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Summary: Background: Dupilumab is an antibody against interleukin‐4 receptor α, used in the treatment of atopic dermatitis (AD). Objectives: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate‐to‐severe AD. Methods: In this randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0–1 and a reduction from baseline of ≥ 2 points at week 16. Results: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37–32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75–55·97; P < 0·001) and had ≥ 3‐point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26–55·34; P < 0·001) and ≥ 4‐point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69–45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment‐emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group. Conclusions: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile. What is already known about this topic?Two randomized, placebo‐controlled phase III trials (SOLO 1 and SOLO 2) have demonstrated that dupilumab is effective and safe when used in the treatment of atopic dermatitis in adults.However, very few Chinese participants were included and, therefore, the efficacy and safety of dupilumab in this population is unclear. What does this study add?The findings of this randomized, placebo‐controlled phase III trial show that dupilumab is effective in improving the signs and symptoms of atopic dermatitis in adult Chinese patients and has a favourable safety profile in this population. Plain language summary available online [ABSTRACT FROM AUTHOR]

Objective: To estimate the incidence of urinary incontinence (UI), including its subtypes stress UI (SUI), urgency UI (UUI) and mixed UI (MUI), and to examine risk factors for de novo SUI and UUI in Chinese women. Design: Nationwide longitudinal study. Setting: Six geographic regions of China. Participants: Women aged ≥20 years old were included using a multistage, stratified, cluster sampling method. Methods: This study was conducted between May 2014 and March 2016, with follow up in 2018. Data on demographics, medical history, lifestyle and physiological and anthropometric information were collected. Main outcome measurements: Incidence, rate ratio (RR). Results: Analyses included 24 985 women (mean age 41.9 years).The follow‐up response rate was 55.5%, median follow‐up time was 3.7 years. The standardised incidences of UI, SUI, UUI and MUI were 21.2, 13.1, 3.0 and 5.1 per 1000 person‐years, respectively. Risk factors for de novo SUI included delivery pattern (vaginal spontaneous delivery RR 2.12, 95% CI 1.62–2.78 and instrumental delivery RR 3.30, 95% CI 1.99–5.45), high body mass index (BMI) (overweight RR 1.52, 95% CI 1.33–1.74 and obesity RR 1.67, 95% CI 1.32–2.11), cigarette smoking (RR 1.54, 95% CI 1.12–2.12), chronic cough (RR 1.44, 95% CI 1.17–1.76), diabetes (RR 1.33, 95% CI 1.10–1.60) and older age (50–59 years RR 1.49, 95% CI 1.16–1.90 and 60–69 years RR 1.61, 95% CI 1.22–2.13).The risk factors significantly associated with de novo UUI were age (RR increased from 1.21, 95% CI 0.74–1.99, at 30–39 years to 6.3, 95% CI 3.85–10.30, at >70 years) and diabetes (RR 1.48, 95% CI 1.05–2.09). Conclusions: The incidence of female UI is 21.2 per 1000 person‐years in China. Delivery (vaginal spontaneous delivery, instrumental delivery), high BMI, cigarette smoking, chronic cough, diabetes and older age were risk factors. The incidence of female urinary incontinence was 21.2 per 1000 person‐years in China. Delivery, BMI, diabetes and old age are risk factors. The incidence of female urinary incontinence was 21.2 per 1000 person‐years in China. Delivery, BMI, diabetes and old age are risk factors. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence, risk factors and burden of symptomatic pelvic organ prolapse (POP) in adult Chinese women.Design: A nationwide cross-sectional study.Setting: Six geographic regions of mainland China.Participants: Women aged ≥20 years old were included using a multistage, stratified, cluster sampling method from February 2014 through March 2016.Methods: We conducted a nationwide epidemiological survey. 'Symptomatic POP' was determined by a screening questionnaire and physical examination.Main Outcome Measurements: Prevalence, odds ratio (OR).Results: A total of 55 477 women (response rate, 92.5%; mean age, 45.1 years old) were included. The prevalence of symptomatic POP was 9.6% (95% CI 9.3-9.8%) and it increased with age in each stage (P < 0.05). Symptomatic POP-Q stage II, which mainly involved anterior compartment prolapse, was the most common (7.52%). Minor/moderate burden of symptomatic POP was the most common, with a prevalence of 9.7% (95% CI 9.5-10.0%). The odds for each type of symptomatic POP increased with age (>50 vs 20-29 years old in symptomatic POP-Q stage II or higher, OR increased from 1.34 [95% CI 1.32-1.45] to 7.34 [95% CI 4.34-12.41]) and multiple vaginal deliveries (multiparous [≥3] vs nulliparous in symptomatic POP-Q stage II or higher, OR increased from 1.91 [1.71-2.13] to 2.78 [2.13-3.64]).Conclusions: We found a lower prevalence of symptomatic POP than that found in other surveys. The main type of symptomatic POP was anterior compartment prolapse, indicating that it should be considered first. Older age and multiple vaginal deliveries increased the odds of each type of symptomatic POP.Tweetable Abstract: The prevalence of female symptomatic pelvic organ prolapse (POP) was 9.6% in China. It is related to old age and multiple vaginal deliveries. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to test whether orosomucoid like 3 ( ORMDL3) and 17q21 variants are associated with susceptibility to ankylosing spondylitis (AS) in a Chinese population. Method: A total of 753 unrelated AS patients and 1120 ethnically matched healthy controls were recruited. Seven single nucleotide polymorphisms (SNPs: rs7216389, rs12603332, rs12936231, rs9303277, rs11557467, rs1007654, and rs17608925), which were selected from chromosome 17q21 containing the genes ORMDL3, GSDMB, ZPBP2, and IKZF3, were genotyped by the Taqman SNP genotyping assay. Results: Five of the SNPs (rs7216389, rs12603332, rs12936231, rs9303277, and rs11557467) were associated with AS (all p ≤ 0.01), especially in males (all p < 0.001). Of these, rs7216389, rs12603332, rs12936231, and rs11557467 were strongly associated with severity of the disease based on radiographic findings (p < 0.05). Conclusions: Our study confirmed that variants in chromosome 17q21 are significantly associated with AS in a Chinese Han population. [ABSTRACT FROM AUTHOR]

