Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To determine the expression of adenylate cyclase genes ADCY2/4/5/8 in cutaneous melanoma, to explore their roles and mechanisms of action, and to verify their effect on the proliferation and migration of the melanoma cell line A375.Methods:Data on the mRNA and protein expression of ADCY2/4/5/8, as well as the correlation between gene expression and prognosis, were analyzed through the Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) databases; ADCY2/4/5/8 gene methylation and mutation status were analyzed through the UALCAN, DeMth, and cBioPortal databases; Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on the ADCY2/4/5/8 genes using the DAVID and STRING databases. qPCR was conducted to determine the relative mRNA expression of ADCY2/4/5/8 in the A375 melanoma cells and FF pigmented nevus cells. Cultured A375 cells were divided into experimental groups and control groups to be transfected with ADCY2/4/5/8 overexpression plasmids and empty vectors, respectively. Cell counting kit (CCK8) and Transwell assays were performed to evaluate the effect of ADCY2/4/5/8 overexpression on the proliferation and migration of A375 cells, qPCR was conducted to determine the relative mRNA expression of genes related to the proliferation and migration of A375 cells, and Western blot analysis to determine the expression of cyclic adenosine monophosphate (cAMP) signaling pathway-related proteins in A375 cells after the overexpression of ADCY2/4/5/8. One-way analysis of variance and repeated measures analysis of variance were used for the comparison among multiple groups, and least significant difference- t test was used for multiple comparisons. Results:Bioinformatics analysis based on the GEPIA database showed that the mRNA expression of ADCY2, ADCY4, ADCY5, and ADCY8 was down-regulated in melanoma tissues ( n = 461) compared with normal tissues ( n = 558, P < 0.01) ; stratified analysis showed that the mRNA expression of ADCY2 ( P = 0.015) and ADCY8 ( P = 0.038) was correlated with tumor staging, and the lower the mRNA expression, the later the tumor stage. In the HPA database, the ADCY2/4/5/8 protein expression was reduced in 30 melanoma tissues compared with 30 normal tissues ( P < 0.001). Analysis of the UALCAN and DeMth database data showed elevated methylation levels of ADCY2/4/5/8 in melanoma tissues and metastatic melanoma tissues compared with normal tissues ( P < 0.001). Analysis of the DAVID and STRING database data demonstrated that the ADCY2/4/5/8 gene may inhibit cell proliferation and migration by activating the cAMP signaling pathway. qPCR showed that the relative mRNA expression of ADCY2/4/5/8 was lower in A375 cells than in FF cells. CCK8 assay showed that the survival rates of A375 cells were significantly lower in the ADCY2/4/5/8 overexpression groups than in the corresponding control groups at 48 and 72 hours (all P < 0.05). Transwell assay showed that the number of migratory A375 cells was significantly lower in the ADCY2/4/5/8 overexpression groups than in the corresponding control groups (all P < 0.01). As qPCR revealed, the ADCY2/4/5/8 overexpression groups showed significantly upregulated relative mRNA expression of epithelial cadherin, but significantly downregulated relative mRNA expression of Ki67, vimentin, neural cadherin, and matrix metalloproteinase 2 compared with the corresponding control groups (all P < 0.001). Western blot analysis showed that the protein expression of cAMP and phosphorylated protein kinase A (p-PKA) in A375 cells was significantly higher in the ADCY2/4/5/8 overexpression groups than in the corresponding control groups (all P < 0.001), but there were no significant differences in the PKA protein expression levels between the ADCY2/4/5/8 overexpression groups and the corresponding control groups (all P > 0.05) . Conclusion:The expression of ADCY2/4/5/8 was downregulated in melanoma tissues, and overexpressed ADCY2/4/5/8 could inhibit the proliferation and migration of melanoma cells, suggesting that ADCY2/4/5/8 may serve as potential tumor suppressor genes in the progression of melanoma.

