as increase the dendritic branching of the CA1 basilar trees of septic rats. SIGNIFICANCE: MFHAS1 knock-down can alleviate cognitive impairment, neuroinflammation and dendritic spinal loss in SAE rats.

Oriented epitaxial TiO2 nanowires for water splitting.

Highly oriented epitaxial rutile titanium dioxide (TiO2) nanowire arrays have been hydrothermally grown on polycrystalline TiO2 templates with their orientation dependent on the underlying TiO2 grain. Both the diameter and areal density of the nanowires were tuned by controlling the precursor concentration, and the template surface energy and roughness. Nanowire tip sharpness was influenced by precursor solubility and diffusivity. A new secondary ion mass spectrometer technique has been developed to install additional nucleation sites in single crystal TiO2 templates and the effect on nanowire growth was probed. Using the acquired TiO2 nanowire synthesis knowhow, an assortment of nanowire arrays were installed upon the surface of undoped TiO2 photo-electrodes and assessed for their photo-electrochemical water splitting performance. The key result obtained was that the presence of short and dispersed nanowire arrays significantly improved the photocurrent when the illumination intensity was increased from 100 to 200 mW cm-2. This is attributed to the alignment of the homoepitaxially grown nanowires to the [001] direction, which provides the fastest charge transport in TiO2 and an improved pathway for photo-holes to find water molecules and undertake oxidation. This result lays a foundation for achieving efficient water splitting under conditions of concentrated solar illumination.

The effect of neuraxial anesthesia on cancer recurrence and survival after cancer surgery: an updated meta-analysis.

Several animal and observational studies have evaluated the effects of neuraxial anesthesia on the recurrence and survival of cancer surgery; studies reported benefit, whereas others did not. To provide further evidence that neuraxial anesthesia(combined with or without general anesthesia (GA))may be associated with reduced cancer recurrence and long-term survival after cancer surgery, we conducted this meta-analysis. A total of 21 studies were identified and analyzed, based on searches conducted using PubMed, Web of Science, EMBASE database and the Cochrane Database of Systematic Reviews. After data abstraction, adjusted hazard ratios (HR) with 95% confidence intervals (CIs) were used to assess the impact of neuraxial anesthesia (combined with or without GA) and GA on oncological outcomes after cancer surgery. For overall survival (OS), a potential association between neuraxial anesthesia and improved OS (HR 0.853, CI 0.741-0.981, P = 0.026, the random-effects model) was observed compared with GA. Specifically, we found a positive association between neuraxial anesthesia and improved OS in colorectal cancer (HR 0.653, CI 0.430-0.991, P = 0.045, the random-effects model). For recurrence-free survival (RFS), a significant association between neuraxial anesthesia and improved RFS (HR 0.846, CI 0.718-0.998, P = 0.047, the random-effects model) was detected compared with GA. Our meta-analysis suggests that neuraxial anesthesia may be associated with improved OS in patients with cancer surgery, especially for those patients with colorectal cancer. It also supports a potential association between neuraxial anesthesia and a reduced risk of cancer recurrence. More prospective studies are needed to elucidate whether the association between neuraxial use and survival is causative.

Simian Immunodeficiency Virus Impacts MicroRNA-16 Mediated Post-Transcriptional Regulation of mu Opioid Receptor in CEM ×174 Cells.

Although the mechanism which regulates transcription in the 5'-UTR of the mu opioid receptor gene (OPRM1) in lymphocytes has been well-studied, a question remains as to whether there is post-transcriptional regulation of OPRM1 gene in lymphocytes. In this study, the authors describe both the role played by miRNAs and the impact of SIVmac239 infection on post-transcriptional regulation of OPRM1 gene in CEM ×174 cells. Our results show that miR-16 is able to bind the target site in the range of 8699-8719 nt from the stop codon in MOR-1 mRNA 3'-UTR and suppress the expression of OPRM1 gene. Mutation of this target site reduces the effect of miR-16. Morphine (1 µM) inhibits the expression of miR-16, and this effect is reversed by the antagonist naloxone. Thus, morphine may up-regulate receptor level by both stimulating OPRM1 gene transcription and stabilizing its mRNA. SIVmac239 infection results in an apparent elevation of miR-16 and gradual reduction of OPRM1 gene expression. The inverse correlation of elevated miR-16 and reduced OPRM1 gene expression under viral loading confirmed the effect of SIVmac239 on post-transcriptional regulation of OPRM1 gene in lymphocytes. The authors conclude that miR-16 is a primary factor in post-transcriptional regulation of OPRM1 gene. SIVmac239 upregulates miR-16 levels and consequently suppresses OPRM1 gene expression. This finding will be helpful for full understanding of the regulatory mechanism of OPRM1 gene in lymphocytes, as well as the synergistic mechanism of HIV infection and morphine addiction in the pathogenesis of AIDS.