Background:ABO blood group is associated with aetiology of nasopharyngeal carcinoma (NPC); however, the effect of it on survival of patients diagnosed with NPC has not been explored.Methods:We retrospectively analysed two cohorts of southern Chinese patients with WHO histological type III: intensity-modulated radiotherapy (IMRT) cohort, 924 patients; and conventional radiotherapy (CRT) cohort, 1193 patients. Associations of ABO blood group with survival were estimated using Cox regression.Results:In IMRT cohort, we observed significant associations of blood type A with overall survival (OS) and distant metastasis-free survival (DMFS), compared with type O, after adjusting for prognostic factors. Compared with non-A blood types (B, AB, and O), type A patients had significantly lower OS and DMFS (adjusted hazard ratio (HR)=1.49, 95% CI 1.03-2.17, P=0.036; HR=1.68, 95% CI 1.13-2.51, P=0.011, respectively); similar results were obtained in CRT cohort. Subgroup analyses of the entire population showed that lower OS conferred by blood type A was not significantly modified by age, smoking status, drinking status, immunoglobulin A against Epstein-Barr virus viral capsid antigen (VCA-IgA) titre, or chemotherapy; however, lower OS was not observed in female patients or patients with early clinical stage disease.Conclusion:ABO blood group is associated with survival in NPC; patients with blood type A had significantly lower OS and DMFS than patients with non-A blood types. [ABSTRACT FROM AUTHOR]

