Although the prevalence of allergic diseases has been rising in China since the late twentieth century, comprehensive nationwide epidemiological data covering all age groups and multiple allergic conditions remain scarce. To investigate the epidemiological patterns of eight major allergic diseases in China, including their national and regional prevalence, demographic distribution, and comorbidity profiles, the National Epidemiology Study of Asthma and Allergies in China (NESAAC) was a nationwide cross-sectional survey conducted from September 2010 to December 2015. A multistage stratified cluster sampling method was employed across seven geographical regions, covering 882 communities and 587 villages in 16 cities. Data were collected via face-to-face interviews using standardized questionnaires. Prevalence was calculated for three categories: lifetime symptoms, current symptoms (past 12 months), and physician-diagnosed history. Among the 121,023 participants analyzed, the current symptom prevalence of each specific disease was: allergic rhinitis (4.2%), asthma (0.9%), eczema (0.7%), drug allergy (0.6%), food allergy (0.4%), urticaria (0.4%), contact dermatitis (0.3%), and anaphylactic shock (0.02%). Geographic variations were notable, with the highest prevalence consistently observed in North, East, and South China. Urban residents had significantly higher prevalence than rural residents across all conditions except anaphylactic shock. Age distribution revealed eczema and food allergy predominance in children under 6 years, whereas asthma and drug allergy prevalence increased with age. Most conditions were more prevalent among females than males. Allergic rhinitis was not only the most common condition but also demonstrated the strongest comorbidity, particularly with asthma. This first nationwide, all-age survey underscores marked epidemiological variations in allergic diseases across China.

Background::Atopic dermatitis (AD) is a chronic inflammatory skin disorder impacting populations worldwide, although its clinical characteristics and patient demographics remain uncharacterized in China. The aim of this study was to investigate the demographics, comorbidities, aggravating factors, and treatments in AD patients across different age groups in China.Methods::This cross-sectional study included Chinese AD patients from 205 hospitals spanning 30 provinces. Patients completed dermatologist-led surveys of general medical history, comorbidities, AD-related aggravating factors, and medications. Two-level mixed-ordered logistic regression was used to evaluate aggravating factors.Results::Overall, 16,838 respondents were included in the final analysis (aged 30.9 ± 24.1 years). The proportion of severe AD was the highest in patients with AD onset at ≥60 years (26.73%). Allergic rhinitis and hypertension were the most common atopic and metabolism-related non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergies, and diabetes. Aggravating factors including foods, seasonal changes, and psychological factors were also linked to AD severity. The cross-sectional survey implied that severe AD may be related to the undertreatment of effective systemic or topical interventions.Conclusion::To enhance the management of AD, it is crucial to consider both aggravating factors and the increased utilization of systemic immunotherapy.Registration::ClinicalTrials.gov, NCT05316805

To the Editor: Chronic urticaria, prevalent globally and increasing in China, predominantly affects young and middle-aged women, impacting their quality of life (QoL).[1] Standard treatment involves second-generation H1 antihistamines, with bilastine showing promise due to its selective action and minimal side effects. However, direct comparative studies are scarce, particularly in the Chinese population. We aimed to evaluate the efficacy and safety of bilastine compared to levocetirizine in Chinese patients. This multicenter, double-blind, double-dummy, non-inferiority, phase III trial conducted at 18 centers (CTR20181967, www.chinadrugtrials.org.cn; ChiCTR2300072867, www.chictr.org.cn) was approved by the Medical Ethics Committee of Peking University People's Hospital (No. 2018PHA062-002) [Supplementary Table 1, https://links.lww.com/CM9/B953]. All patients provided written informed consent. Participants with chronic idiopathic urticaria who met the eligible criteria [Supplementary Table 2, https://links.lww.com/CM9/B953] were randomized to 1:1 to 28-day treatment