Preoperative high level of D-dimers predicts unresectability of pancreatic head cancer

AIM: To assess the value of D-dimer level in determining resectability of pancreatic cancer.

Immunopathogenesis of chronic hepatitis B

Chronic hepatitis B (CHB) is a widespread infectious disease with unfavorable outcomes and life-threatening consequences for patients, in spite of modern vaccination and antiviral treatment modalities. Cutting-edge experimental approaches have demonstrated key pathways that involve cross-talk between viral particles and host immune cells. All events, including penetration of hepatitis B virus (HBV) particles into host cells, establishing persistence, and chronization of CHB infection, and possibility of complete elimination of HBV particles are controlled by the immune system. Researchers have paid special attention to the replication capacity of HBV in host cells, which is associated with cellular changes that reflect presentation of viral antigens and variability of HBV antigen features. In addition, specific HBV proteins have an immune-modulating ability to initiate molecular mechanisms that “avoid” control by the immune system. The relationship between immunological shifts and chronic infection stages has been intensively studied since it was recognized that the immune system is a direct participant in the recurrent (cyclic) nature of CHB. Understanding the wide diversity of molecular pathways and the crosstalk between innate and adaptive immune system components will provide fresh insight into CHB immune pathogenesis and the possibilities of developing new treatment strategies for this disease.

Molecularly defined adult-type hypolactasia in school-aged children with a previous history of cow's milk allergy

AIM： To assess the role of lactase non-persistence/per- sistence in school-aged children and their milk-related symptoms. METHODS： The genotypes for the C/T-13910 variant associated with lactase non-persistence/ persistence were determined using PCR-minisequencing in a group of 172 children with a mean age of 8.6 years （SE = 0.02, 93 boys） participating in a follow-up study for cow＇s milk allergy. The parents were asked to assess their children＇s milk consumption and abdominal symptoms. RESULTS： The presence of allergy to cow＇s milk was not associated with the C/C-13910 genotype related with a decline of lactase enzyme activity during childhood （lactase non-persistence）. The frequency of the C/C-13910 genotype （16%） was similar to published figures for the prevalence of adult-type hypolactasia in Finland. The majority of the children （90%） in this series consumed milk but 26% of their families suspected that their children had milk-related symptoms. Forty-eight percent of the children with the C/C-13910 genotype did not drink milk at all or consumed a low lactose containing diet prior to the genotyping （P〈 0.004 when compared to the other genotypes）. CONCLUSION： Analysis of the C/T-13910 polymorphism is an easy and reliable method for excluding adult-type hypolactasia in children with milk-related symptoms. Genotyping for this variant can be used to advise diets for children with a previous history of cow＇s milk allergy.

Cross-reactivity between aeroallergens and food allergens

In patients with respiratory allergy,cross-reactivity between aeroallergens and foods may induce food allergy,symptoms ranging from oral allergy syndrome to severe anaphylaxis.Clinical entities due to Ig E sensitization to cross-reactive aeroallergen and food allergen components are described for many sources of plant origin(pollen-food syndromes and associations,such as birch-apple,cypress-peach and celery-mugwortspice syndromes,and mugwort-peach,mugwortchamomile,mugwort-mustard,ragweed-melon-banana,goosefoot-melon associations),fungal origin(Alternariaspinach syndrome),and invertebrate,mammalian or avian origin(mite-shrimp,cat-pork,and bird-egg syndromes).Clinical cases of allergic reactions to ingestion of food products containing pollen grains of specific plants,in patients with respiratory allergy to Asteraceae pollen,especially mugwort and ragweed,are also mentioned,for honey,royal jelly and bee polen dietary supplements,along with allergic reactions to foods contaminated with mites or fungi in patients with respiratory allergy to these aeroallergens.Medical history and diagnosis approach may be guided by the knowledge about the diverse cross-reacting allergens involved,and by the understanding of these clinical entities which may vary significantly or may be overlapping.The association between primary Ig E sensitization with respiratory symptoms to inhaled allergens and food allergy due to cross-reactive allergen components is important to assess in allergy practice.The use of molecular-based diagnosis improves the understanding of clinically relevant Ig E sensitization to cross-reactive allergen components from aeroallergen sources and foods.

Early stent thrombosis secondary to food allergic reaction:Kounis syndrome following rice pudding ingestion

Kounis syndrome is the concurrence of coronary spasm, acute myocardial infarction or stent thrombosis, with allergic reactions in the setting of mast-cell and platelet activation. In this report Kounis syndrome manifesting as stent thrombosis with left ventricular thrombus formation was triggered by a food-induced allergic reaction. The allergic reaction to food was confirmed by oral rice pudding ingredients challenge test while skin tests were inconclusive. To our knowledge, this is first report of early stent thrombosis secondary to food allergic reaction in a 70-year-old man patient who was found to have left ventricular thrombus and undiagnosed hypertrophic cardiomyopathy.

