1.Research progress in hydrogels in tissue engineering trachea
Wenxuan CHEN ; Yibo SHAN ; Fei SUN ; Zhiming SHEN ; Yi LU ; Jianwei ZHU ; Lei YUAN ; Hongcan SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1195-1199
In cases where a tracheal injury exceeds half the length of the adult trachea or one-third of the length of the child trachea, it becomes difficult to perform end-to-end anastomosis after tracheal resection due to excessive tension at the anastomosis site. In such cases, tracheal replacement therapy is required. Advances in tissue engineering technology have led to the development of tissue engineering tracheal substitutes, which have promising applications. Hydrogels, which are highly hydrated and possess a good three-dimensional network structure, biocompatibility, low immunogenicity, biodegradability, and modifiability, have had wide applications in the field of tissue engineering. This article provides a review of the characteristics, advantages, disadvantages, and effects of various hydrogels commonly used in tissue engineering trachea in recent years. Additionally, the article discusses and offers prospects for the future application of hydrogels in the field of tissue engineering trachea.
2.Saltwater stir-fried Plantaginis Semen alleviates renal fibrosis by regulating epithelial-mesenchymal transition in renal tubular cells.
Xin-Lei SHEN ; Qing-Ru ZHU ; Wen-Kai YU ; Li ZHOU ; Qi-Yuan SHAN ; Yi-Hang ZHANG ; Yi-Ni BAO ; Gang CAO
China Journal of Chinese Materia Medica 2025;50(5):1195-1208
This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals
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Epithelial-Mesenchymal Transition/drug effects*
;
Rats, Sprague-Dawley
;
Male
;
Rats
;
Fibrosis/genetics*
;
Drugs, Chinese Herbal/administration & dosage*
;
Kidney Diseases/pathology*
;
Kidney Tubules/pathology*
;
Humans
3.Clinical Characteristics and Prognosis Analysis of Patients with Extranasal NK/T-Cell Lymphoma: A Multicenter Retrospective Study of Huaihai Lymphoma Working Group.
Hui-Rong SHAN ; Qing ZHANG ; Ling WANG ; Yu-Ye SHI ; Yu-Qing MIAO ; Tai-Gang ZHU ; Jing-Jing YE ; Xu-Dong ZHANG ; Liang WANG ; Zi-Yuan SHEN ; Wei SANG
Journal of Experimental Hematology 2025;33(1):93-100
OBJECTIVE:
To explore the clinical characteristics and prognostic factors of patients with extranasal NK/T-cell lymphoma (NKTCL).
METHODS:
The clinical data of 138 patients with NKTCL diagnosed in 10 medical centers of Huaihai Lymphoma Working Group from June 2015 to April 2021 were collected and analyzed retrospectively. The differences in clinicopathological characteristics of patients with different involvement and efficacy of pegaspargase regimen were compared, as well as perform survival analysis.
RESULTS:
A total of 138 extranasal NKTCL patients were included, with a median age of 46 years, and the ratio of males to females was approximately 2∶1. There were 39 patients with gastrointestinal involvement, 32 patients with oropharyngeal involvement, 17 patients with skin involvement, 11 patients with lymph node involvement, 11 patients with orbital involvement, and 28 patients with other parts involvement. Patients with skin involvement had a higher proportion of advanced disease and a lower proportion of CD56 positive rate compared to those with oropharyngeal involvement. Among the patients with gastrointestinal involvement, the survival rate of patients who received pegaspargase regimen was significantly higher than those who were treated without pegaspargase (P < 0.01). Multivariate analysis showed that serum creatinine was an independent prognostic factor for patients with skin involvement ( HR =1.027, 95%CI : 1.001-1.054, P =0.040), ECOG PS and EBV DNA were independent prognostic factors for patients with gastrointestinal involvement ( HR =2.635, 95%CI : 1.096-6.338, P =0.030; HR =4.772, 95% CI : 1.092-20.854, P =0.038), and ECOG PS and CA stage were independent prognostic factors for patients with oropharyngeal involvement ( HR =13.875, 95%CI : 2.517-76.496, P =0.002; HR =20.261, 95%CI : 2.466-166.470, P =0.005).
CONCLUSION
The clinicopathological characteristics of extranasal NKTCL patients with different sites of involvement are vary, and effective individualized treatment need to be further explored.