with bilastine 20 mg or levocetirizine 5 mg daily, alongside matching placebos, using a centralized system to ensure blinding. The primary endpoint was the Total Symptom Score (TSS) for itching, wheals number, and size. Secondary endpoints encompassed detailed TSS analysis, Urticaria Composite Score (UCS), Dermatology Life Quality Index (DLQI), Visual Analog Scale (VAS), and Global Clinical Impression (GCI). Safety was continuously monitored through adverse events (AEs) follow-up. Assuming an 80% power, one-side alpha of 0.025, a standard deviation of 2.16, a non-inferior margin of 0.8, and a 20% dropout rate, it was planned to randomize 288 participants (bilastine:levocetirizine = 144:144). The primary endpoint analysis of non-inferiority was assessed on the Per-Protocol Population (PP) set and the secondary efficacy analyses were performed in the modified intent-to-treat (mITT) population. In this study, 288 patients were randomized across two groups (144 each) [Supplementary Figure 1, https://links.lww.com/CM9/B953]. In the mITT population, mean ages were 35.5 ± 10.8 years and 36.5 ± 12.1 years in the bilastine and levocetirizine groups, respectively, with male representation at 49.6% and 37.1%. Baseline characteristics showed no significant differences between groups [Supplementary Table 3, https://links.lww.com/CM9/B953]. In the primary endpoint analysis of the PP set (bilastine: 122, levocetirizine: 120), baseline TSS for reflective symptoms were 4.06 ± 2.04 (bilastine) and 4.43 ± 2.10 (levocetirizine). By day 28, these scores reduced to 1.53 ± 1.91 and 1.37 ± 1.88, respectively [Table 1]. The mean changes from baseline in TSS (reflective) were –2.54 ± 2.59 (bilastine) and –3.06 ± 2.47 (levocetirizine), with least squares (LS) mean difference of 0.17 (–0.19, 0.54), demonstrating non-inferiority [Supplementary Figure 2, https://links.lww.com/CM9/B953]. Superiority was not established in exploratory analysis. Daytime and nighttime scores for itching intensity, wheals number, and maximum wheal size decreased in both groups, with no significant differences in changes between groups (P >0.05 for all). The areas under the TSS score curves were 44.09 ± 43.35 (bilastine) and 41.44 ± 41.55 (levocetirizine), not significantly different (P = 0.604). Participant-assessed TSS (instantaneous) decreased from baseline to day 28 (bilastine: 3.19 ± 2.70 to 1.34 ± 1.87; levocetirizine: 3.20 ± 2.75 to 1.06 ± 1.77), with no significant intergroup differences in changes (–2.13 ± 2.94 vs. –2.04 ± 2.68, P = 0.829). Investigator-assessed TSS (instantaneous) also showed comparable decreases in both groups by day 28 (–2.12 ± 2.76 bilastine, –2.29 ± 2.93 levocetirizine; P = 0.861) [Table 1]. Table 1 - Efficacy endpoints of bilastine compared to levocetirizine in Chinese patients. Items Bilastine 20 mg Levocetirizine 5 mg Difference, LS means (95% CI) P-value Primary endpoint, n 122 120 TSS (reflective) Day 28 1.53 ± 1.91 1.37 ± 1.88 Change from baseline –2.54 ± 2.59 –3.06 ± 2.47 0.17 (–0.19, 0.54) 0.356* Secondary endpoint, n 139 140 TSS domain Itching intensity, daytime, LS mean (95% CI) –0.81 (–0.89, –0.73) –0.88 (–0.96, –0.79) 0.07 (–0.05, 0.18) 0.2525 Itching intensity, nighttime, LS mean (95% CI) –1.0 (–1.08, –0.92) –1.07 (–1.15, –0.99) 0.07 (–0.05, 0.18) 0.2393 Wheals number, daytime, LS mean (95% CI) –0.67 (–0.76, –0.58) –0.75 (–0.84, –0.66) 0.08 (–0.05, 0.21) 0.2033 Wheals number, nighttime, LS mean (95% CI) –0.83 (–0.92, –0.74) –0.87 (–0.96, –0.79) 0.05 (–0.08, 0.17) 0.4773 Maximum size of wheals, daytime, LS mean (95% CI) –0.84 (–0.94, –0.74) –0.88 (–0.98, –0.78) 0.04 (–0.11, 0.18) 0.6239 Maximum size of wheals, nighttime, LS mean (95% CI) –1.03 (–1.14, –0.92) –1.02 (–1.13, –0.91) –0.01 (–0.16, 0.14) 0.9039 UCS (reflective) Day 28 0.98 ± 1.22 0.87 ± 1.19 Change from baseline –1.62 ± 1.63 –2.05 ± 1.59 0.171 Participant-assessed TSS (instantaneous) Day 28 1.34 ± 1.87 1.06 ± 1.77 Change from baseline –2.13 ± 2.94 –2.04 ± 2.68 0.829 Investigator-assessed TSS (instantaneous) Day 28 1.35 ± 1.83 1.30 ± 2.09 Change from baseline –2.12 ± 2.76 –2.29 ± 2.93 0.861 Participant-assessed UCS (instantaneous) Day 28 0.9 ± 1.2 0.6 ± 1.1 Change from baseline –1.3 ± 1.9 –1.4 ± 1.7 0.127 Investigator-assessed USC (instantaneous) Day 28 0.9 ± 1.2 0.8 ± 1.2 Change from baseline –1.3 ± 1.8 –1.5 ± 1.8 0.522 Investigator's GCI, n (%) Marked improvement 71 (51.1) 71 (50.7) 0.420 Moderate marked improvement 41 (29.5) 48 (34.3) 0.964 Minimal slight improvement 