PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.
Allergens ; Analgesics ; Animals ; Antipyretics ; Asian Continental Ancestry Group ; Asthma ; Bronchial Hyperreactivity ; Cats ; Child ; Classification ; Cohort Studies ; Comorbidity ; Dermatophagoides pteronyssinus ; Disease Management ; Humans ; Methacholine Chloride ; Odds Ratio ; Ownership ; Parturition ; Phenotype ; Prevalence ; Rhinitis, Allergic ; Risk Factors ; Skin

Objective To explore the associations of body mass index (BMI), waist circumference (WC), waist height ratio (WHtR) and the prevalence of hypertension in elderly residents over 60 years in Baodi district, Tianjin. Methods Residents over 60 who underwent medical examinations in the Koudong Health Center, Baodi district, Tianjin, were all invited to participate in the study from April to May, 2018. Participants were asked to fill out structured questionnaires and undergo physical examinations. Stratified analysis and logistic regression analysis were applied to examine joint effects and interactions of BMI and WC (or WHtR) on the risk of hypertension. Results A total of 1 417 residents (83.75%) out of 1 692 residents participated in the study. The prevalence of hypertension in the participants was 46.36%. 66.50% of the participants were BMI overweight or obese. Participants with central obesity accounted for 74.66% (measured by the WC) and 75.38% (by the WHtR). Compared to the normal weight measured by the BMI or the WC, BMI overweight (OR=1.65, 95%CI: 1.19-2.30) or obesity (OR=3.41, 95%CI: 2.23-5.20) and WC central obesity (OR: 1.49, 95%CI: 1.00-2.23) were associated with increased risk of hypertension. The joint effects of BMI and WC (OR=2.49, 95%CI: 1.78-3.46), or BMI and WHtR (WHtR overweight: OR=2.05, 95%CI: 1.41-2.99; WHtR obesity: OR=2.37, 95%CI: 1.50-3.76) were greater than the single effect of the latter (WC overweight/obesity: OR=1.39, 95%CI: 0.90-2.15; WHtR overweight: OR=1.02, 95%CI: 0.62-1.66; WHtR obesity: OR=1.44, 95%CI：0.55-3.81). Conclusions Of the three indices, BMI is strongly correlated with the risk of hypertension. BMI overweight or obesity has enhanced the association of WC or WHtR and the risk of hypertension, suggesting that weight control in the normal range, especially measured by the BMI index, may prevent and control hypertension.

The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain ; Haplorhini ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Inflammation ; Macaca mulatta ; Magnetic Resonance Imaging ; Microglia ; Middle Cerebral Artery ; Primates ; Stroke ; Transforming Growth Factor beta

No abstract available.
Dyslipidemias ; Korea

N-methyladenosine (mA), catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14, is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However, the roles and precise mechanisms of mA modification in regulating neuronal development and adult neurogenesis remain unclear. Here, we examined the function of Mettl3, the key component of the complex, in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced mA levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neuronal development and skewed the differentiation of aNSCs more toward glial lineage, but also affected the morphological maturation of newborn neurons in the adult brain. mA immunoprecipitation combined with deep sequencing (MeRIP-seq) revealed that mA was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, mA was present on the transcripts of histone methyltransferase Ezh2, and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated mA modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.
Adenosine ; analogs & derivatives ; metabolism ; Adult Stem Cells ; cytology ; metabolism ; Animals ; Brain ; metabolism ; Cell Differentiation ; genetics ; Cell Proliferation ; Enhancer of Zeste Homolog 2 Protein ; metabolism ; Gene Expression Regulation ; Methyltransferases ; metabolism ; Mice, Inbred C57BL ; Neural Stem Cells ; cytology ; metabolism ; Neurogenesis ; genetics ; Neurons ; cytology ; metabolism ; RNA, Messenger ; genetics ; metabolism

Objective To compare the changes of safe sexual behavior and its intention among college students in Beijing between 2006 and 2016, and to provide evidence for reproductive health education for prevention and control of sexually transmitted diseases (STDs). Methods By a stratified random sampling method,a questionnaire survey was conducted among college students in Beijing in 2006 and 2016 respectively. Results The rate of sexual behaviors declined ( 2=81.150,P<0.001), while the percentage of homosexual behavior among respondents in 2016 was higher than that in 2006( 2=12.115,P<0.001). Meanwhile, the age of first sexual intercourse (t=12.009, P<0.001) and the intention of safe sexual behavior declined( 2=10.375,P<0.001). In both surveys, the proportion of risk behaviors among students who ever had sexual behavior was higher than that of students never had sexual behavior. Multivariate linear regression analysis showed that the intention of safe sexual behavior among college students was associated with gender, age, self-efficacy of condom use, UNGASS index, visiting entertainment places and browsing pornographic information on the Internet(all P<0.05).Conclusions Compared with 2006, the safe sexualbehavior, intention and their risk factors among college students in Beijing changed greatly in 2016. The contents and approaches of intervention related to STDs and reproductive health should be changed according to the current situation in order to improve the intention of safe sexual behavior among college students and to control the occurrence of STDs.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

