Percutaneous fluoroscopically-guided transcervical retrograde access facilitates successful thoracic duct embolization after failed antegrade transabdominal access.

The purpose of this study was to demonstrate the feasibility of percutaneous fluoroscopically-guided transcervical retrograde access into the thoracic duct following unsuccessful transabdominal cisterna chyli cannulation to perform thoracic duct embolization for the treatment of chylothorax. Five patients, including three (60%) women and two (40%) men, with median age of 62 years, underwent percutaneous transcervical thoracic duct access and embolization after failed transabdominal cisterna chyli cannulation for the treatment of chylothorax. In all patients, fluoroscopically-guided percutaneous transcervical retrograde access into the distal thoracic duct was achieved using a 21-gauge needle and an 0.018-inch wire. Following advancement of a microcatheter, retrograde lymphangiography was performed to identify the location of thoracic duct injury. A combination of 2:1 ethiodized oil to cyanoacrylate mixtures, platinum microcoils, or stent-grafts were used to treat the chylous leaks. Technical successes, procedure durations, fluoroscopy times, blood losses, immediate adverse events, clinical successes, and follow-up durations were recorded. Technical success was defined as cannulation of the distal thoracic duct using a transcervical approach followed by treatment of the thoracic duct injury. Adverse events were classified according to the Society of Interventional Radiology guidelines. Clinical success was defined as resolution of the presenting chylothorax. Percutaneous transcervical retrograde thoracic duct access and treatment was technically successful in all patients (n=5). Median procedure duration was 173 minutes (range: 136-347 minutes) with a median fluoroscopy time of 94.7 minutes (range: 47-125 minutes). Median blood loss was 10 mL (range: 5-20 mL). No minor or major adverse occurred. Clinical success was achieved in all patients (n=5). Median follow-up was 372 days (range: 67-661 days). Percutaneous fluoroscopically- guided transcervical retrograde thoracic duct access is an effective and safe method to perform thoracic duct embolization following unsuccessful transabdominal cisterna chyli cannulation for the treatment of chylothorax.

Gastric infusion of short-chain fatty acids can improve intestinal barrier function in weaned piglets.

BACKGROUND: The present study was conducted to investigate the effects of gastric infusion of short-chain fatty acids (SCFA) on gut barrier function in a pig model. In this study, 21 DLY barrows with an average initial body weight of (8.31 ± 0.72) kg were randomly allotted into three treatments: (1) control, (2) infusing low SCFA, S1, (3) infusing high SCFA, S2. The experimental period lasted for 7 days. RESULTS: Gastric infusion of SCFA increased the concentrations of SCFA in serum and digesta, and enhanced the mRNA and protein abundances of SCFA receptors in pig intestine (P < 0.05). Moreover, gastric infusion of SCFA led to alteration of intestinal morphology, elevation of intestinal development-related gene abundances, and decrease of apoptotic cell percentage, as well as reduction of pro-apoptosis gene and protein abundances (P < 0.05). Besides, the jejunal SLC7A1 and ileal DMT1 mRNA abundances in the SCFA infusion groups were higher than those in the control group (P < 0.05). Additionally, gastric infusion of SCFA increased the mRNA abundances of Occludin and Claudin-1 in the duodenum and ileum, enhanced Lactobacillus spp counts in the ileal digesta, decreased the mRNA and protein abundances of IL-1ß in the colon, and reduced Escherichia coli count in the ileal digesta (P < 0.05). CONCLUSIONS: These data indicated that gastric infusion of SCFA, especially high SCFA concentration, may be beneficial to gut development of piglets via improving gut morphology, decreasing apoptotic cell percentage, and maintaining intestinal barrier function.

Research on changes in cognitive function, ß-amyloid peptide and neurotrophic factor in stroke patients.