Adult
;
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
Asparaginase/therapeutic use*
;
Lymphoma, Extranodal NK-T-Cell/pathology*
;
Prognosis
;
Retrospective Studies
;
Survival Rate
;
Polyethylene Glycols
4.A bibliometric analysis of nanoparticles in the treatment of non-small cell lung cancer
Xiangyu XU ; Lei YUAN ; Fei SUN ; Zhiming SHEN ; Yibo SHAN ; Yi LU ; Jianwei ZHU ; Wenxuan CHEN ; Hongcan SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(08):1139-1147
Objective To analyze the current research application status and hotspots of nanoparticles in the treatment of non-small cell lung cancer (NSCLC) and predict the future development trend. Methods The Web of Science database was searched for literatures on nanoparticles use in the treatment of NSCLC from inception to November 2022. CiteSpace, VOSviewer and literature measurement analysis online platform (https://bibliometric.com/) were used for the visual analysis of the number of documents, source journals, authors, organizations, countries and keywords. Results A total of 742 English literatures were included. The results showed that the number of published literatures increased year by year from 2011 and reached the peak in 2020. Researches on nanoparticles and NSCLC treatment were mainly concentrated in China, the United States, India and Japan. China is a major research country in this field, but it lacked cooperation with other countries and related institutions. Among numerous research institutions, the Chinese Academy of Sciences was the authoritative and backbone force in this research field, with the number of published literatures ranking first and the research achievements outstanding. The keyword analysis found that "poly lactic-co-glycolic acid nanoparticles (PLGA NPs)" and "photothermal therapy" had become the latest breakout words since 2018. Moreover, the occurrence frequency of related keywords such as "drug delivery" increased significantly, indicating that the application of PLGA NPs in photothermal therapy might be the current research hotspot and future development trend of NSCLC treatment. Conclusion Currently, the domestic research on the treatment of nanoparticles and NSCLC is in a leading position in the world. The organic combination of nanoparticles with different materials and other NSCLC therapies is expected to improve the prognosis of NSCLC patients. In the future, attempts to develop nanoparticles with different sources and structures and combined with photothermal therapy for the treatment of NSCLC may become a research hotspot of nanoparticles in the treatment of NSCLC.
5.Frontier and hotspot of biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer
Lei YUAN ; Zhiming SHEN ; Fei SUN ; Yibo SHAN ; Yi LU ; Jianwei ZHU ; Hongcan SHI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(04):562-569
Objective To analyze the current development of researches on biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer and to provide reference for subsequent studies. Methods Studies on biomarkers for predicting the efficacy of immunotherapy for non-small cell lung cancer indexed in the Web of Science Core Collection from 2017 to 2021 were searched by computer. The annual distribution, journals, authors, countries, institutions, and keywords of studies were visualized and analyzed by CiteSpace. Results A total of 426 studies were collected, including 298 articles and 128 reviews. The average number of published studies was about 85, and increased year by year. PD-L1 expression, tumor mutational burden, tumor microenvironment and liquid biopsy were hot keywords in this field. Conclusion In the future, combination of biomarkers in the liquid biopsy and tumor microenvironment with radiomics analysis will be the research hotspot and frontier in this field for more accurate assessment with tumor-related signatures such as lymphocytic immune status and characteristics of tumor lesions in non-small cell lung cancer patients.
