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BACKGROUND@#Psoriasis is a common chronic inflammatory skin disease with 2% to 3% prevalence worldwide and a heavy social-psychological burden for patients and their families. As the exact pathogenesis of psoriasis is still unknown, the current treatment is far from satisfactory. Thus, there is an urgent need to find a more effective therapy for this disease. Keratin 17 (K17), a type I intermediate filament, is overexpressed in the psoriatic epidermis and plays a critical pathogenic role by stimulating T cells in psoriasis. Therefore, we hypothesized that inhibiting K17 may be a potential therapeutic approach for psoriasis. This study aimed to investigate the therapeutic effect of K17-specific small interfering RNA (siRNA) on mice with imiquimod (IMQ)-induced psoriasis-like dermatitis.@*METHODS@#Eight-week-old female BALB/c mice were administered a 5% IMQ cream on both ears to produce psoriatic dermatitis. On day 3, K17 siRNA was mixed with an emulsion matrix and applied topically to the left ears of the mice after IMQ application every day for 7 days. The right ears of the mice were treated in parallel with negative control (NC) siRNA. Inflammation was evaluated by gross ear thickness, histopathology, the infiltration of inflammatory cells (CD3+ T cells and neutrophils) using immunofluorescence, and the expression of cytokine production using real-time quantitative polymerase chain reaction. The obtained data were statistically evaluated by unpaired t-tests and a one-way analysis of variance.@*RESULTS@#The severity of IMQ-induced dermatitis on K17 siRNA-treated mice ears was significantly lower than that on NC siRNA-treated mice ears, as evidenced by the alleviated ear inflammation phenotype, including decreased ear thickness, infiltration of inflammatory cells (CD3+ T cells and neutrophils), and inflammatory cytokine/chemokine expression levels (interleukin 17 [IL-17], IL-22, IL-23, C-X-C motif chemokine ligand 1, and C-C motif chemokine ligand 20) (P < 0.05 vs. the Blank or NC siRNA groups). Compared to the NC siRNA treatment, the K17 siRNA treatment resulted in increased K1 and K10 expression, which are characteristic of keratinocyte differentiation (vs. NC siRNA, K17 siRNA1 group: K1, t = 4.782, P = 0.0050; K10, t = 3.365, P = 0.0120; K17 siRNA2 group: K1, t = 4.104, P = 0.0093; K10, t = 4.168, P = 0.0042; siRNA Mix group: K1, t = 3.065, P = 0.0221; K10, t = 10.83, P < 0.0001), and decreased K16 expression, which is characteristic of keratinocyte proliferation (vs. NC siRNA, K17 siRNA1 group: t = 4.156, P = 0.0043; K17 siRNA2 group: t = 2.834, P = 0.0253; siRNA Mix group: t = 2.734, P = 0.0250).@*CONCLUSIONS@#Inhibition of K17 expression by its specific siRNA significantly alleviated inflammation in mice with IMQ-induced psoriasis-like dermatitis. Thus, gene therapy targeting K17 may be a potential treatment approach for psoriasis.
Subject(s)
Animals , Female , Humans , Mice , Dermatitis , Disease Models, Animal , Imiquimod , Inflammation , Keratin-17/genetics , Mice, Inbred BALB C , Psoriasis/genetics , RNA, Small Interfering/genetics , SkinABSTRACT
Objective@#To evaluate the actual efficacy of cervical cancer and precancerous lesions screening approaches in real-world regions with different economic levels in China.@*Methods@#The demonstrative application and effect evaluation of cervical cancer screening program were conducted in 21 hospitals nationwide from 2015 to 2018. Multi-stage sampling method was adopted to divide the country into 7 large areas according to geographical location. Two to four screening sites of two types of cancer (cervical cancer and breast cancer) were selected in each area, and the grassroots screening sites were implemented under the guidance of superior hospitals. In rural areas, women were initially screened using cytology, human papillomavirus (HPV) testing and visual inspection. The women with positive cytology or visual inspection were referred for colposcopy, and the women with positive HPV infection were randomly referred for reflex cytology or visual inspection, or direct colposcopy examination. In urban areas, women were primarily randomized into cytology or HPV testing groups. The women with abnormal cytology or positive HPV 16/18 infection were directly referred for colposcopy examination, whereas the women with positive infection of the other 12 high-risk subtypes of HPV were referred for reflex cytology or colposcopy. All of recruited women would be follow-up and screened by the baseline screening techniques in the third year while the positive women underwent colposcopy examination. The positive rates, referral rates, the detection rates of grade 2 and above of cervical intraepithelial neoplasia (CIN 2+ ) were compared.@*Results@#A total of 63 931 women were recruited at the baseline. Among them, 11 rural sites included 33 823 women: 15 577, 11 157 and 7 089 women were screened by HPV testing, visual inspection via acetic acid or Lugol′s iodine (VIA/VILI) and cytology, respectively. Additionally, 30 108 women were from 10 urban sites: 9 907 and 20 201 women were screened by cytology and HPV subtyping, respectively. The HPV positive rate for urban women was 9.34%, whereas that for rural women was 12.53%. The abnormal rate of cytology for urban women was 5.63%, and that for rural women was 4.24%. The positive rate of VIA/VILI in the rural women was 12.25% Furthermore, the detection rate of CIN2+ at the baseline was 0.56%, and that was statistically higher in HPV-positive group than cytology-positive group (P<0.05).@*Conclusions@#All of screening sites completed the baseline screening tasks as expected. The prevalence of HPV infection is higher in rural women than urban women. The performance of HPV testing is better than cytology for detecting CIN2+ cases. This real-world demonstration study provides evidences for cervical cancer prevention and control in different regions.
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Objective To investigate and explore the awareness and willingness of breast cancer screening between Han and Mongolian women in Ordos, Inner Mongolia Autonomous Region, and to analyze the influence factors. Methods The patients answered investigation questionnaires face to face, and the content of questionnaire included demographic information, breast cancer awareness and relevant affecting factors on the awareness and willingness. Results 11162 (88.2 %) Han women and 1495 (11.8 %) Mongolian women were enrolled in the survey, with the average age of (45.4 ±7.1) years old and (45.4 ±6.8) years old. The education level (high school and above) of Han women was lower than that of Mongolian women [4456 women (40.0%) vs. 750 women (50.2%), χ2= 57.041, P< 0.001]. The Main way to delivery information on breast cancer screening in Han and Mongolian women was from their family members or friends [5002 women (44.9%) vs. 688 women (46.1%),χ2=40.699, P<0.001]. The proportions of never attending screening in the Han and Mongolian women were 41.7 % (4640 women) and 45.9 % (683 women), respectively (χ2=14.075, P=0.001). The breast self-examination rate of Han women were higher than that of Mongolian [71.1 % (7926 women) vs. 58.5 % (872 women), χ2= 98.466, P< 0.001]. According to logistics regression analysis, the cognitive level of women with high education level and breast disease history was higher (all P<0.001). Conclusions The cognitive level of breast cancer screening in Han women is better than that in the Mongolian, however, the overall level are low. It is necessary to strengthen the propaganda and education, and to encourage women to actively participate in breast cancer screening.