[Emphasis on the prevention and treatment of hepatic vascular diseases].

Portal hypertension, as a common and complex hepatic vascular disease, is a key pathophysiological link in many events of acute cirrhosis decompensation and the progression of multiple organ failure. The most effective measure to reduce portal hypertension is a transjugular intrahepatic portosystemic shunt (TIPS). Maintaining liver function, reducing complications, and improving patients' quality of life and survival time are positively impacted by early TIPS insertion. Patients with cirrhosis have a risk of portal vein thrombosis (PVT) that is 1 000 times higher than that of the normal population. Hepatic sinusoidal obstruction syndrome has a severe clinical course and a high mortality risk. The primary treatment approaches for PVT and HSOS are anticoagulation and TIPS. The innovative magnetic anastomosis vascular technique significantly shortens the anhepatic time and restores normal liver function in patients following liver transplantation.

[Expert consensus for diagnosis and treatment of thrombocytopenia in China].

Thrombocytopenia is the main clinical manifestation or common complication of multiple diseases, but there is still a lack of systematic understanding of pathogenesis, underlying diseases and treatment strategies of thrombocytopenia. Based on evidence-based medicine, this consensus summarizes seven aspects related to thrombocytopenia, including definition, epidemiology, pathogenesis, clinical manifestations, laboratory examination, diagnosis and treatment. This consensus provides an important reference for the diagnosis and treatment of thrombocytopenia.

Glycolipid-peptide conjugate vaccines enhance CD8+ T cell responses against human viral proteins.

An important goal of vaccination against viruses and virus-driven cancers is to elicit cytotoxic CD8+ T cells specific for virus-derived peptides. CD8+ T cell responses can be enhanced by engaging help from natural killer T (NKT) cells. We have produced synthetic vaccines that induce strong peptide-specific CD8+ T cell responses in vivo by incorporating an NKT cell-activating glycolipid. Here we examine the effect of a glycolipid-peptide conjugate vaccine incorporating an NKT cell-activating glycolipid linked to an MHC class I-restricted peptide from a viral antigen in human peripheral blood mononuclear cells. The vaccine induces CD1d-dependent activation of human NKT cells following enzymatic cleavage, activates human dendritic cells in an NKT-cell dependent manner, and generates a pool of activated antigen-specific CD8+ T cells with cytotoxic potential. Compared to unconjugated peptide, the vaccine upregulates expression of genes encoding interferon-γ, CD137 and granzyme B. A similar vaccine incorporating a peptide from the clinically-relevant human papilloma virus (HPV) 16 E7 oncoprotein induces cytotoxicity against peptide-expressing targets in vivo, and elicits a better antitumor response in a model of E7-expressing lung cancer than its unconjugated components. Glycolipid-peptide conjugate vaccines may prove useful for the prevention or treatment of viral infections and tumors that express viral antigens.

N1-guanyl-1,7-diaminoheptane enhances the chemosensitivity of NSCLC cells to cetuximab through inhibition of eukaryotic translation initiation factor 5A2 activation.

OBJECTIVE: N1-guanyl-1, 7-diaminoheptane (GC7), an inhibitor of deoxyhypusine synthase has been shown to exhibit significant anti-cancer activity. However, the biological role of eukaryotic translation initiation factor 5A2 activation (EIF5A2) and GC7 on drug resistance in non-small cell lung cancer (NSCLC) has not been investigated. In this study, we aimed to investigate the therapeutic effect of GC7 combined with cetuximab in NSCLC therapy. MATERIALS AND METHODS: The current study used cell viability assays, EdU incorporation assays, and western blot to detect that the GC7 exhibited synergistic cytotoxicity with cetuximab in NSCLC. RESULTS: CCK-8 assays showed that combined treatment with GC7 and cetuximab significantly inhibited the viabilities in three NSCLC cell lines. In addition, EdU incorporation assays also indicated that GC7 co-treatment remarkably enhanced the cetuximab sensitivity in NSCLC cells. Nevertheless, down-regulation of EIF5A2 diminished the regulatory role of GC7 in cetuximab cytotoxicity. Western blot showed that transfection of EIF5A2 siRNA significantly suppressed the protein expression of EIF5A2 in NSCLC cells. CONCLUSIONS: These findings demonstrate that combined treatment with GC7 could enhance cetuximab sensitivity by inhibiting EIF5A2 in NSCLC cells, implying the potential clinical application of GC7 in cetuximab-based chemotherapy for NSCLC patients.