Objective:To investigate the expression, methylation and prognosis of DKK2 in non-small cell lung cancer, and also its effect and correlation with the sensitivity of hypofractionated radiotherapy sensitivity in non-small cell lung cancer.Methods:qPCR, online database and Kaplan-Meier survival curve were used to detect the expression, methylation and prognosis of DKK2 in NSCLC samples. A549 cells was set as the research objects, and cloning formation experiment and Western blot were used to evaluated the effects of DKK2 on hypofractionated radiotherapy in NSCLC.Results:Compared with the normal tissues, the expression of DKK2 mRNA in NSCLC samples was down-regulaged [ (0.00042±0.0001) vs (0.00065±0.0002), P<0.001]. Data taken from an online methylation database showed that compared with normal tissue, DKK2 hypermethylated in NSCLC, and its methylation was significantly negatively correlated with the mRNA expression. Downregulated DKK2 expression was inversely correlated with its methylation status ( P=0.034). The hypofractionated radiotherapy sensitivity of NSCLC patients was 53.3%. Compared with radiosensitivity group, DKK2 mRNA expression was significantly down-regulated in radioresistance group[ (0.00064±0.0002) vs (0.00043±0.0002), P<0.001]. The progression free survival of radiotherapy sensitive group was better than that of radiotherapy resistant group (median PFS: 21.4 months vs 4.6 months). Ectopic expression of DKK2 in A549 lines inhibited colony formation after irradiation with 4 Gy X-ray radiotherapy. Western blot further showed that restoration of DKK2 expression resulted in upregulation of DNA damage markers γ-H2AX[ (1.00±0.24) vs (3.22±0.41), P<0.001], and the difference was statistically significant. Conclusion:DKK2 expression is downregulated in NSCLC due to methylation, which may be acted as an important target to predict the hypofractionated radiotherapy sensitivity of NSCLC.

Objective:To explore the prolonged therapeutic regimen for patients with plaque psoriasis, who showed a positive response to 4-week treatment with tazarotene/betamethasone dipropionate cream, but were not completely cured.Methods:A multicenter, randomized, open-labelled, parallel-controlled clinical study was conducted. A total of 232 patients with plaque psoriasis were collected, who showed a positive response to previous 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured with the psoriasis area and severity index[PASI] improvement rate being 50%-90%. At week 5, they were randomly and equally divided into 2 groups: test group receiving treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream once a day, and control group receiving a sequential regimen of 0.05% tazarotene gel on weekdays once a day followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream on weekends once a day. After 2-and 4-week prolonged treatment, the efficacy and safety of the 2 therapeutic regimens were evaluated and compared. Measurement data were compared between 2 groups by using covariance analysis or t test, and enumeration data were compared by using chi-square test. Results:From the 5th to the 8th week, 200 out of the 232 patients completed the treatment. Data collected from 110 patients in the test group and 112 in the control group were enrolled into the full analysis set, and those from both 113 patients in the test group and control group were enrolled into safety analysis set. After consecutive 6-and 8-week treatment, the decline rates of the PASI score were 73.05% ± 16.69% and 78.46% ± 15.40% respectively in the test group, which were significantly higher than those in the control group (66.73% ± 21.77%, 67.02% ± 34.19%, respectively, both P < 0.05) . After 6-week treatment, the proportion of subjects who achieved PASI90 was significantly higher in the test group (14 cases, 12.7%) than in the control group (5 cases, 4.5%, χ2=4.842, P=0.028) ; After 8-week treatment, the proportions of subjects who achieved PASI75 and PASI90 (61.8%, 23.6%, respectively) were significantly higher in the test group than in the control group (48.2%, 12.5%, respectively, both P < 0.05) . During the consecutive 8-week treatment, there was no significant difference in the incidence rate of adverse reactions between the test group (15.0%) and control group (23.9%, χ2=2.822, P=0.093) . Conclusion:For patients who showed a positive response to 4-week treatment with 0.05%/0.05% tazarotene/betamethasone dipropionate cream, but were not completely cured, the continuous use of 0.05%/0.05% tazarotene/betamethasone dipropionate cream for 4 weeks is a superior therapeutic regimen compared with the sequential regimen of 0.05% tazarotene gel followed by 0.05%/0.05% tazarotene/betamethasone dipropionate cream.

Objective:To evaluate the reporting quality of clinical guidelines on skin diseases published in journals in China.Methods:The CNKI, VIP, Wanfang and SinoMed databases were searched from January 2009 to October 2019 for clinical guidelines on skin diseases published in journals in China. Two reviewers independently screened the literature, and extracted and cross-checked data. The reporting quality of these clinical guidelines was evaluated by using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) , and statistical analysis was carried out with Excel 2017 software.Results:A total of 17 clinical guidelines on skin diseases were included, including 13 Western medicine guidelines and 4 Chinese medicine guidelines. Among the 13 Western medicine guidelines, the number of guidelines reporting the following areas in the RIGHT statement, namely basic information, background, evidence, recommendations, review and quality assurance, funding and declaration and management of interests, and other information, was 9, 6, 0, 4, 0, 1 and 1 respectively; among the 4 Chinese medicine guidelines, the number of guidelines reporting the above 7 areas in the RIGHT statement was 4, 3, 3, 3, 3, 2 and 2 respectively.Conclusion:There is still considerable room for improvement in the overall reporting quality of clinical guidelines on skin diseases published in journals in China during the past 10 years, and the RIGHT statement is recommended for improving the reporting quality in guideline development.