Molecular diagnosis in cat allergy

Domestic cats represent one of the most common sources of indoor allergens.All over the world,many households own cats,whose allergens are persistent and widespread.Cat allergy itself is frequent,and its symptoms vary from rhinoconjunctivitis to life-threatening asthma.In vitro diagnosis using precision medicine allergy immunoassays is important because natural cat dander extracts may differ in quality and quantity of some of the individual allergen components and other molecules.In the component-resolved diagnosis of cat allergy,singleplex and multiplex specific immunoglobulin(Ig)E assays include use of the cat-specific major allergen,secretoglobin Fel d 1(as a species-specific molecule),other allergen components(such as lipocalins Fel d 4,cross-reacting with other animal similar molecules,and Fel d 7,present in small quantities in natural extracts),and serum albumin Fel d 2(related to the cat-pork syndrome).IgA Fel d 5 and IgM Fel d 6 are not available as allergen components in the current commercial IgE immunoassays,but they may impair the in vitro diagnostic evaluation of cat allergy because galactose-α1,3-galactose is an IgE-binding epitope of these native feline allergens.The benefits of molecular-based cat allergy diagnosis are continually evaluated,as the role of recombinant allergen components already known is detailed and new other molecules of interest may be discovered in the future.

Precision medicine allergy immunoassay methods for assessing immunoglobulin E sensitization to aeroallergen molecules

Molecular-based allergy diagnosis for the in vitro assessment of a patient immunoglobulin E(IgE) sensitization profile at the molecular level uses allergen molecules(also referred to as allergen components), which may be well-defined, highly purified, natural allergen components or recombinant allergens. Modern immunoassay methods used for the detection of specific Ig E against aeroallergen components are either singleplex(such as the fluorescence enzyme immunoassay with capsulated cellulose polymer solid-phase coupled allergens, the enzyme-enhanced chemiluminescence immunoassay and the reversed enzyme allergosorbent test, with liquid-phase allergens), multiparameter(such as the line blot immunoassay for defined partial allergen diagnostics with allergen components coating membrane strips) or multiplex(such as the microarraybased immunoassay on immuno solid-phase allergen chip, and the two new multiplex nanotechnology-based immunoassays: the patient-friendly allergen nanobead array, and the macroarray nanotechnology-based immunoassay used as a molecular allergy explorer). The precision medicine diagnostic work-up may be organized as an integrated "U-shape" approach, with a "top-down" approach(from symptoms to molecules) and a "bottomup" approach(from molecules to clinical implications), as needed in selected patients. The comprehensive and accurate Ig E sensitization molecular profiling, with identification of the relevant allergens, is indicated within the framework of a detailed patient's clinical history to distinguish genuine Ig E sensitization from sensitization due to cross-reactivity(especially in polysensitized patients), to assess unclear symptoms and unsatisfactory response to treatment, to reveal unexpected sensitizations, and to improve assessment of severity and risk aspects in some patients. Practical approaches, such as anamnesis molecular thinking, laboratory molecular thinking and postmolecular anamnesis, are sometimes applied. The component-resolved diagnosis of the specific IgE repertoire has a key impact on optimal decisions making for prophylactic and specific immunotherapeutic strategies tailored for the individual patient.

Molecular biomarkers for grass pollen immunotherapy

Grass pollen allergy represents a significant cause of allergic morbidity worldwide. Component-resolved diagnosis biomarkers are increasingly used in allergy practice in order to evaluate the sensitization to grass pollen allergens, allowing the clinician to confirm genuine sensitization to the corresponding allergen plant sources and supporting an accurate prescription of allergy immunotherapy(AIT), an important approach in many regions of the world with great plant biodiversity and/or where pollen seasons may overlap. The search for candidate predictive biomarkers for grass pollen immunotherapy(tolerogenic dendritic cells and regulatory T cells biomarkers, serum blocking antibodies biomarkers, especially functional ones, immune activation and immune tolerance soluble biomarkers and apoptosis biomarkers) opens new opportunities for the early detection of clinical responders for AIT, for the follow-up of these patients and for the development of new allergy vaccines.