Vasoactive intestinal polypeptide suppresses proliferation of human cord blood-derived hematopoietic progenitor cells by increasing TNF-α and TGF-ß production in the liver.

The physiology of hepatic hematopoiesis is largely unknown, although studies have indicated that vasoactive intestinal polypeptide (VIP) is involved in this disease. To validate this hypothesis, we assessed the effects of VIP on human cord blood CD34+ cells. We also measured VIP levels and the capacity of vasoactive intestinal polypeptide receptor (VIPR) to bind to VIP in the rat liver during different developmental phases. VIP inhibited the proliferation of cord blood-derived CD34(+) cells from concentrations of 10-7-10-12 M. The highest suppression was achieved with 10-8 M VIP at day 10. Intracellular levels of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-ß1 in CD34(+) cells treated with VIP were increased by 50.70 and 43.46%, respectively. Variations in VIP levels in the rat fetal liver generally increased rapidly with the stage of fetal development. In addition, the affinity of VIPR for VIP increased from relatively low levels in the rat fetal liver and peaked at birth, after which it gradually decreased. VIP had a suppressive effect on the proliferation of human cord blood-derived CD34(+) cells, partially by increasing the production of TNF-α and TGF-ß. Low VIP levels in the fetal liver and gradually increasing levels after birth may in part be responsible for suppressing hematopoietic stem cell and progenitor proliferation in the liver.

Roles of cellular polyamines in mucosal healing in the gastrointestinal tract.

The mammalian gastrointestinal (GI) mucosa is a rapidly self-renewing tissue in the body, and its integrity is preserved through the strict regulation of epithelial cell proliferation, growth arrest, and apoptosis. Polyamines are shown to play an important role in the regulation of gastrointestinal mucosal growth and healing after injury under physiological and various pathological conditions. In this review, we highlight the importance of cellular polyamines in the control GI mucosal proliferation, migration, apoptosis, angiogenesis and GI barrier function during mucosal repair after injury.

Octreotide alleviates obesity by reducing intestinal glucose absorption and inhibiting low-grade inflammation.

PURPOSE: To investigate the role of octreotide, a somatostatin (SST) analog with anti-inflammatory effects, on the digestive and absorptive functions of jejunum in rats fed a high-fat diet, as well as its therapeutic prospects for diet-induced obesity. METHODS: Rats were divided into three groups with different diet and treatment for the 176-day experiment: (1) control, 18 rats fed with standard chow, (2) high-fat control, 19 rats fed with high-fat chow, and (3) high-fat octreotide, 21 rats fed with high-fat chow and treated with octreotide for the last 8 days of the experiment. Plasma tumor necrosis factor-α (TNF-α) was measured by ELISA and SST by radioimmunoassay. Disaccharidase activity in the jejunal homogenate was determined. SST and Na⁺-dependent glucose transporter 1 (SGLT-1) in the jejunal mucosa were visualized by immunohistochemistry. SGLT-1 was quantified by reverse transcription polymerase chain reaction and Western blot assays. RESULTS: After 176 days, the fat/body weight ratio, villus height, maltase, SGLT-1, and plasma TNF-α in the high-fat control rats were much higher than those in the control rats (p < 0.01 or p < 0.05) and were significantly lower in the high-fat + octreotide rats (p < 0.01 or p < 0.05). SST levels were dramatically different in the intestinal mucosa of the two high-fat groups (231.12 ± 98.18 pg/mg in the high-fat controls and 480.01 ± 286.65 pg/mg in the octreotide group). CONCLUSIONS: The low-grade inflammation induced by high-fat diet apparently reduced the secretion of intestinal SST, which increased intestinal absorption of energy and nutrients and formation of adipose tissues. Octreotide effectively reversed this process, a finding that has far-reaching significance for the regulation of energy balance.