Objective:To evaluate the efficacy of acrivastine alone or in combination with loratadine in the treatment of chronic refractory urticaria.Methods:From March 2017 to December 2018, a multicenter, randomized, controlled clinical study was conducted in 4 centers. Patients with chronic refractory urticaria were randomly divided into two groups, i.e., combined treatment group receiving oral acrivastine capsules 8 mg thrice a day plus oral loratadine tablets 10 mg once a day, and acrivastine alone group receiving oral acrivastine capsules 8 mg thrice a day plus a placebo 10 mg once a day. The course of treatment was 4 weeks. Visits were scheduled at baseline and after 1, 2 and 4 weeks of treatment. At the same time, clinical data were collected, and adverse events were recorded. Symptom scores were evaluated based on degree of itching, number and size of wheals, duration of each attack and number of attacks per week, and symptom score reduce index (SSRI) was used to evaluate the efficacy. Repeated measures analysis of variance and chi-square test were used to evaluate the efficacy and safety.Results:Fifty-three patients in the combined treatment group and 59 in the acrivastine alone group were included in the efficacy analysis. Before treatment, there was no significant difference in symptom score or visual analogue score between the two groups. After 2 weeks of treatment, 19 patients were cured and 10 achieved marked improvement in the combined treatment group, with a response rate of 54.72%; 15 were cured and 6 achieved marked improvement in the acrivastine alone group, with a response rate of 35.59%. After 4 weeks of treatment, 23 patients were cured and 9 achieved marked improvement in the combined treatment group, with a response rate of 60.38%; 20 were cured and 2 achieved marked improvement in the acrivastine alone group, with a response rate of 37.29%. After 2 and 4 weeks of treatment, the response rates were significantly higher in the combined treatment group than in the acrivastine alone group ( χ2 = 4.13, 5.96 respectively, both P < 0.05) . The SSRI significantly differed among different follow-up time points, as well as between the 2 groups ( F = 8.62, 4.38 respectively, both P < 0.05) . Multivariate analysis of variance showed that SSRI was significantly higher in the combined treatment group (0.63 ± 0.05, 0.68 ± 0.05, respectively) than in the acrivastine alone group (0.47 ± 0.05, 0.51 ± 0.05, respectively) after 2 and 4 weeks of treatment (both P < 0.05) . Drug-related adverse reactions, including drowsiness, stomach upsets, headache and liver function abnormality, occurred in 7 patients in the combined treatment group, as well as in 3 in the acrivastine alone group. Conclusion:Acrivastine is safe and effective for the treatment of chronic refractory urticaria, and acrivastine combined with loratadine can markedly improve the efficacy.

Objective:To screen and evaluate sunscreen cosmetics for sensitive facial skin.Methods:From June to August in 2019, 40 subjects with positive lactic acid sting test were recruited from the staff of Chongqing Traditional Chinese Medicine Hospital, and subjected to human skin closed patch testing with 4 kinds of sunscreen cosmetics for sensitive skin (marked as products Ⅰ, Ⅱ, Ⅲ, Ⅳ respectively) separately. Then, the 40 subjects were equally divided into 2 groups to apply 2 sunscreen products with relatively higher safety (according to the above closed patch testing results) on the face respectively. Erythema, edema and desquamation were evaluated at baseline, 2 and 4 weeks after application of the 2 products, and non-invasive measurement methods were used to detect transepidermal water loss (TEWL) , stratum corneum hydration, skin melanin content and skin sebum content. In additon, the 2 products were applied on the back of the subjects separately, and an ultraviolet solar simulator was used to determine the sun protection factor (SPF, n = 12) and protection factor of UVA (PFA, n = 11) . Measurement data were compared using paired t test and one-way analysis of variance, and nonparametric data were compared using Wilcoxon signed rank test. Results:Patch testing showed that only 1 subject developed a grade 1 reaction to the sunscreen product Ⅲ, no subjects showed positive reactions to the product Ⅳ, and the safety of products Ⅲ and Ⅳ was higher than that of the other 2 products. Subjective safety evaluation revealed that the degree of erythema after 4-week application of products Ⅲ and Ⅳ was significantly lower than that before application (Wilcoxon signed rank test, Z = 4.73, 4.82 respectively, both P < 0.05) . Objective efficacy evaluation revealed that the TEWL, stratum corneum hydration and skin melanin content significantly differed among different time points (baseline, after 2- and 4-week application of products Ⅲ and Ⅳ, all P < 0.05); after 4-week application of products Ⅲ and Ⅳ, the TEWL (30.05 ± 1.47, 30.37 ± 1.28 respectively) and skin melanin content (112.58 ± 7.34, 103.47 ± 5.48 respectively) were significantly lower than those before application (all P < 0.05) , and the stratum corneum hydration (62.35 ± 2.67, 63.72 ± 2.54 respectively) was significantly higher than that before application (both P < 0.05) . At week 4, the skin melanin content was significantly lower in the product Ⅳ group (103.47 ± 5.48) than in the product Ⅲ group (112.58 ± 7.34, t = 8.45, P < 0.05) . The SPF and PFA values of the product Ⅳ (51.8 ± 2.9, 10.1 ± 1.2 respectively) were both significantly higher than those of the product Ⅲ (31.5 ± 2.6, 7.4 ± 0.7, t = 15.34, 24.66, respectively, both P < 0.05) . Conclusion:Comprehensive application of closed patch testing, long-term application test and sun protection index determination can be used to screen and evaluate the safety and efficacy of sunscreen cosmetics for sensitive facial skin.

