Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

BACKGROUND: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. OBJECTIVE: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. METHODS: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. RESULTS: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. CONCLUSIONS: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

Prevalence and associated factors of sexually transmitted infections among methamphetamine users in Eastern China: a cross-sectional study.

BACKGROUND: The reported incidence of sexually transmitted infections (STIs) in China has been increasing over the last decades, especially among drug users, which has become one of the main burdens of public health in China. This study was conducted to estimate the prevalence and associated factors of STIs among non-injecting methamphetamine (MA) users in Eastern China. METHODS: A cross-sectional survey was conducted among 632 MA users in Eastern China in 2017. Demographic characteristics, sexual behaviors, behaviors of MA use and sexual health knowledge were collected through questionnaire. First pass urine specimens were collected and detected for deoxyribonucleic acid (DNA) of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) with Nucleic Acid Amplification Technology (NAAT), while blood specimens were collected and detected for antibodies of Human immunodeficiency virus (HIV), Herpes simplex virus type-2 (HSV-2), and syphilis with enzyme-linked immune sorbent assay (ELISA). RESULTS: Among the 632 MA users, 464 (73.42%) were males, 60.92% were < 35 years of age, 546 (86.39%) were Shandong residents. 317 (50.16%, 95% CI 46.26-54.06%) participants were tested positive for at least one kind of STIs, including 242 (38.29%, 95% CI 34.50-42.08%) for HSV-2, 107 (16.93%, 95% CI 14.01-19.85%) for active syphilis, 46 (7.28%, 95% CI 5.25-9.31%) for treated syphilis, 40 (6.33%, 95% CI 4.43-8.23%) for CT, 6 (0.95%, 95% CI 0.19-1.71%) for HIV, and 3 (0.47%, 95% CI 0.06-1.00%) for NG infection. 99 (15.66%, 95% CI 12.83-18.49%) participants were co-infected with two kinds of STIs, including 91 (14.40%, 95% CI 11.66-17.14%) participants were co-infected with HSV-2 and syphilis. 14 (2.22%, 95% CI 1.07-3.37%) participants were co-infected with three kinds of STIs, and 4 HIV positive participants were co-infected with both syphilis and HSV-2. In the multiple logistic regression analysis, the results showed that females (adjusted OR [AOR] = 7.30, 95% CI 4.34-12.30) and individuals ≥ 35 years of age (AOR = 2.97, 95% CI 2.04-4.32) were more likely to test positive for STIs among MA users, whereas participants who acquired sexual health knowledge primarily from the Internet (AOR = 0.57, 95% CI 0.40-0.82) and those whose regular partners did not use drugs (AOR = 0.59, 95% CI 0.37-0.94) were less likely. CONCLUSIONS: This study found that the prevalence of HSV-2 and syphilis are alarming high among non-injecting MA users in Shandong Province in Eastern China. The prevention and control intervention of STIs among MA users in Shandong were needed, especially on females and MA users ≥ 35 years of age.

A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis.

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.

Consensus on Pre-examination and Triage in Clinic of Dermatology During Outbreak of COVID-19 From Chinese Experts.

The 2019 novel coronavirus infection has brought a great challenge in prevention and control of the national epidemic of coronavirus disease 2019 (COVID-19) in China. During the fight against the epidemic of COVID-19, properly carrying out pre-examination and triage for patients with skin lesions and fever has been a practical problem encountered in hospitals for skin diseases as well as clinics of dermatology in general hospitals. Considering that certain skin diseases may have symptom of fever, and some of the carriers of 2019 novel coronavirus and patients with COVID-19 at their early stage may do not present any symptoms of COVID-19, to properly deal with the visitors to clinics of dermatology, the Chinese Society of Dermatology organized experts to formulate the principles and procedures for pre-examination and triage of visitors to clinics of dermatology during the epidemic of COVID-19.

[Observation on therapeutic effect of filiform fire needle assisted 308 nm excimer laser on vitiligo of different parts].