Polysaccharides of Dendrobium officinale inhibit TNF-α-induced apoptosis in A-253 cell line.

OBJECTIVE: Our previous study demonstrated that polysaccharides of Dendrobium officinale Kimura et Migo (DP) were capable of enhancing immunomodulation in an experimental model of Sjögren's syndrome, a chronic autoimmune disease mainly affecting the salivary glands. In the present study, we further investigated the protective effect of DP on a human salivary gland cell line A-253 against tumor necrosis factor (TNF)-α-induced apoptosis. MATERIALS: TNF-α (100 U/ml) was used as the stimulus for treating the A-253 cells to induce cellular apoptosis. Nuclear factor-kappa B (NF-κB, p65), phosphorylation of mitogen-activated protein kinases (MAPK), reactive oxygen species (ROS) generation, mitochondrial membrane potential and proapoptotic proteins were examined. A-253 cells were pre-treated with DP for 12 h before TNF-α stimulation. RESULTS: We observed translocation of NF-κB into the nuclei, prolonged MAPK, excessive ROS generation and strongly decreased mitochondrial membrane potential, and subsequently cytochrome C release and caspase-3 activation. However, pre-treatment with DP significantly inhibited the TNF-α-induced apoptotic factors. CONCLUSIONS: Our data suggested the inhibitory effect of DP on TNF-α-induced apoptosis in a human salivary gland cell line. This inhibition indicated potential inference of DP in the initial plasma membrane-bound complex of TNF-α and its receptors.

Disturbances of mesenteric lymph flow and in vivo intestinal lymphocyte trafficking during early gut injury induced by ischemia-reperfusion in rats.

We sought to define the role of mesenteric lymph in the generation of remote organ damage at the early stage of gut ischemia-reperfusion (I/R) injury. The measurement of mesenteric lymph flow was carried out by cannulation of mesenteric lymphatics. The distribution of in vivo intestinal lymphocyte trafficking was performed by 51Cr labeled lymphocyte and measurement of 51Cr-lymphocytes distribution by gamma-counter. Endotoxin concentration was assayed using the limulus test kit and TNF-alpha level was detected by ELISA. After gut I/R injury, the volumes of lymph flow in mesenteric lymphatics per hour were sharply decreased by 72% and the number of intestinal lymphocytes per milliliter was decreased by 61%, which led to the intestinal lymphocyte output per hour significantly decreased by 90% (predominantly T cells), while the population of 51Cr-lymphocytes in Peyer's patches, small intestine (except Peyer's patches), mesenteric nodes, large intestine, and stomach increased by 87%, 191%, 87%, 266%, 262%, respectively. Meanwhile, endotoxin and TNF-alpha levels in mesenteric lymph were significantly increased. These findings demonstrate the marked disorders of mesenteric lymph flow and in vivo intestinal lymphocytes migration and the accompanying increase of endotoxin and TNF-alpha levels in mesenteric lymph in the early stage of gut I/R injury.

Stenting versus medical treatment for severe symptomatic intracranial stenosis.

BACKGROUND AND PURPOSE: Intracranial atherosclerosis is especially prevalent in Asians, but intracranial stent placement and medical treatment for severe intracranial stenosis are controversial. Thus, we compared long-term outcomes of these 2 therapeutic approaches in an Asian population. MATERIALS AND METHODS: Patients with angiographically proved severe (≥70%) symptomatic intracranial atherosclerosis, with or without stent placement, were retrospectively reviewed at a single center between 2002 and 2009, with adjustments for age, sex, vascular risk factors, degree of baseline stenosis, and baseline functional status. RESULTS: Of the 114 patients followed from 3 to 36 months (mean, 17.3 months) after initial diagnosis, 53 received 56 stents in addition to medical treatment (stent-placement group), and 61 matched patients received only medical treatment (medical group). Total clinical events, including stroke, TIA, and vascular death, were 12 (22.6%) and 15 (24.6%) in the stent-placement and medical groups, respectively (P = .99). The stent-placement group had significantly better functional outcomes than the medical group (94.3% versus 78.7% for mRS scores of 0-3, P = .045). Most events in the stent-placement group occurred within the first week of the periprocedural period (17.0%) as minor embolic or perforator infarctions, and the rate of events decreased thereafter (5.7%, P = .07). Stent placement over the perforator-rich MCA and BA independently predicted periprocedural events on multivariate regression analysis. In the medical group, events increased in frequency (21.7%) and severity with time. CONCLUSIONS: Although the total ischemic event rate was similar in the 2 groups during a 3-year follow-up, the stent-placement group had a more favorable functional outcome despite minor periprocedural strokes.