Background:Family history of cancer is associated with developing nasopharyngeal carcinoma (NPC); however, the impact of it on survival among established NPC patients remains unknown.Methods:We retrospectively analysed 1773 southern Chinese patients. Associations between a first-degree family history of NPC and overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated by Cox regression.Results:Among 1773 patients, 207 (11.7%) reported a first-degree family history of NPC. Compared with patients without a family history, the adjusted hazard ratios among those with it were 0.60 (95% confidence interval (CI), 0.37-0.98; P=0.040) for OS, 0.52 (95% CI, 0.24-1.12; P=0.096) for LRFS and 0.51 (95% CI, 0.27-0.97; P=0.040) for DMFS. There were trends for improving OS, LRFS and DMFS with increasing number of affected relatives (Ptrend: 0.050, 0.114 and 0.044, respectively). But no significant benefits of family history in second- or third-degree relatives were observed. In subgroup analysis, we observed the effects of family history with restriction to male patients and those of advanced stage and treated with conventional radiotherapy and addition of chemotherapy.Conclusion:A first-degree family history of NPC is associated with improved survival of patients. [ABSTRACT FROM AUTHOR]

Background Recently, we have reported filaggrin mutations ( FLG) of atopic dermatitis in southern China. However, there have been few detailed reports of FLG mutations of patients with AD in northern China by now. Objectives The present aim was to establish the mutation spectrum of FLG gene in AD patients in northern China. Methods A total of 339 cases met Hanifin and Rajka diagnostic criteria of AD were recruited. A comprehensive sequencing of the entire FLG coding region in these patients was conducted. All detected FLG null mutations were screened in a cohort of 301 normal controls. Results Seven novel mutations (478insA, Q1070X, 4026delT, Q1712X, Q2397X, 7145del4 and 8001del4) and eleven reported mutations (3222del4, 3321delA, 4271delAA, S1515X, Q1790X, 5757del4, 6834del5, Q2417X, E2422X, 7945delA and K4671X) in AD were identified. Mutations 3321delA and K4671X were two of the most common mutations in AD. FLG null mutations were present in 26.0% of AD patients. FLG null alleles (compound genotypes) were significantly higher in AD ( P < 0.001) than in the controls. The compound genotypes for all FLG variants were significantly associated with IV ( P < 0.001) and palmar hyperlinearity ( P < 0.001). The common mutation, K4671X, was significantly associated with AD-coexistent allergic rhinitis ( P = 0.005). Conclusions Our study increases the total number of FLG mutations. We clearly demonstrated that FLG loss-of-function mutations were significantly associated with AD in northern China. The FLG null mutations in the Chinese population differed not only from that in the European population but also from that in sub-populations of Asians outside of the Chinese mainland. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-13 plays an important role in the pathogenesis of asthma. A polymorphic variant of human IL-13 R130Q, results in substitution of an arginine with a glutamine was shown to be associated with asthma in Chinese Han nationality. We examined the functional consequences of this variant in vitro to investigate whether this variant enhanced functional activity compared with wild type IL-13. The wild-type and mutant IL-13 genes were amplified from the plasmid of pET22b-hIL-13 by PCR and site-directed mutagenesis PCR. Both the PCR product and the vector pET28a(+) were digested by the NdeI and BamHI. Then the PCR product was cloned in the prokaryotic expression vector of pET28a(+). The plasmids were constructed and transformed into E. coli BL21(DE3).The positive clones were selected, and tested by sequencing. Peripheral blood mononuclear cells (PBMCs) from healthy participants were isolated and cultured with increasing concentrations of recombinant WT IL-13 and IL-13 R130Q. IgE was detected with ELISA kit in the supernatants. Recombinant WT IL-13 and IL-13 R130Q were successfully expressed into the prokaryotic expression system and their biological activity was consistent with standard protein. Our results show that IL-13 R130Q is more active than WT IL-13 in inducing hydrocortisone-dependent IgE synthesis. There were statistical significances between them. IgE induction by physiologic concentrations was obviously increased. IL-13 R130Q has increased activity compared with wild type IL-13 in vitro. And IL-13 R130Q may be used for new target of asthma for diagnosis and therapy in the future. [ABSTRACT FROM AUTHOR]