Alpha fetoprotein mediates HBx induced carcinogenesis in the hepatocyte cytoplasm.

Although tumor-associated fetal protein AFP has demonstrated utility as a clinical tumor marker, the significance of intracellular AFP is still unclear. The aim of this study was to explore the role of cytoplasmic AFP during HBx induced carcinogenesis, which had not previously been recognized; 614 HCC patients were analyzed for correlation of HBV infection with AFP level, and much higher AFP levels were found in HBsAg positive patients. Tumor tissue specimens from 20 HCC patients were used for analysis of AFP and GADD45α. Analysis of HCC specimens showed that upregulation of cytoplasmic AFP is associated with down-regulation of GADD45α in neoplastic tissue. Transfected HBx promotes transcription of AFP by acting on the elements in the AFP gene regulatory region. HBx itself did not directly impact transcription of GADD45α. However, the obstruction of RAR signaling by HBx induced elevation of AFP, which led to down-regulation of GADD45α. Cytoplasmic AFP was able to interact with RAR, disrupting its entrance into the nucleus and binding to the elements in the regulatory region of the GADD45α gene. Knockdown of AFP in siRNA-transfected AFP positive cell lines was synchronously associated with an incremental increase of RAR binding to DNA, as well as upregulation of GADD45α and it was contrary in AFP gene-transfected AFP negative cell lines. These results indicate cytoplasmic AFP is not only a histochemical tumor biomarker for human hepatoma but is also an intracellular signal molecule and potential participant in HBx induced hepatocarcinogenesis.

Evaluation of metal/indium-tin-oxide for transparent low-resistance contacts to p-type GaN.

In search of a better transparent contact to p-GaN, we analyze various metal/indium-tin-oxide (ITO) (Ag/ITO, AgCu/ITO, Ni/ITO, and NiZn/ITO) contact schemes and compare to Ni/Au, NiZn/Ag, and ITO. The metal layer boosts conductivity while the ITO thickness can be adjusted to constructive transmission interference on GaN that exceeds extraction from bare GaN. We find a best compromise for an Ag/ITO (3 nm/67 nm) ohmic contact with a relative transmittance of 97% of the bare GaN near 530 nm and a specific contact resistance of 0.03 Ω·cm2. The contact proves suitable for green light-emitting diodes in epi-up geometry.

Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma.

BACKGROUND & AIMS: The function of cytoplasmic AFP as a regulatory factor in the growth of tumor cells has been well defined. However, its precise mechanism of action and its clinical significance remain to be worked out. METHODS: Specimens from HCC patients were analyzed by using immunohistochemistry, co-immunoprecipitation (CoIP), and chromatin immunoprecipitation (ChIP) assays to evaluate the role of AFP in RAR signaling-mediated carcinogenesis. Quantitative real-time reverse transcription PCR, Western blotting, confocal microscopy, CoIP, GST pull-down, siRNA, gene transfection, and ChIP assays were also used for analysis of cell lines. RESULTS: RAR is able to interact with cytoplasmic AFP and binds to the element of the regulatory region of the Fn14 gene in the neoplastic tissue of HCC patients. An assay of hepatocyte cell lines of differing AFP expression showed that cytoplasmic AFP is able to block ATRA-induced nuclear translocation of RAR and expression of the Fn14 gene. Knockdown of AFP in siRNA-transfected HepG2 and Bel7402 cells led to greater binding of RAR to its response element. The expression of the Fn14 gene was therefore up regulated as reflected by increases in mRNA and protein levels. Conversely, transfection of HLE and L02 cells (AFP negative) with the afp gene resulted in apparent reduction of RAR binding to DNA and Fn14 protein. CONCLUSIONS: Demonstration of the involvement of cytoplasmic AFP in RAR-mediated expression of the Fn14 gene strongly indicates AFP plays a signal molecule-like role in the regulation of hepatocellular carcinoma growth.