Microscopic polyangiitis presenting with capsular warning syndrome and subsequent stroke.

A 55-year-old man developed ischemic stroke after three episodes of transient dysarthria and left hemiplegia, a typical manifestation of capsular warning syndrome. Magnetic resonance imaging of the brain showed bilateral basal ganglionic infarction. The patient had no significant risk of stroke. However, the systemic manifestations, an elevated titer of perinuclear anti-neutrophilic cytoplasmic antibody and a skin biopsy revealing leukocytoclastic venulitis confirmed the undrlying microscopic polyangiitis.

Pediatric foot fractures: evaluation and treatment.

Foot fractures account for 5% to 8% of all pediatric fractures and for approximately 7% of all physeal fractures. A thorough understanding of the anatomy of the child's foot is of central importance when treating these injuries. Due to the difficulties that may be encountered in obtaining an accurate physical examination of a child with a foot injury and the complexities of radiographic evaluation of the immature foot, a high index of suspicion for the presence of a fracture facilitates early and accurate diagnosis. Although the treatment results in pediatric foot trauma are generally good, potential pitfalls in the treatment of Lisfranc fractures, talar neck and body fractures, and lawn mower injuries to the foot must be anticipated and avoided if possible.

Elbow aspiration and arthrogram: an alternative method.

We describe a posterior elbow-aspiration approach that is safe, easy, and effective in all settings, including trauma.

Use of P wave configuration during atrial tachycardia to predict site of origin.

OBJECTIVES: This study sought to construct an algorithm to differentiate left atrial from right atrial tachycardia foci on the basis of surface electrocardiograms (ECGs). BACKGROUND: Atrial tachycardia is an uncommon form of supraventricular tachycardia, often resistant to drug therapy. METHODS: A total of 31 consecutive patients with atrial tachycardia due to either abnormal automaticity or triggered rhythm underwent detailed atrial endocardial mapping and successful radiofrequency catheter ablation of a single atrial focus. P wave configuration was analyzed from 12-lead ECGs during tachycardia during either spontaneous or pharmacologically induced atrioventricular block. P waves inscribed above the isoelectric line (TP interval) were classified as positive, below as negative, above and below (or conversely, below and above) as biphasic and flat P waves as isoelectric (0). In 17 patients the tachycardia was located in the right atrium: crista terminalis (n = 4); right atrial appendage (n = 4); lateral wall (n = 4); posteroinferior right atrium (n = 3); tricuspid annulus (n = 1); and near the coronary sinus (n = 1). In 14 patients, atrial tachycardia was located in the left atrium: at the entrance of the right (n = 6) or left (n = 4) superior pulmonary veins; left inferior pulmonary vein (n = 1); inferior left atrium (n = 1); base of left atrial appendage (n = 1); and high lateral left atrium (n = 1). RESULTS: There were no differences in P wave vectors between sites at the right atrial lateral wall versus the right atrial appendage or between sites at the entrance of right versus left superior pulmonary veins. However, analysis of P wave configuration showed that leads aVL and V1 were most helpful in distinguishing right atrial from left atrial foci. The sensitivity and specificity of using a positive or biphasic P wave in lead aVL to predict a right atrial focus was 88% and 79%, respectively. The sensitivity and specificity of a positive P wave in lead V1 in predicting a left atrial focus was 93% and 88%, respectively. CONCLUSIONS: 1) Analyses of surface P wave configuration proved to be reasonably good in differentiating right atrial from left atrial tachycardia foci. 2) Leads II, III and aVF were helpful in providing clues for differentiating superior from inferior foci.