BACKGROUND: Basal metabolic rate (BMR) is an important indicator of human energy metabolism, and low BMR leads to the dysfunction of liver and kidney. Low BMR is usually found in patients with hip fractures, but there is a lack of study on the relationship between mortality of hip fracture and low BMR. OBJECTIVE: To investigate the effect of low BMR on the 1-year mortality in older adults with hip fractures. METHODS: Totally 507 patients with hip fractures aged more than 60 years from January 2014 to March 2016 were included in this retrospective study. Age, sex, surgery or not, surgical pathway, duration from injury to surgery, hospitalized pulmonary infection, number and kind of comorbidities, and 1-year mortality were recorded. BMR on admission was recorded, and multiple Logistic regression analysis was applied. RESULTS AND CONCLUSION: All patients were followed up for 13-15 months, and the 1-year mortality was 13.41% (68/507). The mortality in the low BMR group was significantly higher than that in the non-low BMR group (P ＜ 0.05). Logistic regression analysis showed that older age, conventional treatment, number of combined medical diseases, hospitalized pulmonary infection, and low BMR are risk factors for 1-year mortality in older adults with hip fracture. These results imply that low BMR is strongly associated with 1-year mortality in older adults with hip fracture. BMR can reflect the nutritional status, neuroendocrine, cellular and energy metabolism. Thereafter, for older adults with hip fractures and low BMI, nutrition therapy, re-warming, and endocrine therapy may help reduce the trauma-induced mortality.

AIM:To study the effect of microRNA (miR)-24 on chemotherapy sensitivity and its possible mechanisms in human lung adenocarcinoma A549 cells. METHODS:The expression of miR-24 in the A549 cells and A549/DDP cells was determined by real-time PCR. Transfection of miR-24 inhibitor was used to down-regulate the miR-24 level in the A549/DDP cells. The viability and apoptosis rate were measured by CCK-8 assay and flow cytometry, respec-tively. The protein levels of Bcl-2, Bax, cleaved caspase-3, cleaved caspase-9, cytochrome C (Cyt C), phosphorylated extracellular signal regulated kinase (p-ERK) and P53 were detected by Western blot. Luciferase reporter assay was used to predict and identify the target genes of miR-24. RESULTS:The expression of miR-24 was significantly higher in the A549/DDP cells than that in the A549 cells (P<0.05). miR-24 inhibitor induced cell apoptosis and increased the sensi-tivity of the A549/DDP cells to cisplatin. Furthermore, miR-24 inhibitor down-regulated the ratio of Bcl-2/Bax, while up-regulated the protein levels of P53, p-ERK, cleaved caspase-9, cleaved caspase-3 and Cyt C. Incubation with U0126, a specific ERK inhibitor, partly reversed the viability of miR-24 inhibitor transfected A549/DDP cells. Bioinformatics analy-sis demonstrated that p53 was a potential target gene of miR-24. Co-teansfection of miR-24 inhibitor and P53 siRNA in A549/DDP cells partially reversed the effect of miR-24 inhibitor on cell viabiltiy. CONCLUSION:Down-regulation of miR-24 increases the sensitivity of A549/DDP cells to cisplatin. The mechanism may be related to directly targeting p53 gene and over-activation of ERK/P53 signaling pathway, thus promoting apoptosis via mitochondrial apoptosis pathway.

Objective To study the therapeutic effects of arthroscopic debridement combined with sodium hyaluronate injection in treatment of Kashin-Beck disease with ankle arthritis.Methods Using prospective study,Kashin-Beck disease patients with ankle arthritis,who had underwent arthroscopic debridement combined with sodium hyaluronate injection,were selected as study subjects.X-ray stratification was performed based on Kellgren-Lawrence grading method,grade 1,2,3 were studied,if there were fewer patients at grade 1,then merge with grade 2.Visual analogue scale (VAS),anterior and posterior ankle activity and ankle hindfoot score were used to evaluate the effects before and 3,6,12 months after the treatment.Results Totally 33 patients were collected,VAS scores (6.9 ± 0.2,2.9 ± 0.2,2.1 ± 0.1,1.9 ± 0.1),anterior and posterior ankle activities (20.9 ± 0.6,31.5 ± 0.6,32.1 ± 0.6,34.1 ± 0.4),and ankle hindfoot scores (51.3 ± 0.5,70.8 ± 1.1,76.0 ± 0.9,77.0 ± 0.9) before and 3,6,12 months after the treatment,were compared,and the differences were statistically significant (F =267.47,703.09,756.49,P ＜ 0.01).VAS scores (7.0 ± 0.2,2.8 ± 0.2,1.7 ± 0.1,1.7 ± 0.1;7.0 ± 0.3,3.2 ± 0.3,2.8 ± 0.2,2.2 ± 0.2),anterior and posterior ankle activities (22.4 ± 0.7,32.5 ± 0.6,33.1 ± 0.6,51.3 ± 0.5;18.1 ± 0.9,29.6 ± 1.0,30.2 ± 1.0,31.4 ± 0.9),and ankle hindfoot scores (51.6 ± 0.9,70.9 ± 0.5,77.7 ± 0.9,79.1 ± 1.0;50.6 ± 0.5,65.5 ± 1.8,72.8 ± 1.4,72.9 ± 1.4) in grade 1 + grade 2,and grade 3 patients before and 3,6,12 months after the treatment,were compared,and the differences were statistically significant (F =244.80,64.04;379.94,498.83;1 393.07,159.70,P ＜ 0.01).Compared with those before the treatment,VAS scores of all,grade 1 + grade 2,and grade 3 patients in 3,6,12 months after the treatment significantly decreased,anterior and posterior ankle activities and ankle hindfoot scores significantly increased (P ＜ 0.05).Conclusion Arthroscopic debridement combined with sodium hyaluronate injection is effective in the treatment of Kashin-Beck with disease ankle arthritis.