OBJECTIVE: To investigate the changes as well as the related mechanism in cognitive function and levels of serum ß-amyloid peptide (Aß) and brain-derived neurotrophic factor (BDNF) in stroke patients. PATIENTS AND METHODS: A total of 30 patients with acute stroke treated in our hospital from June 2015 to September 2016 were selected as stroke group, while 30 volunteers during the same period were enrolled as control group. Changes in cognitive function of patients were evaluated using the Montreal Cognitive Assessment (MoCA) and mini-mental state examination (MMSE) before and after the treatment. At the same time, the concentrations of serum Aß1-40 and BDNF were detected, and their correlations with the MMSE score were analyzed. Finally, levels of serum cyclic adenosine monophosphate (cAMP) and phosphorylated-cAMP-response element binding protein (p-CREB), and the phosphorylation level of Tau protein were detected by Western blotting. RESULTS: MoCA and MMSE scores of patients in stroke group were significantly lower than those in control group (p < 0.01), and the scores were significantly higher in stroke patients after treatment than those before treatment (p < 0.01). Compared with those in control group, the serum Aß1-40 concentration in patients in stroke group was significantly increased (p < 0.01), but the BDNF level was significantly decreased (p < 0.01). Compared with those before treatment, the serum Aß1-40 concentration in patients was significantly decreased after treatment (p < 0.01), but the BDNF concentration was significantly increased (p < 0.01). Correlation analysis showed that the MMSE score was negatively correlated with the concentration of Aß1-40 (r2 = 0.764, p < 0.01), but positively related to the level of BDNF (r2 = 0.827, p < 0.01). Compared with those in control group, the content of serum cAMP and p-CREB in stroke patients was significantly decreased (p < 0.01), but the expression of p-Tau was statistically increased (p < 0.01). CONCLUSIONS: The cognitive function in stroke patients is impaired, with the rising content of serum Aß1-40 and reduction of BDNF, the mechanism of which is related to the decrease of cAMP and p-CREB and the increase of p-Tau. This provides a theoretical basis for searching the new therapeutic targets and new drugs for stroke.

Oral administration of short chain fatty acids could attenuate fat deposition of pigs.

Short chain fatty acids (SCFAs) are the main products of indigestible carbohydrates that are fermented by microbiota in the hindgut. This study was designed to investigate the effects of oral SCFAs administration on the lipid metabolism of weaned pigs. A total of 21 barrows were randomly allocated into three groups, including control group (orally infused with 200 mL physiological saline per day), low dose SCFAs group (orally infused with 200 mL SCFAs containing acetic acid 20.04 mM, propionic acid 7.71 mM and butyric acid 4.89 mM per day), and high dose SCFAs group (orally infused with 200 mL SCFAs containing acetic acid 40.08 mM, propionic acid 15.42 mM and butyric acid 9.78 mM per day). The results showed that the average daily feed intake of SCFAs groups were lower than that of control group (P<0.05). Oral administration of SCFAs decreased the concentrations of triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol and insulin (P<0.05), and increased the leptin concentration in serum (P<0.05). The total fat, as well as TC and TG levels in liver, was decreased by oral SCFAs administration (P<0.05). In addition, SCFAs down-regulated the mRNA expressions of fatty acid synthase (FAS) and sterol regulatory element binding protein 1c (P<0.05), and enhanced the mRNA expression of carnitine palmitoyltransferase-1α (CPT-1α) in liver (P<0.05). SCFAs also decreased FAS, acetyl-CoA carboxylase (ACC) and peroxisome proliferator activated receptor σ mRNA expressions in longissimus dorsi (P<0.05). And in abdominal fat, SCFAs reduced FAS and ACC mRNA expressions (P<0.05), and increased CPT-1α mRNA expression (P<0.05). These results suggested that oral administration of SCFAs could attenuate fat deposition in weaned pigs via reducing lipogenesis and enhancing lipolysis of different tissues.

MUC1 inhibition leads to decrease in PD-L1 levels via upregulation of miRNAs.

The PD-L1/PD-1 pathway is a critical component of the immunosuppressive tumor microenvironment in acute myeloid leukemia (AML), but little is known about its regulation. We investigated the role of the MUC1 oncoprotein in modulating PD-L1 expression in AML. Silencing of MUC1 in AML cell lines suppressed PD-L1 expression without a decrease in PD-L1 mRNA levels, suggesting a post-transcriptional mechanism of regulation. We identified the microRNAs miR-200c and miR-34a as key regulators of PD-L1 expression in AML. Silencing of MUC1 in AML cells led to a marked increase in miR-200c and miR-34a levels, without changes in precursor microRNA, suggesting that MUC1 might regulate microRNA-processing. MUC1 signaling decreased the expression of the microRNA-processing protein DICER, via the suppression of c-Jun activity. NanoString (Seattle, WA, USA) array of MUC1-silenced AML cells demonstrated an increase in the majority of probed microRNAs. In an immunocompetent murine AML model, targeting of MUC1 led to a significant increase in leukemia-specific T cells. In concert, targeting MUC1 signaling in human AML cells resulted in enhanced sensitivity to T-cell-mediated lysis. These findings suggest MUC1 is a critical regulator of PD-L1 expression via its effects on microRNA levels and represents a potential therapeutic target to enhance anti-tumor immunity.