OBJECTIVE: To compared the therapeutic effect between filiform fire needle assisted 308 nm excimer laser and simple 308 nm excimer laser on vitiligo of different parts. METHODS: Target lesions of 134 patients were divided into an observation group and a control group according to the principle of self-controlled, 201 pieces in each one. In the observation group, filiform fire needle was performed at target lesions. Then target lesions both of the two groups were irradiated with 308 nm excimer laser at the same time. Once every 2 weeks, totally 10 treatments were required. The effective rate and effective rate, color recovery rate and responding time of different parts in the two groups were evaluated 2 weeks after treatment. RESULTS: The effective rate in the observation group was 82.59% (166/201), which was higher than 68.16% (137/201) in the control group (P<0.01). The effective rate of face-neck, trunk, limbs and hand-foot were 90.32%, 81.63%, 81.48% and 58.62% respectively in the observation group, which were higher than 82.80%, 69.39%, 51.85% and 31.03% in the control group (P<0.01, P<0.05). The color recovery rate of different parts in the observation group was higher than the control group, and the effect was faster in the observation group (P<0.01, P<0.05). CONCLUSION: Filiform fire needle as an adjunctive therapy, combined with 308 nm excimer laser are more effective than simple 308 nm excimer laser for vitiligo of different parts. Combination therapy has a shorter responding time, the face-neck has the best effect and hand-foot has poor effect.

Efficacy and safety of Run Zao Zhi Yang capsule on chronic eczema: a multiple-center, randomized, double-blind, placebo-controlled clinical study.

Background: Run Zao Zhi Yang capsule (RZZYC) has been widely applied for eczema treatment as a traditional Chinese medicine, while its efficacy has not been scientifically investigated. Objective: We conducted this multiple-centers, randomized, double-blind, placebo-controlled study to investigate the effectiveness and safety of RZZYC on the treatment of patients with mild to moderate chronic eczema. Methods: 240 patients were randomly assigned into the experimental group and the placebo group. The primary efficacy indicator was the Eczama Area and Severity Index (EASI) score at week 4. The patient with an EASI score that decreases more than 95% from baseline (EASI 95) was judged as cured. The cured patients were followed up for another 8 weeks. The differences on EASI, Visual Analogue Score (VAS), and Dermatology Life Quality Index (DLQI) score were compared. Results: The proportions of EASI 95 and EASI 60 in the experimental group were significantly higher than those of the control group at week4 (p = .002 and p < .001, respectively), the VAS score decreased more significantly in the experimental group at week 4. After 8 weeks follow-up, no difference on recurrence rate and adverse event rate between the two groups was observed. Conclusion: RZZYC provides a good effect on the treatment of mild-to-moderate chronic eczema with a low recurrence and tolerable adverse events, and is a potential treatment that may be implemented in clinical practice.

Silencing NLRC5 inhibits extracellular matrix expression in keloid fibroblasts via inhibition of transforming growth factor-ß1/Smad signaling pathway.

Dermal fibrosis is characterized by collagen accumulation and hyperproliferation of fibroblasts. NLRC5, as the largest member of nucleotide-binding domain and leucine-rich repeat (NLRs) family, has recently been implicated in the development of hepatic fibrosis. However, the role of NLRC5 in dermal fibrosis remains unknown. Therefore, herein, we investigated the effects of NLRC5 on keloid fibroblasts (KFs) and transforming growth factor-ß1 (TGF-ß1)-induced collagen expression and explored the underlying mechanism. We observed that NLRC5 mRNA and protein levels were highly expressed in KFs, silencing NLRC5 greatly suppressed TGF-ß1-induced KFs proliferation. Silencing NLRC5 also obviously inhibited the expression of type I collagen, CTGF and α-smooth muscle actin (α-SMA) in human KFs induced by TGF-ß1, as well as the expression of TGF-ß receptor I and II. Furthermore, silencing NLRC5 suppressed the expression of TGF-ß1-induced Smad2 and Smad3 phosphorylation in human KFs. Taken together, our study suggest that silencing NLRC5 reduced ECM expression in KFs through inhibiting the TGF-ß1/Smad signaling pathway. Therefore, NLRC5 may represent a promising target for treatment of the keloid disease.

