Hereditary angioedema (HAE) is a rare but serious condition characterized by unpredictable and recurrent attacks affecting the skin and mucosa. HAE has wide-ranging impacts on the health-related quality of life (HRQoL) of patients. This study aims to assess the HRQoL of Chinese patients with HAE using the 36-item Short Form Health Survey (SF-36v2) and to explore potential risk factors for low HRQoL. A total of 104 patients (47 male and 57 female) over age 18 living in China with a known diagnosis of HAE due to C1-INH deficiency completed the SF-36v2 (generic HRQoL questionnaire). The results were compared to Chinese population norms. Subgroup analysis and logistic regression were used to interpret the data. SF-36v2 showed a significant reduction in all dimensions of HRQoL (p < 0.001) in patients with HAE compared with the general Chinese population. Female patients reported significantly lower bodily pain (BP) (p = 0.039) and physical component scores (PCSs) (p = 0.027) than male patients. Patients with mucosal edema tended to report lower role-physical (RP) limitations (p = 0.031) than patients with only skin edema. There were no differences between the mean scores of the SF-36 in relation to disease subtype, age, disease severity and long-term prophylaxis. Among female patients on long-term prophylaxis, social functioning (SF) (r = − 0.404, p = 0.010), role-emotional (RE) (r = − 0.320, p = 0.044) and mental component scores (MCSs) (r = − 0.313, p = 0.049) were negatively correlated with danazol dosage. A correlation between decreased disease control and decreased HRQoL scores was found, although the correlation was not significant in terms of RE or mental health (MH) scores. The logistic regression model revealed uncontrolled disease to be a risk factor for a low PCS (odds ratio 10.77, 95% confidence interval [CI] 1.78–65.06; p = 0.010) and laryngeal edema to be a risk factor for a low MCS (odds ratio 4.75, 95% CI 1.09–20.69; p = 0.038). Chinese HAE patients reported significantly lower HRQoL scores than the general population. Unsatisfactory disease control is a risk factor for decreased PCSs. Laryngeal edema is a risk factor for decreased MCSs.

Polycyclic aromatic hydrocarbons (PAHs) are considered to be endocrine disruptors. In this study, the evidence on the association between PAHs and diabetes was systematically reviewed. PubMed, EMBASE, and ISI Web of Science were systematically searched for studies reporting the association between PAHs and diabetes. Of the 698 articles identified through the search, nine cross-sectional studies were included. Seven were conducted in the general population and two in coke oven workers. Fixed-effects and random-effects models were used to calculate the total effect. Subgroup analysis was further carried out according to the types of PAH metabolites. The results showed that the odds of diabetes were significantly higher for the highest category of urinary naphthalene (NAP), fluorine (FLU), phenanthrene (PHEN), and total mono-hydroxylated (OH-PAH) metabolites compared to the lowest category. The pooled odds ratios (OR) and 95% confidence intervals (CI) were 1.52 (95%CI: 1.19, 1.94), 1.53 (95%CI: 1.36, 1.71), 1.43 (95%CI: 1.28, 1.60), and 1.49 (95%CI: 1.07, 2.08), respectively. In coke oven workers, 4-hydroxyphenanthrene (4-OHPh) was significantly correlated with an increased risk of diabetes. Exposure measurements, outcome definitions, and adjustment for confounders were heterogeneous between studies. The results of the current study demonstrate a potentially adverse effect of PAHs on diabetes. Further mechanistic studies and longitudinal studies are needed to confirm whether PAH metabolite levels are causative, and hence associative, with increased diabetes incidences.

Objective. Visceral adipose tissue (VAT) plays a central role in the balance of energy metabolism. The objective of this study was to investigate the differentially expressed proteins in VAT between morbidly obese (BMI >35 kg/m²) and normal weight Chinese women. Method. Nine morbidly obese women and 8 normal weight women as controls were enrolled. Abdominal VAT was excised and analyzed by label-free one-dimensional liquid chromatography tandem mass spectrometry (1D-LC-MS/MS). Differentially expressed VAT proteins were further analyzed with Gene Ontology (GO) analysis and Ingenuity Pathway Analysis (IPA). Masson’s trichrome staining and CD68 immunohistochemical staining of VAT were conducted in all subjects. Result. A total of 124 differentially expressed proteins were found with a ≥2-fold difference. Forty-one proteins were upregulated, and 83 proteins were downregulated in obese individuals. These altered VAT proteins were involved in the attenuation of the liver X receptor/retinoid X receptor (LXR/RXR) signaling pathway and the activation of the acute-phase response process. Three proteins (ACSL1, HADH, and UCHL1) were validated by western blotting using the same set of VAT samples from 6 morbidly obese and 7 normal weight patients, and the results indicated that the magnitude and direction of the protein changes were in accordance with the proteomic analysis. Masson’s trichrome staining and CD68 immunohistochemical staining demonstrated that there was much more collagen fiber deposition and CD68-positive macrophages in the VAT of morbidly obese patients, suggesting extensive fiber deposition and macrophage infiltration. Conclusion. A number of differentially expressed proteins were identified in VAT between morbidly obese and normal weight Chinese females. These differential proteins could be potential candidates in addressing the role of VAT in the development of obesity.