Chemotherapy Plus Cetuximab versus Chemotherapy Alone for Patients with KRAS Wild Type Unresectable Liver-Confined Metastases Colorectal Cancer: An Updated Meta-Analysis of RCTs.

Purpose. Our study analyses clinical trials and evaluates the efficacy of adding cetuximab in systematic chemotherapy for unresectable colorectal cancer liver-confined metastases patients. Materials and Methods. Search EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials for RCTs comparing chemotherapy plus cetuximab with chemotherapy alone for KRAS wild type patients with colorectal cancer liver metastases (CRLMs). We calculated the relative risks (RRs) with 95% confidence interval and performed meta-analysis of hazard ratios (HRs) for the R0 resection rate, the overall response rate (ORR), the progression-free survival (PFS) and overall survival (OS). Results. 1173 articles were retrieved and 4 RCTs were available for our study. The four studies involved 504 KRAS wild type patients with CRLMs. The addition of cetuximab significantly improved all the 4 outcomes: the R0 resection rate (RR 2.03, p = 0.004), the ORR (RR 1.76, p < 0.00001), PFS (HR 0.63, p < 0.0001), and also OS (HR 0.74, p = 0.04); the last outcome is quite different from the conclusion published before. Conclusions. Although the number of patients analysed was limited, we found that the addition of cetuximab significantly improves the outcomes in KRAS wild type patients with unresectable colorectal cancer liver-confined metastases. Cetuximab combined with systematic chemotherapy perhaps suggests a promising choice for KRAS wild type patients with unresectable liver metastases.

Fast conversion of digital Fresnel hologram to phase-only hologram based on localized error diffusion and redistribution.

Past research has demonstrated that a digital, complex Fresnel hologram can be converted into a phase-only hologram with the use of the bi-direction error diffusion (BERD) algorithm. However, the recursive nature error diffusion process is lengthy and increases monotonically with hologram size. In this paper, we propose a method to overcome this problem. Briefly, each row of a hologram is partitioned into short non-overlapping segments, and a localized error diffusion algorithm is applied to convert the pixels in each segment into phase only values. Subsequently, the error signal is redistributed with low-pass filtering. As the operation on each segment is independent of others, the conversion process can be conducted at high speed with the graphic processing unit. The hologram obtained with the proposed method, known as the Localized Error Diffusion and Redistribution (LERDR) hologram, is over two orders of magnitude faster than that obtained by BERD for a 2048×2048 hologram, exceeding the capability of generating quality phase-only holograms in video rate.

Proteomic analysis of meningiomas.

Meningiomas represent one-third of all primary brain tumors and cause 35,000 new cases each year. Because of this high incidence, we sought to determine if there are proteomic differences between meningiomas and neighboring tissues. Two-dimensional gel electrophoresis and mass spectrometry were used to detect differentially expressed proteins in tumor samples, using arachnoid tissue as a control. Western blot analysis was used to validate the identified candidate proteins. We obtained quantitative data on 112 proteins, 17 of which were down-regulated and 26 of which were up-regulated in meningiomas relative to normal arachnoid tissue. Our analysis showed that the expression of galectin-3, vimentin, and endoplasmin was decreased significantly in meningiomas. The expression of 40S ribosomal protein S12, glutathione S-transferase P, and hypoxia up-regulated protein 1 was increased significantly (P < 0.05). The six above-mentioned differentially expressed proteins might be closely involved with the development of meningiomas. The results of this study provide basic insights into the proteome of meningiomas and provide a preliminary database for further research to enhance understanding of meningioma development.

Experimental investigation of cryogenic oscillating heat pipes.