Glycyrrhizin combined with acitretin improve clinical symptom of psoriasis via reducing Th17 cell differentiation and related serum cytokine concentrations.

OBJECTIVE: To evaluate the effect of compound glycyrrhizin in combination with acitretin on Th17 cell and related cytokines expressions in patients with psoriasis. METHODS: A total of 100 patients with psoriasis were enrolled in our study and randomized into an acitretin (Aci) group (n = 50) and a compound glycyrrhizin/acitretin combined treatment (Aci + Glyc) group (n = 50). Both groups were medicated with 3 × 10 mg acitretin per day for 8 weeks but the (Aci + Glyc) group received additionally 3 × 75 mg compound glycyrrhizin every day. A total of 50 healthy individuals were selected as the control group. The peripheral blood Th17 cell percentage as well as the IL-6, IL-17, IL-22 and TGF-ß serum concentrations in addition to PASI scores were determined before and after medications. RESULTS: The Th17 cell percentages and the serum concentrations of IL-6, IL-17, IL-22 and TGF-ß in the Aci and Aci + Glyc groups were significantly higher than those in the control group before treatments (P < 0.05) and were significantly declined after the treatments (P < 0.05), but to a higher extend in the Aci + Glyc group (P < 0.05). The clinical treatment effective rates in the Aci group and the Aci + Glyc group were 76.0% and 90.0% (P < 0.05) compared to invalid events after treatments. CONCLUSIONS: Compound glycyrrhizin in combination with acitretin can improve the clinical efficacy significantly when compared with of the solely acitretin medication for psoriasis treatments via down regulating Th17 cell differentiation.

Identification of new susceptibility loci for IgA nephropathy in Han Chinese.

IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.

Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population.

To identify susceptibility loci for vitiligo, we extended our previous vitiligo genome-wide association study with a two-staged replication study that included 6,857 cases and 12,025 controls from the Chinese Han population. We identified three susceptibility loci, 12q13.2 (rs10876864, P(combined)=8.07 × 10(-12), odds ratio (OR)=1.18), 11q23.3 (rs638893, P(combined)=2.47 × 10(-9), OR=1.22), and 10q22.1 (rs1417210, P(combined)=1.83 × 10(-8), OR=0.88), and confirmed three previously reported loci for vitiligo, 3q28 (rs9851967, P(combined)=8.57 × 10(-8), OR=0.88), 10p15.1 (rs3134883, P(combined)=1.01 × 10(-5), OR=1.11), and 22q12.3 (rs2051582, P(combined)=2.12 × 10(-5), OR=1.14), in the Chinese Han population. The most significant single-nucleotide polymorphism in the 12q13.2 locus is located immediately upstream of the promoter region of PMEL, which encodes a major melanocyte antigen and has expression loss in the vitiligo lesional skin. In addition, both 12q13.2 and 11q23.3 loci identified in this study are also associated with other autoimmune diseases such as type 1 diabetes and systemic lupus erythematosus. These findings provide indirect support that vitiligo pathogenesis involves a complex interplay between immune regulatory factors and melanocyte-specific factors. They also highlight similarities and differences in the genetic basis of vitiligo in Chinese and Caucasian populations.

Infliximab monotherapy for Chinese patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled multicenter trial.