6.Protective effects of a sunscreen lotion containing Calendula extracts on children′s skin after sun exposure: a single-center, randomized, parallel controlled clinical study
Shan WANG ; Lei JIAO ; Ying LIU ; Mutong ZHAO ; Chunping SHEN ; Yuanyuan XIAO ; Li LI ; Yuan LIANG ; Jing TIAN ; Yang WANG ; Lin MA
Chinese Journal of Dermatology 2024;57(6):562-566
Objective:To investigate the protective effects of a sunscreen lotion containing Calendula extracts on children′s skin against sun exposure, as well as to evaluate its safety and tolerability when applied to children.Methods:A single-center, randomized, split-body/face study was conducted on 200 healthy children aged 3 - < 18 years, who were enrolled from Beijing Children′s Hospital, Capital Medical University from July to August 2022. The participants were randomly and equally divided into Group A (the left side of the body/face topically treated with the test sunscreen, and the right side with the control sunscreen) and Group B (the right side of the body/face topically treated with the test sunscreen, and the left side with the control sunscreen) at a ratio of 1∶1. After applying the sunscreen, they were engaged in outdoor activities under sunlight. Skin tests were conducted on the temporal area, the extensor aspect of the upper arm and forearm before and after sun exposure. The test product was a mild sunscreen lotion containing Calendula extracts with the sun protection factor (SPF) being 50+ and the long-wave ultraviolet protection factor (PA) being +++, and the control product was a baby sunscreen containing licorice extracts (SPF35, PA++). Bilateral differential scales were used to assess clinical symptoms after sun exposure, erythema values to clinically evaluate erythema after sun exposure, and the multifunctional skin testing platform MPA10 to measure melanin and erythema values, stratum corneum hydration, and transepidermal water loss (TEWL) at the tested sites. Related adverse events were observed and recorded during the study. The paired t-test or Wilcoxon signed-rank test was used for the comparison of quantitative data, and chi-square test (Fisher′s exact test) for the comparison of count data. Results:Totally, 198 children completed the study and visits, including 100 males (50.5%) and 98 females (49.5%), aged from 3 to 17 years (8.11 ± 0.23 years), and there were 99 cases each in the Group A and Group B. The numbers of participants with more obvious sunburn symptoms after sun exposure in the 3 tested areas were all higher on the control side than on the test side (the temporal area: 11 cases vs. 4 cases; the extensor aspect of the upper arm: 16 cases vs. 2 cases; the extensor aspect of the forearm: 33 cases vs. 3 cases), with significant differences between the bilateral sides (all P<0.001). No significant differences were observed in the erythema values between the test side and control side in the 3 tested areas (all P > 0.05). In the extensor aspect of the upper arm and forearm, the difference in the melanin value before and after sun exposure was significantly smaller on the test side (3.57 ± 2.41, 1.74 ± 1.68, respectively) than on the control side (9.50 ± 2.21, 8.13 ± 1.87, respectively, both P < 0.001) ; in the temporal region and the extensor aspect of the upper arm and forearm, the difference in the stratum corneum hydration level before and after sun exposure was significantly greater on the test side (7.72[-2.19, 19.44], 9.56 ± 1.37, 9.05 ± 1.37, respectively) than on the control side (-3.25[-13.54, 9.94], 3.63 ± 1.32, 3.73 ± 1.31, respectively, all P < 0.001) in the temporal region and the extensor aspect of the upper arm and forearm. However, there were no significant differences in the changes in the erythema or TEWL values before and after sun exposure between the test side and control side in either of the 3 tested areas (all P > 0.05). During this study, 1 case (0.51%) experienced transient urticaria on the control side, and no serious adverse events occurred. Conclusion:The mild sunscreen lotion containing Calendula extracts demonstrated superior efficacy to the control product in improving skin symptoms after sun exposure such as hyperpigmentation among healthy children aged 3 - < 18 years, with good tolerability and a relatively low incidence of adverse reactions.
7.Analysis of clinical characteristics and treatment status of atopic dermatitis in a children's hospital in Beijing from 2015 to 2019.
Chun Ping SHEN ; Yuan LIANG ; Ying LIU ; Lei JIAO ; Jing TIAN ; Yang WANG ; Shan WANG ; Mu Tong ZHAO ; Nan DANG ; Lin MA
Chinese Journal of Preventive Medicine 2023;57(11):1848-1854
To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ2=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ2=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.
Humans
;
Child
;
Male
;
Female
;
Infant, Newborn
;
Infant
;
Child, Preschool
;
Adolescent
;
Dermatitis, Atopic/psychology*
;
Cross-Sectional Studies
;
Retrospective Studies
;
Severity of Illness Index
;
Hospitals
;
Quality of Life
8.Analysis of clinical characteristics and treatment status of atopic dermatitis in a children's hospital in Beijing from 2015 to 2019.
Chun Ping SHEN ; Yuan LIANG ; Ying LIU ; Lei JIAO ; Jing TIAN ; Yang WANG ; Shan WANG ; Mu Tong ZHAO ; Nan DANG ; Lin MA
Chinese Journal of Preventive Medicine 2023;57(11):1848-1854
To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ2=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ2=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.