The effect of race on Crohn's disease (CD) remains uncertain. This study compared the characteristics of American white patients and Chinese patients with CD. A retrospective chart review was conducted for patients who required management of colorectal CD between 1985 and 2004 at either Cleveland Clinic Florida (CCF) or at the 301 Hospital in China. Data included a family history of CD, smoking history, location of the CD and histopathology. The mean age of onset in the 153 patients was 29.8 ± 16.4 years for American white patients and 32.4 ± 15.3 years for Chinese patients (not significant). Sixty per cent of American white patients were women vs 37% of Chinese patients ( P = 0.003). Twelve per cent of American white patients vs 1% of Chinese patients had a family history of CD ( P = 0.016). American white patients had significantly higher rates of arthritis (32% vs 4%), abscess (19% vs 0%), rectal and perineal fistula (52% vs 0%), and disease involving the colon and rectum when compared with Chinese patients (all P < 0.05). American white patients had more colorectal sites involved and higher rates of extraintestinal diseases (40% vs 20%) than Chinese patients (all P < 0.05). Chinese patients had higher rates of ileocaecal disease (82% vs 52%) and deep ulcers (66% vs 24%) in the colorectum (all P < 0.001). There were no statistical differences in the incidence of smoking, perforation, intra-abdominal fistula, stenosis, bowel obstruction, toxic megacolon or granuloma formation. This study found that colorectal CD had a more severe clinical presentation and pathological involvement in American white patients than in Chinese patients. [ABSTRACT FROM AUTHOR]

The PTGDR gene has been suggested to be an asthma susceptibility gene in previous genome-wide linkage studies as well as in functional studies in a mouse model of asthma. Recently, promoter polymorphisms of the PTGDR gene have been reported to be associated with asthma in American and European populations. In order to determine the association of PTGDR promoter polymorphisms and asthma susceptibility in a Chinese Han population, three promoter single nucleotide polymorphisms (SNP) –549T/C, –441C/T, and –197T/C were genotyped in 336 patients with asthma and 264 healthy controls. Asthma was diagnosed according to the American Thoracic Society (ATS) criteria. SNPs –549T/C and –441C/T were genotyped by Tetra-primer Amplification Refractory Mutation System PCR method and –197T/C by polymerase chain reaction-restriction fragment length polymorphism method. Unlike the results observed in American and European populations, none of the three SNPs nor any haplotypes in the PTGDR promoter region were found to be associated with asthma susceptibility in this Chinese Han population (all P-value > 0.05). The frequencies for both high-transcriptional-efficiency haplotype (CCC) and low-transcriptional-efficiency haplotype (TCT) were lower than 1% in patients and controls, significantly different from those observed in American and European populations. These results suggest that the three PTGDR gene promoter polymorphisms studied are not important risk factors for asthma susceptibility in the Chinese Han population. [ABSTRACT FROM AUTHOR]

Asthma is a complex polygenic disease with gene–environment interactions being important. It has been previously suggested that ADAM33, which is a member of a gene family that encodes membrane-anchored proteins with a disintegrin and a metalloprotease domain, is primarily expressed in lung fibroblasts and bronchial smooth muscle cells and has been associated with airway remodelling and bronchial hyperresponsiveness. A significant association has previously been demonstrated between single nucleotide polymorphisms (SNPs) and haplotypes of the ADAM33 and asthma in ethnically diverse populations. To assess whether SNPs or haplotypes of ADAM33 are related to asthma in a Chinese Han population, we genotyped three SNPs of ADAM33 (7575G/A in intron 6, 11188A/T in intron 19, and 12433T/C in exon 20) in a case-control study involving 296 patients with asthma and 270 healthy controls. No significant association was detected between these three SNPs and asthma susceptibility in the Chinese population. [ABSTRACT FROM AUTHOR]