Objective:To analyze clinical characteristics of cosmetics-related adverse reactions and main allergenic components of cosmetics, to provide guidance for cosmetics-related adverse reaction monitoring, and to provide an objective basis for risk assessment.Methods:A total of 512 patients with suspected cosmetic adverse reactions were collected from the outpatient clinic of Chongqing Traditional Chinese Medicine Hospital from March 2018 to October 2019, including 14 males and 498 females. A uniform cosmetic adverse reaction report card was filled in, and medical history of patients and related information about the used cosmetics were recorded; 103 patients (3 males and 100 females) were subjected to patch test with their own cosmetics or cosmetic ingredients, and 48- and 72-hour patch test results were combined for comprehensive determination and analysis.Results:Among the 512 cases of suspected cosmetic adverse reactions, contact dermatitis (495 cases, 96.7%) was the most common manifestation. Cosmetic adverse reactions mainly manifested as erythema (501 cases, 97.9%), papules (313, 61.1%), edema (249, 48.6%), and scaling (166, 32.4%) ; main symptoms included itching (480, 93.8%), burning sensation (359, 70.1%), and tense sensation (297, 58.0%). Patch test with cosmetic ingredients showed positive reactions in 71 of 103 cases, and thimerosal was the allergen mostly liable to cause adverse reactions (31 cases, 30.1%), followed by sodium dodecyl sulfate (29 cases, 28.2%), Peru balsam (17 cases, 16.5%), bronopol (12 cases, 11.7%) and triethanoamine (10 cases, 9.7%). The cosmetic allergens were divided into 14 categories, and the top 4 categories with high positive patch test rates were emulsifiers (54 cases, 45.8%), preservatives (47 cases, 39.8%), fragrances (17 cases, 14.4%) and surfactants (10 cases, 8.5%). Positive patch test reactions were observed in 2 males and 69 females, and there was no significant difference in the positive rate between males and females (2/3 vs. 69/100, χ2 = 0.01, P > 0.05) ; there was also no significant difference in the positive rate among the groups aged 18 - 29 years (34%), 30 - 49 years (34%) and 50 - 70 years (32.4%; χ2 = 0.693, P > 0.05) . Conclusions:Contact dermatitis is the most common adverse reaction to cosmetics. Among the diverse allergenic components of cosmetics, thimerosal is the allergen that is mostly liable to cause adverse reactions, followed by sodium dodecyl sulfate, Peru balsam, bronopol and triethanoamine.