Humans
;
Child
;
Male
;
Female
;
Infant, Newborn
;
Infant
;
Child, Preschool
;
Adolescent
;
Dermatitis, Atopic/psychology*
;
Cross-Sectional Studies
;
Retrospective Studies
;
Severity of Illness Index
;
Hospitals
;
Quality of Life
9.Efficacy of daily use of a test emollient combined with topical glucocorticoids applied at the weekend for delaying the recurrence of atopic dermatitis in children during the maintenance period: a randomized, blank-controlled, multicenter clinical study
Chunping SHEN ; Ping LI ; Xiaoyan LUO ; Yuan LIANG ; Ying LIU ; Mutong ZHAO ; Shan WANG ; Jing TIAN ; Lei JIAO ; Yang WANG ; Zhen LUO ; Shijuan YU ; Xiao FANG ; Hua WANG ; Lin MA
Chinese Journal of Dermatology 2023;56(8):756-762
Objective:To evaluate the efficacy of daily use of a test emollient combined with topical glucocorticoids applied at the weekend for delaying the recurrence of atopic dermatitis (AD) in children during the maintenance period.Methods:A randomized, blank-controlled, multicenter clinical study was conducted in children with moderate AD from Beijing Children′s Hospital, Capital Medical University, Children′s Hospital of Chongqing Medical University and Shenzhen Children′s Hospital from March 2021 to February 2022. A total of 127 children aged 0 - 12 years with moderate AD were treated with topical glucocorticoids combined with emollients during the run-in period, 112 out of them achieved the investigator′s global assessment (IGA) score ≤ 1 point, and then the 112 patients were randomly divided into a test group (56 cases) and a control group (56 cases) at a ratio of 1∶1. Patients in the test group received treatment with a test emollient twice a day in combination with topical glucocorticoids applied at the weekend, and those in the control group were only treated with topical glucocorticoids at the weekend. Patients in the two groups were followed up at baseline, week 2 (± 3 d), week 4 (± 5 d), and week 12 (±7 d), as well as at the time of AD relapse, and the effect of the test emollient on the remission rate of AD in children during the maintenance period was evaluated, so were its effects on the dosage of topical glucocorticoids, pruritus, sleep, and skin pH. The occurrence of treatment-related adverse events was evaluated and recorded at the same time. Study endpoints were defined as AD relapse during the maintenance period, end of 12-week follow-up, or occurrence of serious adverse events. Comparisons of efficacy indicators between groups were conducted by using chi-square test, Kaplan-Meier survival analysis, Satterthwaite t′ test and Mann-Whitney U test. Results:In the full-analysis set, 45 (80.36%) patients with AD maintained remission in the test group (56 cases) and 30 (53.57%) in the control group (56 cases), and the remission rate difference between the two groups was 26.79% (95% confidence interval [ CI]: 10.09%, 43.49%; χ2 = 9.11, P = 0.003) ; the 12-week follow-up during the maintenance period showed that the time to first relapse was 75.05 ± 25.07 days in the test group, which was significantly longer than that in the control group (49.55 ± 33.92 days, t′ = 4.52, P < 0.001). At the study endpoint, the test group showed significantly decreased AD disease severity score (eczema area and severity index [EASI] score: 0.00 [0.00, 1.20] points vs. 0.60 [0.00, 4.00] points), pruritus visual analog scale (VAS) score (0.00 [0.00, 2.00] points vs. 2. 00 [0.00, 10.00] points), and sleep VAS score (0.00 [0.00, 0.00] points vs. 1.00 [0.00, 4.00] points) compared with the control group ( Z = -2.77, 2.43, 3.48, P = 0.006, = 0.015, < 0.001, respectively), while there was no significant difference in the pH value at the lesional sites between the test group and control group ( t = 0.97, P = 0.335). For the group aged 0 - 2 years, the average daily glucocorticoid dosage at the weekend in AD children during the maintenance period was significantly lower in the test group than in the control group ( Z = -1.97, P = 0.049) ; for the group aged >2 - 12 years, there was no significant difference in the average daily glucocorticoid dosage at the weekend between the two groups ( Z = -0.25, P = 0.802). During the study period, no significant difference was observed in the incidence of treatment-related adverse events between the test group (2/56, 3.57%) and control group (3/56, 5.36%; P = 1.000), and no serious adverse events occurred. Conclusion:Compared with the weekend treatment with topical glucocorticoids alone, the daily use of the test emollient combined with topical glucocorticoids at the weekend could markedly improve the remission rate of AD, prolong the time to relapse, and reduce the disease severity at relapse in children with AD during the maintenance period, which provides a new option for maintenance treatment of children with AD.