A novel cryogenic heat pipe, oscillating heat pipe (OHP), which consists of an 4 × 18.5 cm evaporator, a 6 × 18.5 cm condenser, and 10 cm length of adiabatic section, has been developed and experimental characterization conducted. Experimental results show that the maximum heat transport capability of the OHP reached 380W with average temperature difference of 49 °C between the evaporator and condenser when the cryogenic OHP was charged with liquid nitrogen at 48% (v/v) and operated in a horizontal direction. The thermal resistance decreased from 0.256 to 0.112 while the heat load increased from 22.5 to 321.8 W. When the OHP was operated at a steady state and an incremental heat load was added to it, the OHP operation changed from a steady state to an unsteady state until a new steady state was reached. This process can be divided into three regions: (I) unsteady state; (II) transient state; and (III) new steady state. In the steady state, the amplitude of temperature change in the evaporator is smaller than that of the condenser while the temperature response keeps the same frequency both in the evaporator and the condenser. The experimental results also showed that the amplitude of temperature difference between the evaporator and the condenser decreased when the heat load increased.

The transcription factor early growth-response factor 1 modulates tumor necrosis factor-alpha, immunoglobulin E, and airway responsiveness in mice.

Early growth-response factor 1 (Egr-1) is a sequence-specific transcription factor that plays a regulatory role in the expression of many genes important in inflammation, cell growth, apoptosis, and the pathogenesis of disease. In vitro studies suggest that Egr-1 is capable of regulating the expression of tumor necrosis factor-alpha (TNF-alpha) and other genes involved in airway inflammation and reactivity following allergen stimulation. On the basis of these data, we hypothesized that in the absence of Egr-1, the TNF-alpha response and subsequent downstream inflammatory events that usually follow allergen challenge would be diminished. To test our hypothesis Egr-1 knock-out (KO) mice were examined in an ovalbumin (OVA)-induced model of airway inflammation and reactivity, and compared with identically treated wild-type (WT) control mice. In response to OVA sensitization and airway challenge, KO mice had diminished TNF-alpha mRNA and protein in the lungs and mast cells compared with WT mice. Interestingly, the KO mice had elevated IgE levels at baseline and after allergen challenge compared with WT mice. Furthermore, the airways of KO mice were hyporesponsive to methacholine challenge at baseline and after allergen challenge. These data indicate that Egr-1 modulates TNF-alpha, IgE, and airway responsiveness in mice.

Quantitative trait locus mapping of airway responsiveness to chromosomes 6 and 7 in inbred mice.

Quantitative trait locus (QTL) mapping was used to identify chromosomal regions contributing to airway hyperresponsiveness in mice. Airway responsiveness to methacholine was measured in A/J and C3H/HeJ parental strains as well as in progeny derived from crosses between these strains. QTL mapping of backcross [(A/J x C3H/HeJ) x C3H/HeJ] progeny (n = 137-227 informative mice for markers tested) revealed two significant linkages to loci on chromosomes 6 and 7. The QTL on chromosome 6 confirms the previous report by others of a linkage in this region in the same genetic backgrounds; the second QTL, on chromosome 7, represents a novel locus. In addition, we obtained suggestive evidence for linkage (logarithm of odds ratio = 1.7) on chromosome 17, which lies in the same region previously identified in a cross between A/J and C57BL/6J mice. Airway responsiveness in a cross between A/J and C3H/HeJ mice is under the control of at least two major genetic loci, with evidence for a third locus that has been previously implicated in an A/J and C57BL/6J cross; this indicates that multiple genetic factors control the expression of this phenotype.

Targeted deletion of the neutral endopeptidase gene alters ventilatory responses to acute hypoxia in mice.

Neutral endopeptidase (NEP) is one of the major endopeptidases responsible for the inactivation of substance P in the carotid body, a neurotransmitter shown to be important in the transduction of hypoxic stimuli. Ventilatory responses to acute hypoxia were measured by indirect plethysmography in unanesthetized, unrestrained wild-type mice and in mice in which the NEP gene was deleted (NEP -/-). Ventilation was measured while the animals breathed room air: 12% O(2) in N(2) and 8% O(2) in N(2). Deletion of the NEP gene caused marked alterations in both the magnitude and composition of the hypoxic ventilatory response to both 8% O(2) in N(2) and 12% O(2) in N(2), compared with the wild-type mice (C57BL/6J) on the same genetic background as the NEP -/- mice. Treatment of C57BL/6J mice with thiorphan, a NEP inhibitor, resulted in a greater ventilatory response to 8% O(2) because of a significantly greater shortening of expiratory time. The results of these studies demonstrate that NEP plays an important role in modifying the expression of the ventilatory response to acute hypoxia.

Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma.

Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma.

Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammation.

We examined the role of the interleukin-8 (IL-8) receptor in a murine model of allergen-induced pulmonary inflammation using mice with a targeted deletion of the murine IL-8 receptor homologue (IL-8r-/-). Wild-type (Wt) and IL-8r-/- mice were systemically immunized to ovalbumin (OVA) and were exposed with either single or multiple challenge of aerosolized phosphate-buffered saline (OVA/PBS) or OVA (OVA/OVA). Analysis of cells recovered from bronchoalveolar lavage (BAL) revealed a diminished recruitment of neutrophils to the airway lumen after single challenge in IL-8r-/- mice compared with Wt mice, whereas multiply challenged IL-8r-/- mice had increased B cells and fewer neutrophils compared with Wt mice. Both Wt and IL-8r-/- OVA/OVA mice recruited similar numbers of eosinophils to the BAL fluid and exhibited comparable degrees of pulmonary inflammation histologically. Both total and OVA-specific IgE levels were greater in multiply challenged IL-8r-/- OVA/OVA mice than in Wt mice. Both the IL-8r-/- OVA/OVA and OVA/PBS mice were significantly less responsive to methacholine than their respective Wt groups, but both Wt and IL-8r mice showed similar degrees of enhancement after multiple allergen challenge. The data demonstrate that the IL-8r modulates IgE production, airway responsiveness, and the composition of the cells (B cells and neutrophils) recruited to the airway lumen in response to antigen.

Contribution of type I NOS to expired gas NO and bronchial responsiveness in mice.

Nitric oxide (NO) can be measured in the expired gas of humans and animals, but the source of expired NO (F(E)NO) and the functional contribution of the various known isoforms of NO synthase (NOS) to the NO measured in the expired air is not known. F(E)NO was measured in the expired air of mice during mechanical ventilation via a tracheal cannula. F(E)NO was significantly higher in wild-type B6SV129J +/+ mice than in mice with a targeted deletion of type I (neural) NOS (nNOS, -/-) (6.3 +/- 0.9 vs. 3.9 +/- 0.4 parts/billion, P = 0.0345, for +/+ and -/- mice, respectively), indicating that approximately 40% of the NO in expired air in B6SV129 mice is derived from nNOS. Airway responsiveness to methacholine (MCh), assessed by the log of the effective dose of MCh for a doubling of pulmonary resistance from baseline (ED(200)R(L)), was significantly lower in the -/- nNOS mice than in the wild-type mice (logED(200)R(L), 2.24 +/- 0.07 vs. 2.51 +/- 0.06 microg/kg, respectively; P = 0.003). These findings indicate that nNOS significantly contributes to baseline F(E)NO and promotes airway hyperresponsiveness in the mouse.

Reduction of allergic airway responses in P-selectin-deficient mice.

P-selectin is an adhesion receptor that has been shown to be important in the recruitment of eosinophils and lymphocytes in a variety of inflammatory conditions. Because cellular recruitment is thought to be a critical event in allergen-induced changes in airway responsiveness, we reasoned that P-selectin-deficient mice would exhibit reduced airway responsiveness and cellular trafficking noted in wild-type (+/+) mice. Both (+/+) and P-selectin-deficient (-/-) mice sensitized and challenged with ovalbumin (OVA/OVA) exhibited the same capacity to produce increased titers of total and OVA-specific immunoglobulin E. Airway responsiveness to methacholine was significantly greater in the (+/+) (OVA/OVA) animals than it was in the respective (-/-) (OVA/OVA) group or control groups (P = 0.0016). Bronchoalveolar lavage fluid from (-/-) (OVA/OVA) mice contained significantly fewer eosinophils and lymphocytes compared with the (+/+) (OVA/OVA) mice (P < 0.05). These results suggest that the predominant role of P-selectin in OVA-induced airway hyperresponsiveness is to promote the airway inflammatory response to allergen inhalation.