20 (14.4) 13 (9.3) 0.805 No change or worse 1 4 Not evaluated 6 4 QoL Day 28, mean ± SD 4.1 ± 4.6 3.7 ± 4.3 Change from baseline, mean ± SD –6.1 ± 5.1 –7.2 ± 5.8 0.209 Sleep quality impacted by chronic idiopathic urticarial, n (%) 0.707 Not at all 80 (57.6) 89 (63.6) Somewhat 43 (30.9) 37 (26.4) Moderately 7 (5.0) 8 (5.7) A lot 2 (1.4) 1 (0.7) Very much 1 (0.7) 0 *Non-inferiority test. Data were shown as mean ± SD, except when indicated otherwise. CI: Confidence interval; GCI: Global clinical impression; LS: Least square; QoL: Quality of life; SD: Standard deviation; TSS: Total Symptom Score; UCS: Urticaria Composite Score. Regarding secondary endpoints, baseline UCS (reflective) scores were 2.59 ± 1.28 (bilastine) and 2.90 ± 1.37 (levocetirizine), decreasing to 0.98 ± 1.22 and 0.87 ± 1.19, respectively, on day 28. Changes in UCS (reflective) were not significantly different (–1.62 ± 1.63 vs. –2.05 ± 1.59, P = 0.171). Both participant-assessed and investigator-assessed UCS (instantaneous) scores decreased similarly by day 28, with no significant difference in changes (participant-assessed: –1.3 ± 1.9 vs. −1.4 ± 1.7, P = 0.127; investigator-assessed: –1.3 ± 1.8 vs. –1.5 ± 1.8, P = 0.522). The investigator's GCI showed similar proportions of marked improvements (51.1% vs. 50.7%, P = 0.420) and moderate to minimal improvements (P >0.05) between groups. The DLQI scores on day 28 were 4.1 ± 4.6 and 3.7 ± 4.3, indicating comparable QoL improvements (–6.1 ± 5.1 vs. –7.2 ± 5.8, P = 0.209). The mean VAS scores for discomfort decreased significantly in both groups (bilastine: 58.50 ± 22.13–20.53 ± 20.72; levocetirizine: 61.68 ± 23.21–16.55 ± 20.55), with no significant differences on days 14 and 28 (P >0.05). The proportions of patients unaffected in sleep by chronic idiopathic urticaria increased similarly post-treatment (P >0.05) [Table 1]. In this study, exposure duration averaged 26.7 ± 3.8 days (bilastine) and 26.1 ± 5.1 days (levocetirizine). Treatment-emergent AEs (TEAEs) were reported in 30.2% (bilastine) and 34.0% (levocetirizine) of participants, with no dose adjustments or treatment interruptions due to TEAEs. Treatment discontinuations due to TEAEs occurred in one bilastine participant (0.7%, anxiety) and two levocetirizine participants (1.4%, blurred vision; diarrhea and lethargy). Common TEAEs in ≥3% of either group included sinus arrhythmia, elevated blood triglycerides, electrocardiogram T wave abnormality, hyperuricemia, and somnolence [Supplementary Table 4, https://links.lww.com/CM9/B953]. No serious adverse events were reported, and all TEAEs were mild to moderate. Moderate TEAEs were observed in 3.6% of bilastine and 2.1% of levocetirizine participants. In this study, bilastine significantly alleviated symptoms of chronic idiopathic urticaria in Chinese patients. It also showed non-inferiority to levocetirizine, aligning with Western population studies[2] and meta-analyses.[3] Although superiority wasn't established, possibly due to primary endpoint selection and insufficient power for superiority analysis, bilastine stands as a strong first-line treatment candidate for Chinese patients with chronic idiopathic urticaria, despite potential regional variations in rescue medication use. Podder et al[4] reported notable improvements in QoL with both bilastine and levocetirizine, with bilastine showing fewer TEAEs of somnolence. This aligns with a meta-analysis underscoring bilastine's efficacy in symptom control and QoL enhancement.[5] Nevertheless, morning administration may lead to heightened somnolence in the levocetirizine group. This study demonstrated that bilastine significantly alleviated physical discomfort from chronic idiopathic urticaria, and might enhance participants' QoL and sleep. Bilastine's minimal sedation and negligible impact on tasks like driving may be due to its lower brain histamine H1 receptor occupancy,[6] suggesting it as a potentially preferred option for managing chronic idiopathic urticaria. This trial, while contributing valuable insights, has limitations. The 28-day treatment period does not fully represent the chronic nature of idiopathic urticaria where long-term treatment is common. The study also focused solely on the approved dose of bilastine, although higher dosing has been showed to be safe and effective. The use of different assessment tools also poses comparability challenges. Despite these constraints, bilastine demonstrated significant improvement in symptoms and QoL, with a safety profile comparable to levocetirizine, suggesting its efficacy for Chinese patients with chronic idiopathic urticaria. Further studies are needed to explore long-term treatment outcomes and dosing variations of bilastine. Acknowledgments This study was sponsored by Menarini China. The authors would like to thank Menarini for sponsoring this phase III study IQVIA for providing CRO services and MedSci for medical writing services. In addition, we would like to thank all the staff from 18 hospitals who participated in this study. Conflicts of interest None.