10.Efficacy of crisaborole ointment in clinical symptom relief in the early stage of childhood atopic dermatitis and in symptom improvement in the remission stage: a multicenter clinical study
Shan WANG ; Xingyu WANG ; Hong SHU ; Bin ZHANG ; Hang SHI ; Huan YANG ; Qiufang QIAN ; Hongyan MA ; Yuan LIANG ; Mutong ZHAO ; Chunping SHEN ; Lei JIAO ; Jing TIAN ; Yang WANG ; Ying GU ; Jing SUN ; Ying LIU ; Ping LI ; Hua WANG ; Lin MA
Chinese Journal of Dermatology 2023;56(9):815-821
Objective:To evaluate the efficacy and tolerability of crisaborole 2% ointment in the treatment of childhood atopic dermatitis (AD) at the early stage, and to compare the efficacy of every-other-day (Qod) regimen versus twice-a-week (Biw) regimen against recurrence in the remission stage of AD.Methods:A multicenter, randomized, open-label clinical trial was conducted. Totally, 150 children with mild to moderate AD aged 2 - < 18 years were enrolled from 6 hospitals (including Beijing Children′s Hospital, Capital Medical University, etc), and randomly divided into the Qod group (76 cases) and the Biw group (74 cases). In the acute stage of AD, both groups were treated with topical crisaborole 2% ointment on skin lesions twice a day for 2 - 4 weeks, as well as with emollients throughout the whole body. The improvement of early clinical symptoms was evaluated, and the occurrence of adverse reactions was recorded in the follow up. Once the investigator′s static global assessment (ISGA) scores decreased to 1 point or less, the patient would be enrolled into the remission stage. In the remission stage of AD, patients in the Qod group and Biw group were treated with crisaborole ointment every other day and twice a week respectively; the recurrence rate of AD in the remission stage was evaluated, as well as the severity of skin lesions, itching, life quality, and the occurrence of adverse reactions at weeks 4, 8, and 12. Statistical analysis was carried out with SPSS 23.0 software by using t test for comparisons of normally distributed continuous data between two groups, Mann-Whitney U test for non-normally distributed data, chi-square test for enumeration data, and Kaplan-Meier method for analysis of survival rates. Results:A total of 142 patients were enrolled in the modified intention-to-treat population, including 71 in the Qod group and 71 in the Biw group. In the acute stage of AD, the improvement of itching and skin lesions self-reported by the children or their family members occurred on days 1.9 (1.0, 3.0) and 2.0 (1.0, 4.1) after the application of crisaborole ointment, respectively. At the end of treatment in the acute stage, 89 children (62.7%) achieved ISGA 0/1 and successfully transferred into the remission stage. The follow-up in the remission stage was completed in 83 patients (44 in the Qod group and 39 in the Biw group). In addition, recurrence occurred in 19 (43.2%) and 12 (30.8%) patients in the Qod group and Biw group respectively, and there was no significant difference in the recurrence rate between the two groups ( χ2 = 1.36, P = 0.243) ; the average time to recurrence was 64.25 (95% CI: 53.33 - 75.17) days and 75.78 (95% CI: 65.46 - 86.10) days in the Qod group and Biw group respectively. Among the patients who were in the remission stage and had not yet experienced relapse at weeks 4, 8, and 12, there were no significant differences in the eczema area and severity index (EASI) scores, ISGA scores, pruritus numerical rating scale (NRS) scores, or quality-of-life scores between the two groups (all P > 0.05) at any time points, except for the ISGA scores at week 12 (Biw group: 0 [0, 1] point vs. Qod group: 1 [0, 1] point; Z = -2.31, P = 0.021). A total of 146 patients were enrolled in the safety set. During the study period, 70 adverse events occurred in 65 patients, with an incidence rate of 44.5%, and all were mild or moderate adverse events; 55 (37.7%) patients experienced discomfort at the medication site, which mainly referred to pain (45 cases, 30.8%) and mostly occurred in the tender and skinfold areas. Conclusions:Crisaborole 2% ointment could effectively relieve clinical symptoms in children with mild to moderate AD in the early stage, and intermittent treatment could continuously relieve clinical symptoms in the remission stage. The common adverse reaction was discomfort at the application site in the early stage of AD. There was no significant difference in the impact on AD recurrence in the remission stage between the Qod regimen and Biw regimen.

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