BACKGROUND: Tumor necrosis factor-α is a key mediator in the pathogenesis of psoriasis. Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-α. The purpose of this study was to validate the efficacy and safety of 5 mg/kg infliximab therapy in Chinese patients with moderate to severe plaque psoriasis. METHODS: In this multicenter, double-blind, placebo-controlled trial, 129 patients with moderate-to-severe psoriasis were randomized to the induction therapy (weeks 0, 2 and 6) with infliximab 5 mg/kg (n = 84) or placebo (n = 45), followed with infliximab 5 mg/kg scheduled at week 14 and week 22 in the infliximab group, and infliximab 5 mg/kg scheduled at weeks 10, 12 and 16 in the placebo group. The primary end point was the proportion of patients who achieved at least 75% improvement in Psoriasis Area and Severity Index (PASI 75 response rate) from baseline at week 10. RESULTS: At week 10, 81.0% of patients treated with infliximab (5 mg/kg) achieved a 75% or greater improvement compared with 2.2% of patients treated with placebo (P < 0.001). A significant improvement in PASI, Physician's Global Assessment (PGA) and Dermatology Life Quality Index (DLQI), was seen from week 6 through week 14 in the infliximab group compared with the placebo group. Through week 22, PASI, PGA, DLQI were well maintained. The incidence of adverse events for the infliximab treatment group was slightly higher in comparison to the placebo treatment group during the first 10 weeks without statistical significance. However, there were 3 cases of tuberculosis that developed during the 26 weeks treatment with infliximal. CONCLUSIONS: Infliximab treatment was effective as induction and maintenance treatments for Chinese patients with moderate to severe plaque psoriasis. Most drug-induced adverse events were mild to moderate, and well tolerated. Screening for tuberculosis is essential and prophylactic treatment should be given if necessary.

Association of the HLA-DRB1 locus with syphilis in a Chinese population.

BACKGROUND: Syphilis is a sexually transmitted infection (STI) caused by the Treponema pallidum subspecies pallidum spirochete bacterium. The association of human leukocyte antigen (HLA) with syphilis has been reported in several populations, but not in the Chinese population. Furthermore, serology methods have mostly been used in previous studies investigating the association between STIs and HLA alleles. The objective of this study was to analyze the association of the HLA-DRB1 alleles and susceptibility to syphilis in the Chinese population. METHODS: A polymerase chain reaction with sequence-specific primers (PCR-SSP) method was used to genotype HLA-DRB1 alleles in 196 syphilis patients and 500 healthy controls. RESULTS: The HLA-DRB1*14 allele was more prevalent in syphilis patients than in the healthy controls (p=0.013; corrected p<0.05). CONCLUSIONS: The allele HLA-DRB1*14 was found to be associated with susceptibility to syphilis in the Chinese population.

Association analyses identify six new psoriasis susceptibility loci in the Chinese population.

We extended our previous genome-wide association study for psoriasis with a multistage replication study including 8,312 individuals with psoriasis (cases) and 12,919 controls from China as well as 3,293 cases and 4,188 controls from Germany and the United States and 254 nuclear families from the United States. We identified six new susceptibility loci associated with psoriasis in the Chinese study containing the candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A (combined P < 5 × 10⁻8) and replicated one locus, 5q33.1 (TNIP1-ANXA6), previously reported (combined P = 3.8 × 10⁻²¹) in the European studies. Two of these loci showed evidence for association in the German study at ZNF816A and GJB2 with P = 3.6 × 10⁻³ and P = 7.9 × 10⁻³, respectively. ERAP1 and ZNF816A were associated with type 1 (early onset) psoriasis in the Chinese Han population (test for heterogeneity P = 6.5 × 10⁻³ and P = 1.5 × 10⁻³, respectively). Comparisons with the results of previous GWAS of psoriasis highlight the heterogeneity of disease susceptibility between the Chinese and European populations. Our study identifies new genetic susceptibility factors and suggests new biological pathways in psoriasis.

Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.

Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21.

We report the first large genome-wide association study (GWAS) in a Chinese population to identify susceptibility variants for psoriasis using a two-stage case-control design. In the first stage, we carried out a genome-wide association analysis in 1,139 cases and 1,132 controls of Chinese Han ancestry using Illumina Human 610-Quad BeadChips. In the second stage, we took top SNPs forward for replication in two independent samples of 5,182 cases and 6,516 controls of Chinese Han ancestry, and 539 cases and 824 controls of Chinese Uygur ancestry. In addition to the strong replication for two known susceptibility loci MHC (rs1265181, P = 1.93 x 10(-208), OR = 22.62) and IL12B (rs3213094, P(combined) = 2.58 x 10(-26), OR = 0.78), we identified a new susceptibility locus within the LCE gene cluster on 1q21 (rs4085613, P(combined) = 6.69 x 10(-30), OR = 0.76).