Background: Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin disorders that causes great disease burdens world-wide. The demographics and clinical characteristics of AD are different between countries, regions, and age groups yet these differences were not well characterized in China. To get well guidance for AD clinicians, we described the demographics, clinical characteristics, comorbidities, patient-identified aggravating factors and treatment of AD in all-age patients in China. Methods: This study included Chinese individuals diagnosed with AD by accredited clinicians in the department of dermatology of 205 hospitals from 31/34 provincial administrative divisions across China during August, 2021 to September, 2022. All included patients completed dermatologist-lead interviews regarding their general medical history, comorbidities, AD-related aggravating factors and medications. Two-level mixed ordered logistic regression was used to evaluate factors for aggravation of the disease. Results: Overall, 16838 respondents were included in the final analysis with a mean age of 30.94 years (standard deviation, ± 24.08 years). The proportion of patients with severe AD was the highest in patients with onset of AD at ≥60 years old (26.73%). Allergic rhinitis and hypertension were the most common atopic and non-atopic comorbidities, respectively. AD severity was significantly associated with chronic urticaria, food allergy and diabetes. There was a high proportion of severe AD in patients who had aggravating factors such as seafood, lamb and beef, chili peppers, alcohol, seasonal changes, and psychological factors. Cross-sectional survey revealed unmet needs of severe AD in treatment strategy, in lack of immunosuppressants’ and biological agents’ application. Conclusion: Treatment of comorbidities and control of aggravating factors significantly contribute to AD management. Improving systemic immunotherapy could reduce the incidence of severe AD.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by relapsed eczema and serious pruritus. High-mobility group box 1 protein (HMGB1) is a nuclear-binding protein and serves as an alarmin to promote inflammatory responses. Methods: In this study, we established an AD mouse model by topical use of MC903 on ears and then used a specific HMGB1-binding peptide cIY8 and a HMGB1 inhibitor of glycyrrhizin to investigate HMGB1 on fibroblast activation in the pathogenesis of AD-like symptoms. Results: Topical use of cIY8 and oral use of glycyrrhizin significantly improved the MC903-induced AD-like symptoms and pathological changes of the ears and scratching behavior in an AD mouse model; cIY8 treatment inhibited the higher mRNAs of IL-1α, IL-4, IL-5, IL-13, and IL-31 in the ears. In human fibroblasts, HMGB1 caused nuclear translocation of NF-kB, and the nuclear translocation could be inhibited by pre-treatment of HMGB1 with cIY8, suggesting that NF-κB signaling pathway participates in the HMGB1-induced inflammation of AD in fibroblasts and that cIY8 effectively impedes the function of HMGB1. Glycyrrhizin inhibited the Ca2+ signaling induced by ionomycin in mouse primary fibroblasts. The fibroblast-related proteins of α-SMA, Hsp47, and vimentin and the pruritus-related proteins of IL-33 and periostin were increased in the ears of the AD mouse model, the ratio of EdU incorporation became higher in mouse fibroblasts treated with MC903, and the higher proliferation and inflammatory responses of the fibroblasts could be reversed by glycyrrhizin treatment. Conclusions: Fibroblast activation by HMGB1 is one of the critical processes in the development of inflammation and pruritus in the AD mouse model. The specific HMGB1-binding peptide cIY8 and the HMGB1 inhibitor glycyrrhizin inactivate skin fibroblasts to alleviate the inflammation and pruritus in the AD mouse model. Peptide cIY8 may be topically used to treat AD patients in the future.