Objective:To determine the expression of the E2F6 transcription factor in human malignant melanoma tissues and cell lines, and to evaluate the effect of E2F6 on proliferation, migration and invasion of a malignant melanoma cell line A375.Methods:Frozen tissues and paraffin-embedded tissue sections were collected from 50 cases of cutaneous malignant melanoma and 30 cases of pigmented nevus in Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital from January 2012 to December 2017. Quantitative reverse transcription-PCR (qRT-PCR) was performed to determine the mRNA expression of E2F6 in the malignant melanoma and pigmented nevus tissues, as well as in 7 malignant melanoma cell lines (HM, A375, WM451, WM35, SK-MEL-1, Hs-695T and MDA-MB-435s) and pigmented nevus cells, and immunohistochemical study and Western blot analysis were conducted to determine the protein expression of E2F6 and β-catenin in the malignant melanoma tissues. An E2F6-inhibiting plasmid and a control plasmid were separately transfected into A375 cells by using a liposome-mediated transfection method, and the E2F6 gene-knockdown efficiency was verified by qRT-PCR and Western blot analysis. Cell counting kit-8 (CCK8) assay, soft-agar plate cloning assay, Transwell migration and invasion assays and 3D cell culture assay were conducted to evaluate the effect of E2F6 gene knockdown on the proliferation, migration and invasion of A375 cells, flow cytometry was performed to detect the cell cycle and apoptosis rate, and Western blot analysis was conducted to determine the protein expression of total β-catenin, activated β-catenin, c-Myc and cyclin D1. The comparison between two groups was carried out by t test, the comparison among several groups by one-way analysis of variance, and multiple comparisons by least significant difference t test; Pearson correlation coefficient was used to analyze the correlation between E2F6 and β-catenin expression in cutaneous malignant melanoma. Results:The E2F6 mRNA expression was significantly higher in the 7 malignant melanoma cell lines than in the pigmented nevus cells (all P < 0.001). qRT-PCR showed that the relative mRNA expression of E2F6 was significantly higher in the cutaneous malignant melanoma tissues (0.000 55 ± 0.000 17) than in the pigmented nevus tissues (0.000 18 ± 0.000 09, t = 3.22, P < 0.001). Both the immunohistochemical study and Western blot analysis showed significantly increased E2F6 protein expression, but decreased β-catenin protein expression in the cutaneous malignant melanoma tissues compared with the pigmented nevus tissues (all P < 0.001). Correlation analysis showed that E2F6 protein expression was negatively correlated with β-catenin expression in the malignant melanoma tissues (immunohistochemical study: r = -0.56, Western blot analysis: r = -0.63, both P < 0.01). After knockdown of the E2F6 gene in A375 cells, the mRNA and protein expression of E2F6 was significantly lower in the E2F6 inhibition group than in the control group ( t = 3.38, 2.76 respectively, both P < 0.001). CCK8 assay showed that the cellular proliferative ability was significantly lower in the E2F6 inhibition group than in the control group ( t = 4.58, P < 0.01) 48 hours after transfection; soft-agar plate cloning assay showed that the colony-formation ratio was significantly lower in the E2F6 inhibition group than in the control group ( t = 2.26, P < 0.001) ; Transwell migration and invasion assays showed that the number of cells crossing the chamber was significantly lower in the E2F6 inhibition group (165 ± 23, 96 ± 11 respectively) than in the control group (376 ± 22, 315 ± 31, t = 3.14, 2.12, respectively, both P < 0.01) ; 3D cell culture assay showed that the cell morphology markedly changed, and the invasive pseudopodia disappeared in the E2F6 inhibition group. Flow cytometry revealed that the proportion of cells at G0-G1 phase and apoptosis rate were significantly higher in the E2F6 inhibition group than in the control group (both P < 0.001). Western blot analysis showed significantly decreased protein expression of β-catenin, activated β-catenin and its downstream target proteins c-Myc and cyclin D1, but significantly increased protein expression of P21 in the E2F6 inhibition group compared with the control group (all P < 0.001) ; additionally, the E2F6 inhibition group showed significantly decreased protein expression of epithelial-mesenchymal transition-related molecules vimentin and N-cadherin, but significantly increased expression of E-cadherin compared with the control group (all P < 0.001) . Conclusions:The E2F6 transcription factor is highly expressed in malignant melanoma. Knockdown of the E2F6 gene in A375 cells can inhibit cell proliferation, migration and invasion by antagonizing the β-catenin signaling pathway.

A 28-year-old female patient presented with indurated erythema and nodules on the right lower limb for 2 years,with mild itching and pain.Skin examination showed a well-circumscribed irregular dark red patch measuring about 10 cm × 5 cm in size on the extensor aspect of the right thigh.On the patch,there were scattered or densely distributed mung bean-to soybean-sized quasi-circular violaceous nodules with a smooth surface,which were hard on palpation.Subcutaneous nodules with medium hardness were found on palpation,and hyperpigmentation was observed on the surface of some nodules.Local skin temperature was increased,with tenderness on palpation.Histopathologically,mononuclear cells showed nodular or sheet-like distribution in the middle and upper dermis,some of which had pale-staining cytoplasm.Moreover,plenty of plasma cells were observed.Immunohistochemistry revealed that histiocytes were stained strongly positive for S100.The number of IgG4-positive plasma cells increased obviously,and was more than 50 per high-power field (× 200).The proportion of IgG4-positive plasma cells in IgG-positive plasma cells was 45％.Finally,the patient was diagnosed with cutaneous Rosai-Dorfman disease with increased IgG4-positive plasma cells.