Celiac Disease in a Patient with Baker’s Asthma and Wheat Allergy Due to Tri a 14

We describe the case of a patient that developed persistent severe asthma after having started to work in a bakery. The subsequent appearance of gastrointestinal symptoms was diagnosed as celiac disease (CD). She also experienced severe asthma attacks when cooking pasta, and expe-rienced anaphylactic shock a few minutes after wheat flour inhalation. The allergologic workup was positive for several cereal products and Tri a 14 (Tricum aestivum 14), while specific IgE titer to Pru p 3 (Prunus persica 3) was negative. Our patient had no recurrence of these episodes when she avoided cooking wheat flour products and wheat in processed foods. The pathogenic mechanisms underlying CD and IgE-mediated food allergy are different and the coexistence of both diseases seems to be rare. Tri a 14 is the major wheat allergen involved in our case;this allergen can sensitize through the respiratory and the oral route, and can give way to anaphylaxis. A possible role played by interleukin-15 (IL-15) and interleukin-21 (IL-21) in the induction of IgE-mediate hypersensitivity, as well as in the pathogenesis of CD, is prospected and discussed briefly herein.

Involvement and therapeutic implications of airway epithelial barrier dysfunction in type 2 inflammation of asthma

Type 2 inflammation is a complex immune response and primary mechanism for several common allergic diseases including allergic rhinitis,allergic asthma,atopic dermatitis,and chronic rhinosinusitis with nasal polyps.It is the predominant type of immune response against helminths to prevent their tissue infiltration and induce their expulsion.Recent studies suggest that epithelial barrier dysfunction contributes to the development of type 2 inflammation in asthma,which may partly explain the increasing prevalence of asthma in China and around the globe.The epithelial barrier hypothesis has recently been proposed and has received great interest from the scientific community.The development of leaky epithelial barriers leads to microbial dysbiosis and the translocation of bacteria to inter-and sub-epithelial areas and the development of epithelial tissue inflammation.Accordingly,preventing the impairment and promoting the restoration of a deteriorated airway epithelial barrier represents a promising strategy for the treatment of asthma.This review introduces the interaction between type 2 inflammation and the airway epithelial barrier in asthma,the structure and molecular composition of the airway epithelial barrier,and the assessment of epithelial barrier integrity.The role of airway epithelial barrier disruption in the pathogenesis of asthma will be discussed.In addition,the possible mechanisms underlying the airway epithelial barrier dysfunction induced by allergens and environmental pollutants,and current treatments to restore the airway epithelial barrier are reviewed.

Mutation analysis of p63 gene in the first Chinese family with ADULT syndrome

Background ADULT syndrome （acro-dermato-ungual-lacrimal-tooth syndrome） is a rare ectodermal dysplasia disorder known as autosomal dominant inheritance. Recent studies have linked p63 gene mutation to the development of this disease. However, the genetic characteristics of ADULT syndrome were still not well understood. Methods Mutation analysis of p63 gene in the first Chinese ADULT syndrome family was performed using direct DNA sequencing. Results The sequence analysis of exon 8 of p63 gene disclosed a heterozygous G〉A substitution at nucleotide 893 （R298Q） in the proband. In addition, a single nucleotide polymorphism （SNP） rs16864880 in the downstream flanking region （DFR） of p63 exon 8 was also identified in this family. The proband and the paternal side including her father exhibited the C/G genotype at this position. The C/G variant frequency in the paternal was significantly higher as compared with the maternal （6/10 vs 0/6, P=0.034）. Conclusions ADULT syndrome may be caused by the p63 gene mutation, and it might have closer genetic association with the paternal side in this family.

Quercetin in combating H2O2 induced early cell apoptosis and mitochondrial damage to normal human keratinocytes

Background Oxidative stress plays an important role in the pathogenesis of epidermal diseases. This study aimed to investigate the effects of quercetin on the anti-oxidative response and on mitochondrial protection in cultured normal human keratinocytes. Methods Cultured HaCaT cells were treated with different concentrations of H202 （0, 50, 100, 250, 500 pmol/L） for different periods of time （0.5, 1, 2, 4 hours） to establish an oxidative stress model. The cultured HaCaT cells were randomly assigned to control, H2O2, and quercetin＋H2O2 groups. For the quercetin groups, the cells were treated with different concentrations of quercetin （0, 10, 25, 50 umol/L） before exposure to H2O2. Morphological changes of the cells were observed under an inverted microscope and an electron microscope. The cell viability was detected by the MIF method. The cell apoptosis （AnnexinV/propidium iodide double stain） and mitochondrial membrane potential （△ψm） changes were detected by flow cytometry. Results An oxidative stress model of HaCaT cells was established under a suitable concentration （250 umol/L） and treated time of H2O2 （2 hours）. The cell viability and △ψm decreased in a concentration-dependent and time-dependent manner while the percentage of apoptotic cells significantly increased in the H2O2 groups compared with the control group （P 〈0.05）. The cell viability and △ψm of the quercetin treated group increased （P 〈0.05） and the percentage of apoptotic cells decreased at concentrations of 1-50 umol/L quercetin （P 〈0.01） compared with H2O2 treated group. Conclusion Quercetin can relieve the cell damage and apoptosis from H2O2 induced injury to HaCaT cells by anti-oxidation and mitochondrial protection.