Introduction Atopic dermatitis (AD) exhibits difference in immune polarization between Caucasians and Asian races due to which an evaluation of the efficacy and safety of Pimecrolimus (PIM) in Asian population is called for. The current study addresses the need via a sub-group analysis of the PETITE study (NCT00120523) to evaluate the safety and efficacy of PIM in Chinese infants. Materials and methods Patients with AD (≥3 months–<12 months of age) were randomized in a 1:1 ratio to either PIM 1% cream or topical corticosteroids (TCS). The primary endpoint was safety. The secondary endpoint was efficacy. Results 120 patients were randomized to either PIM 1% or TCS (n = 61 for PIM, n = 59 for TCS). The most often reported adverse events were reported by similar proportions of patients treated with PIM or TCS. There was a progressive increase in overall IGA treatment success in infants treated with PIM (82.9%, p < .05, 95% CI: 70.4, 95.3) after 26 weeks which was comparable to the TCS group (88.5%, p < .05, 95% CI: 79.8, 97.1). Conclusion PIM showed an early and sustained efficacy in the Chinese sub-population with a substantial corticosteroid-sparing effect in patients with AD.

Chronic spontaneous urticaria (CSU) is characterized by the spontaneous development of wheals, itching, and/or angioedema, for ≥6 weeks. In China, non-sedating H1-antihistamines (H1AH) are the recommended first-line treatment, with escalation up to 4× the standard dose in symptomatic patients to achieve control. Treatment options for Chinese patients who remain symptomatic on H1AH treatment are limited. This 20-week randomized, double blind, placebo-controlled, parallel-group study investigated the efficacy and safety of omalizumab as an add-on therapy for the treatment of patients with CSU who remained symptomatic despite H1AH treatment in China. Adult patients (N = 418) diagnosed with refractory CSU for ≥6 months were randomized (2:2:1) to receive omalizumab 300 mg (OMA300), omalizumab 150 mg (OMA150) or placebo, subcutaneously, every 4 weeks. Primary outcome was change from baseline to week 12 in weekly itch severity score (ISS7). Safety was assessed by rates of adverse events (AEs). Demographic and disease characteristics at baseline were comparable across treatment groups. At week 12, statistically significant greater decreases from baseline were observed in ISS7 with OMA300 (least square mean difference [LSM]: -4.23; 95% confidence interval [CI]: -5.70, -2.77; p < 0.001) and OMA150 (LSM: -3.79; 95% CI: -5.24, -2.33; p < 0.001) versus placebo. Incidence of treatment-emergent AEs over 20 weeks was slightly higher with OMA300 (71.3%) compared to OMA150 and placebo groups (64.7% and 63.9%, respectively). The incidences of serious AEs were balanced between groups. This study demonstrated the efficacy and safety of omalizumab in Chinese adult patients with CSU who remained symptomatic despite H1AH therapy.

Atopic dermatitis (AD) is sometimes accompanied by alopecia areata (AA) or, in severe cases, alopecia universalis (AU). Preclinical studies have shown that type 1 and type 2 cytokines are involved in AD and AA.1,2 Janus kinase (JAK) inhibitors are effective blockers of JAK/signal transducer and activator of transcription-mediated inflammatory signaling pathways, which regulate multiple cytokines, such as interleukins and interferons.3 A recent case report showed hair regrowth after simultaneous treatment of AU and AD with tofacitinib, a selective inhibitor of JAK 1 and JAK 3.

肥大细胞长期定居在皮肤及黏膜中,是荨麻疹、食物过敏、哮喘、过敏性休克等变态反应疾病的主要效应细胞.肥大细胞参与的皮肤疾病大多表现为显著瘙痒.特异性IgE介导肥大细胞活化释放组胺进而引起神经敏化是瘙痒信号传递的经典神经免疫途径.近年来研究表明,除组胺外,肥大细胞释放其他炎症介质活化外周神经介导瘙痒信号传递也尤为重要.本文回顾肥大细胞在瘙痒发生中的生物学功能,以及神经免疫机制在常见瘙痒性皮肤疾病中的作用.同时综述靶向药物在瘙痒治疗中的进展.

