AIM: To investigate the relationship between serum soluble E-selectin (sE-selectin) and insulin resistance, serum uric acid, serum lipid in essential hypertension patients. METHODS: Fasting serum sE-selectin concentration, plasma glucose, serum insulin, serum uric acid, total cholesterol, triglycerides, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol were determined in 186 patients with essential hypertension (75 males, 111 females). Homeostasis model assessment was applied to assess the status of insulin resistance (HOMA-IR). RESULTS: Based on the HOMA-IR, the essential hypertension patients were divided into insulin-sensitive individuals (IS) and insulin resistant subjects (IR). The serum sE-selectin concentration was significantly higher in male group [(50.1?17.8)?g/L] than in female group [(40.6?16.6)?g/L] (P

ObjectiveTo study the effect of 8 Hz infrasound on the expression of 5-hydroxytryptamine (5-HT) in rats' hippocampus and temporal cortex.Methods140 male SD rats were randomly divided into the control group, and experimental groups that exposed to infrasound of 8Hz,90dB,100dB and 130dB for 1,7,14,21,28,35,42 days. Experimental groups were exposed to infrasound for 2 hours each day. The control group was only placed in the infrasonic storehouse but without infrasound. Rats' brains were taken as soon as the exposure finished and strained by immunohistochemistry. The content of 5-HT in hippocampus and temporal cortex was detected under an optical microscope.ResultsInfrasound groups had less expression of 5-HT in hippocampus and temporal cortex than the control group (P<0.01), and the least were at the 28th day for 90 dB and 100 dB groups and the 21st day for 130 dB group. Then the expression of 5-HT had an increase in each group.ConclusionThe deceased expression of 5-HT in rats' hippocampus and temporal cortex could result from infrasound of 8 Hz. Rules of change are related to the parameter of infrasound and the 130 dB 8 Hz infrasound can induce greater changes compared with that of 100 dB and 90 dB.

OBJECTIVE: To investigate the distribution of positive allergens in patients with allergic rhinitis in Changzhou. METHOD: A total of 4242 cases with allergic symptoms and signs underwent skin prick test with 16 kinds of standardized allergens. The common allergens were found out. The samples were stratified on seven age groups to analysis the distributive characteristics of allergens responsible for each group. The samples were also stratified on children group and adults group to analysis their response degree to dust mite. RESULT: 2638 cases (62.19%) had the positive reaction, including male 1380 (52.3%) cases, female 1258 (47.7%) cases. Dermatophagoides farinae and dermatophagoides pteronyssinus had the highest positive ratio (85.86%, 83.55%) in inhalation group, followed cockroach (11.49%) and Humulus L. (9.82%), fungus (2.92%) in the lower positive ratio. Shrimp (5.76%) was the most common allergen in food group. The distribution of common allergens in different age groups was variable. There was significantly higher sensitivity to dust mite between children group compared to adults group (P < 0.01). CONCLUSION The study shows that Dust mite was the mostly responsible common allergen in Changzhou district. The distribution of common allergens in children group and adults group was variable.
Adolescent ; Adult ; Aged ; Allergens ; analysis ; Animals ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Mites ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; diagnosis ; epidemiology ; Skin Tests ; Young Adult

Objective:To investigate the frequency and severity of systemic reactions (SRs) to standardized house dust mite subcutaneous immunotherapy (SCIT) in patients with perennial allergic rhinitis (AR), and to analyze the clinical risk factors.Methods:The clinical data of 362 patients including 209 males and 153 females, aged from 5 to 55 years old receiving SCIT at the Department of Otorhinolaryngology, the Third People′s Hospital of Changzhou were collected from May 2014 to July 2017. The SRs were classified as early-onset and delayed-onset, and 4 grades (grade Ⅰ to Ⅳ) to assess severity. The records of SRs were retrospectively analyzed, including the numbers/frequencies, symptoms and signs, onset of reaction and treatment. And the relationships between SRs and patient′s age, gender, allergen injection dose, accompanied allergic diseases were explored. All the statistical analyses were conducted using SPSS 19.0.Results:There were 57 cases (15.75%) of SRs in 362 patients. All the patients received a total of 12 308 injections and 111 SRs (0.90%) were observed. Among them, 31 (27.93%) were early-onset reactions and 80 (72.07%) were delayed-onset reactions; most of the SRs were grade Ⅰ reactions ( n=83, 74.78%), followed by grade Ⅱ ( n=25, 22.52%), grade Ⅲ ( n=3, 2.70%), and no fatal reactions occurred. The incidence of SRs in patients>14 years old was higher than that in patients ≤14 years old according to the number of cases and injections (35.14% vs 13.54%, 2.34% vs 0.76%, χ 2 value was 11.679, 28.162, respectively, all P<0.05), but no significant differences of SRs were observed in gender (18.66% vs 11.76%, 5.98% vs 5.62%, χ 2 value was 3.166, 0.095, respectively, all P>0.05). Fifteen SRs (13.51%) occurred during the build-up phase and 96 (86.49%) during the maintenance phases. SRs could occur in lots of dose phases, and 95 (85.59%) were distributed at high concentrations more than 40 000 SQ-U. The incidence of SRs in patients with multiple allergic diseases was significantly higher than that in patients with AR alone, with asthma or atopic dermatitis (30.67% vs 11.85%, χ 2=15.875, P<0.001). Meanwhile, the incidence of SRs in patients with pure AR was also significantly lower than that in patients with other allergic diseases (5.26% vs 20.56%, χ 2=13.783, P<0.001). Conclusions:The incidence of SRs is less than 1% according to the injection times, the severity of SRs is mostly slight, and the safety and tolerance are good during standardized house dust mite SCIT in perennial AR patients. Delayed-onset SRs are more common. The incidence of SRs is significantly correlated with age, high dose of allergen vaccine injection, and concomitant other allergic diseases (asthma, atopic dermatitis, etc).

Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.