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease with heterogeneous clinical symptoms. The metabolomic profile of HAE remains unknown. Uncovering the metabolic signatures of HAE may provide inspiration for a comprehensive understanding of HAE pathogenesis and may help explore potential new metabolic biomarkers. We performed a comprehensive metabolic analysis using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). Urine samples from 34 HAE patients and 82 healthy controls (HCs) were collected to characterize the metabolic signatures associated with HAE. The metabolomes of HAE patients carrying different mutation types were also compared. A total of 795 metabolites were accurately detected and quantified. We considered 73 metabolites as differential metabolites in HAE patients (with an importance in projection (VIP) value > 1.0, q-value < 0.05, and fold change (FC) ≥ 1.2 or FC ≤ 0.8). Several metabolites associated with riboflavin metabolism, the citrate cycle, oxidative stress, and inflammation, including xanthine, oxypurinol, vitamin B2, and isocitrate, were significantly altered in HAE patients. No significantly different metabolites were found in HAE patients carrying different mutation types. The present study highlights that metabolic disturbances in the purine metabolism, riboflavin metabolism, and TCA cycle may be involved in the pathogenesis of HAE. Although biochemical significance requires further experimental verification, these findings may help to identify novel candidate metabolite biomarkers associated with HAE.

Background: Hereditary angioedema (HAE) is a rare disease with heterogeneous clinical symptoms. It is vitally important to predict whether an HAE patient will develop severe symptoms in clinical practice, but there are currently no predictive biomarkers for HAE stratification. Plasma N‐glycomes are disease‐specific and have great potential for the discovery of non‐invasive biomarkers. In this study, we profiled the plasma N‐glycome of HAE patients from two independent cohorts to identify candidate biomarkers.Methods: Linkage‐specific sialylation derivatization combined with matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry detection and automated data processing was employed to analyze the plasma N‐glycome of two independent type‐1 HAE cohorts.Results: HAE patients had abnormal glycan complexity, galactosylation, and α2,3‐ and α2,6‐linked sialylation compared to healthy controls (HC). The classification models based on dysregulated glycan traits could successfully discriminate between HAE and HC with area under the curves (AUCs) being greater than 0.9. Some of the aberrant glycans showed response to therapy. Moreover, we identified a series of glycan traits with strong associations with the occurrence of laryngeal or gastrointestinal angioedema or disease severity score. Predictive models based on these traits could be used to predict disease severity (AUC > 0.9). These results were replicated in an independent cohort.Conclusions: We reported the full plasma N‐glycomic signature of HAE for the first time, and identified potential biomarkers. These findings may play a critical role in predicting disease severity and guide the treatment of HAE in clinical practice. Further protein‐specific and prospective studies are needed to validate our findings.

Hereditary angioedema (HAE) is a rare disease characterized by recurrent episodes of cutaneous and submucosal edema. The clinical course of HAE is heterogeneous and unpredictable. There are no reliable indicators associated with angioedema attacks and severity. Throat microbiota plays vital roles in the maintenance of human health, while its association with HAE is barely understood. Therefore, this study aimed to investigate the alteration of throat microbiota and its correlation with attacks severity in HAE patients. Throat swab samples were collected from HAE patients and their healthy family members, and then subjected to 16S rRNA sequencing. Alpha and beta diversity were used to examine the diversity and structure of bacterial communities. The relative abundance of individual bacteria was compared between study groups to determine the discriminant taxa. Spearman's correlation and linear regression were applied to analyze the correlation between throat bacteria and attacks severity. Irrespective of the study groups, the throat microbiome was predominantly occupied by Firmicutes, Bacteroidetes, Proteobacteria, and Fusobacteria. The recent onset of laryngeal edema is associated with the altered composition of microbiome community in HAE patients. The relative abundance of Bacteroidetes and Prevotellaceae was significantly increased in patients with recent episodes of laryngeal edema, compared to patients without recent episodes of laryngeal edema. Additionally, HAE attack severity scores positively correlated with the relative abundance of Bacteroidetes. We reported alterations of the throat microbial communities in HAE patients and explored the correlation between bacteria and edema severity, which may shed light on understanding the disease course and developing new therapeutic strategies for HAE.