目的 探讨中药单体人参皂甙Rg3对原代培养人喉鳞癌细胞上皮-间质转化的影响及SIX1和TGF-β在上皮-间质转化中的作用.方法 术中留存人喉鳞状细胞癌组织,常规处理后,体外进行人喉鳞癌原代细胞培养,待细胞传代稳定后分为对照组、顺铂组、Rg3组.顺铂组加入顺铂,使其终浓度为3μg/mL;Rg3组加入Rg3,使其终浓度为300μg/mL.处理后继续培养细胞24 h,免疫组化及Western blot检测3组细胞中SIX1、TGF-β及上皮标志物E-cadherin蛋白表达情况,RT-PCR法检测各组原代细胞中SIX1 mRNA、TGF-βmRNA及E-cadherin mRNA表达情况.结果 免疫组化染色显示对照组SIX1、TGF-β蛋白强阳性表达,E-cadherin蛋白弱阳性表达;顺铂组SIX1和E-cadherin蛋白阳性表达,TGF-β蛋白强阳性表达;Rg3组SIX1蛋白弱阳性表达,E-cadherin和TGF-β蛋白强阳性表达.顺铂组及Rg3组SIX1蛋白及mRNA表达水平均明显低于对照组(P均<0.05),且Rg3组均明显低于顺铂组(P均<0.05);顺铂组及Rg3组E-cadherin蛋白及mRNA表达水平均明显高于对照组(P均<0.05),且Rg3组明显高于顺铂组(P均<0.05);3组间TGF-β蛋白及mRNA表达水平比较差异均无统计学意义(P均>0.05).结论 Rg3能够通过下调SIX1表达起到抑制人喉鳞癌细胞上皮-间质转化的作用,且其作用强于顺铂.

Objective: Limited information is available on the use of dupilumab for the treatment of atopic dermatitis (AD) in the Chinese population. Methods: We analyzed laboratory data from a previously published randomized, double-blind phase III trial (NCT03912259) to provide further insight into the safety of dupilumab in Chinese adults with moderate to severe AD. The trial participants received either 300 mg of dupilumab or placebo every 2 weeks for 16 weeks. Hematology, blood chemistry, serum thymus and activation-regulated chemokine (TARC), and total immunoglobulin E (IgE) were evaluated. Results: In total, 82 participants received dupilumab and 83 received placebo. With the exception of eosinophil counts of >0.8 × 10 9 /L, which were found less frequently with dupilumab (9.8%) than with placebo (18.7%), the hematology and blood chemistry values were generally stable in both treatment groups. There were no clinically significant differences between the dupilumab and placebo groups, and no participants developed treatment-emergent abnormalities of potential clinical significance. However, compared with placebo, greater decreases in serum lactate dehydrogenase (mean change, −97.4 vs. −33.5 IU/L), TARC (median percent change, −78.6% vs. −30.8%), and total IgE (median percent change, −53.4% vs. −0.2%) were observed with dupilumab than placebo at week 16. Conclusion: Dupilumab demonstrated a favorable laboratory safety profile in Chinese adults with moderate to severe AD.

Animal studies have suggested that transient receptor potential ion channels and G-protein coupled receptors play important roles in itch transmission. TRPV3 gain-of-function mutations have been identified in patients with Olmsted syndrome, which is associated with severe pruritus. However, the mechanisms causing itch remain poorly understood. Here, we show that keratinocytes lacking TRPV3 impair the function of protease-activated receptor 2 (PAR2), resulting in reduced neuronal activation and scratching behavior in response to PAR2 agonists. Moreover, we show that TRPV3 and PAR2 were upregulated in skin biopsies from patients and mice with atopic dermatitis, whereas their inhibition attenuated scratching and inflammatory responses in mouse atopic dermatitis models. These results reveal a previously unrecognized link between TRPV3 and PAR2 in keratinocytes to convey itch information and suggest that a blockade of PAR2 or TRPV3 individually or both may serve as a potential approach for antipruritic therapy in atopic dermatitis.

目的 探讨维持性腹膜透析(peritoneal dialysis,PD)患者低三碘甲状腺原氨酸(triiodothyronine,T3)综合征与残余肾功能及患者存活之间的关系. 方法 收集所有于2009年4月在北京大学第三医院接受维持性PD治疗患者的人口学、甲状腺功能及临床生化学等资料,随访7年.根据残余肾功能水平均分为3组,比较临床特点.采用多元线性回归探讨影响血清游离T3 (free T3,FT3)的因素和COX比例风险模型分析血清FT3对患者生存的影响. 结果 本研究共纳入125例研究对象,其中表现为低T3综合征34例(27.2％).残余肾功能最高组的血清FT3高于其他2组(F=-12.779,P＜0.001),低T3综合征发生率最低(x2=10.175,P=0.038),为14.3％.单因素分析显示血清FT3与残余肾每周尿素清除率(renal Kt/g rKt/V) (r=0.270,P=0.002)、蛋白氮呈现率(protein equivalent of nitrogen appearance,PNA) (r=0.217,P=0.016)、血红蛋白(hemoglobin,HGB) (r=0.183,p=0.044)及血清白蛋白(albumin,ALB) (r=0.424,P＜0.001)呈正相关,而与年龄(r=-0.346,P＜0.001)、血清C反应蛋白(C-reactive protein,CRP)(r=-0.311,P＜0.001)呈负相关.多元线性回归分析显示在校正性别、年龄、ALB、血清CRP、HGB及PNA后,rK t/V仍是影响血清FT3的独立因素(β=0.284,P=0.004),而COX回归分析显示在校正性别、年龄、rKt/V、PNA、HGB、以及血清CRP和ALB等因素后,血清FT3仍能独立地预测患者的生存(HR:0.303,95％ CI:0.103～0.889,P=0.030). 结论 笔者研究表明在维持性PD人群中,低T3综合征的发生与残余肾功能密切相关,血清FT3水平能独立预测患者的死亡风险.

目的探讨维持性血液透析（maintenance hemodialysis,MHD）患者甲状腺激素异常的临床特点及其对生存的影响。方法收集2011年11月～2016年11月在北京大学第三医院进行MHD患者的人口学、甲状腺功能及临床生化等资料,并随访5年。将患者分为正常甲状腺功能、低三碘甲状腺原氨酸（triiodothyronine,T3）综合征、甲状腺机能减退症（以下简称甲减症）等3组,通过单因素方差分析比较其特点,采用多元线性回归来探讨影响血清游离T3（free triiodothyronine,FT3）的因素,基于COX比例风险模型分析血清甲状腺激素对患者生存的影响。结果本研究共纳入研究对象121例,其中表现为低T3综合征者78例（64.50%）,甲减症者15例（12.40%）。与正常组相比,低T3综合征及甲减症组女性比例更高（χ~2=10.082,P=0.006）、年龄更大（F=4.899,P=0.009）,而体质量、血清前白蛋白（prealbumin,PAB）水平更低（F值分别为4.129,6.233;P值分别为0.019,0.003）。多元线性回归分析提示血清CRP和PAB是影响血清FT3水平的独立因素（β值分别为-0.266,0.250;P值分别为0.004,0.022）。COX比例风险模型显示在校正性别、年龄、糖尿病、透析龄以及血红蛋白等因素后,血清FT3仍能独立地影响患者生存（HR 0.343,95%CI 0.130～0.906,P=0.031）,而TSH却不能（HR 0.997,95%CI 0.969～1.026,P=0.831）。结论 MHD患者的甲状腺功能紊乱主要表现为低T3综合征,血清FT3而非TSH能独立地预测患者的全因死亡。

Objective To compare the efficacy and safety of the long-term intermittent maintenance treatment with tacrolimus 0.03％ ointment versus traditional treatment in reducing relapses and prolonging the recurrence interval in children with moderate to severe atopic dermatitis (AD).Methods A two-phase randomized,open-labelled,controlled clinical trial was conducted from September 2012 to November 2013.In the first phase,a total of 171 children aged 2-15 years with moderate to severe AD were enrolled from 7 hospitals in China,and received conventional treatment with tacrolimus 0.03％ ointment twice a day for 2-6 weeks.At the end of the treatment,the patients who achieved an investigator's global assessment (IGA) score ≤ 2 (n =125) were randomly classified into 2 groups to receive the second-phase treatment:test group (n =62) receiving intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week (Monday and Thursday),and control group (n =63) receiving no treatment.If the patients in the 2 groups experienced relapse,they received conventional treatment with tacrolimus 0.03％ ointment twice a day.The overall observation period was 6 months.The primary endpoint was the time to the first relapse,which was defined as the number of days from the end of the first-phase treatment to the first relapse.The secondary endpoints included the number of relapses at the second-phase trial,the disease severity at the time of relapse,the duration of relapse,the pruritus score at the time of relapse,the total amount of tacrolimus ointment used,the total response rate at the second-phase trial,and the incidence of adverse events.Results A total of 125 children with AD were enrolled into the second-phase trial,and 121 of them completed the follow-up.Among the 121 patients,the recurrence rate was significantly lower in the test group (25/60,41.7％) than in the control group (46/61,75.4％;x2 =14.20,P ＜ 0.001).The time to the first relapse was significantly longer in the test group (46.9 ± 37.7 d) than in the control group (28.8 ± 32.3 d;Z =1 093.50,P =0.020).The total number of recurrence was 31 and 86 in the test group and control group respectively,and the mean number of recurrence in each patient was significantly lower in the test group (0.52 ± 0.68) than in the control group (1.41 ± 1.23,t =4.96,P ＜ 0.001).There were no significant differences between the two groups regarding disease severity during relapse (eczema area and severity index:Z =971.50,P =0.39),duration of relapse (Z =747.00,P =0.07),and pruritus score during relapse (Z =894.00,P =0.95).The therapeutic drug was tolerated well in all the children,and no tacrolimus-related serious adverse events occurred.Conclusion The intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week for 6 months can effectively and safely prevent and reduce relapses,and prolong the recurrence interval in children with moderate to severe AD.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity reaction characterized by maculopapular rash, exfoliative dermatitis, lymphadenopathy, fever, eosinophilia, and involvement of internal organs. Evidence for reactivation of herpes family viruses has been observed in some DRESS patients, and activated CD8+ T lymphocytes are largely directed against Epstein-Barr virus. Here, we report two cases complicated with this infection. Both patients received antibiotics and non-steroidal anti-inflammatory drugs. These patients manifested clinically with high fever, facial edema, diffuse pruritic erythroderma and maculopapules over the entire body, purpuric rashes in both lower limbs and lymphadenopathy of cervical and inguinal nodes. Laboratory tests revealed abnormal liver function, blood eosinophils, and ferritin levels. The patients recovered completely; however, the female patient developed hemophagocytic syndrome on the 15th day of illness. She developed new itchy rash, and laboratory tests rapidly worsened with fibrinogen levels dramatically reduced to 0.61 g/L. Bone marrow aspiration revealed an increased number of macrophages with hemophagocytosis and a reversed CD4/CD8 ratio of 0.45. These cases suggest that human herpes virus and coagulation function evaluations are necessary in DRESS patients.

目的 观察氟比洛芬酯联合七叶皂苷钠对阻塞性睡眠呼吸暂停低通气综合征多平面术后镇痛效果.方法 选取我院收治的行多平面手术的重度OSAHS 90例,按照随机数字表法分为对照组、氟比洛芬酯组与氟比洛芬酯联合七叶皂苷钠组(联合用药组),每组各30例.对照组术后12 h口服氨酚羟考酮5 mg、3/d,连用3 d;氟比洛芬酯组与联合用药组均于术前30 min、术后12、24、36、48、60、72 h静脉注射氟比洛芬酯50 mg,在此基础上,联合用药组术后3 d静脉滴注七叶皂苷钠10 mg/d,治疗3 d.记录术后24、36、48、72、96 h视觉模拟评分(visual analog scale,VAS),检测术前0.5 h、术后24 h白细胞介素(Interleukin,IL)-2、IL-6水平变化,观察呼吸暂停低通气指数(apnea-hypopnea index,AHI)、术中出血量、手术时间及不良反应发生情况.结果 与对照组比较,氟比洛芬酯组、联合用药组术后24、36、48、72、96 h VAS评分均明显降低,差异有统计学意义(P<0.05);与氟比洛芬酯组比较,联合用药组术后24、36、48、72、96 h VAS评分下降,差异有统计学意义(P<0.05).与对照组比较,氟比洛芬酯组、联合用药组术后24 h IL-2水平升高,IL-6水平降低,差异有统计学意义(P<0.05);与氟比洛芬酯组比较,联合用药组术后24 h IL-2水平升高,IL-6水平下降,差异有统计学意义(P<0.05).三组AHI、术中出血量、手术时间、不良反应发生率比较差异无统计学意义(P>0.05).结论 氟比洛芬酯联合七叶皂苷钠对重度OSAHS多平面术后镇痛效果肯定,临床可推广应用.