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.

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.

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.

OBJECTIVE To investigate the antibacterial activities of flavaspidic acid BB against the main pathogens of skin and soft tissue infections such as methicillin -resistant Staphylococcus aureus （MRSA）and methicillin -sensitive Staphylococcus aureus （MSSA） in vitro and in vivo . METHODS Microdilution method was used to determine the minimum inhibitory concentration（MIC）and minimum bactericidal concentration （MBC）of flavaspidic acid BB on 10 strains of MRSA and 13 strains of MSSA ；time-kill curves of MRSA 11 and MSSA 23 strains were drawn by plate method ；the checkerboard dilution method was used to determine the combined antibacterial effect of flavaspidic acid BB and mupirocin ；the skin abscess model of mice was established to evaluate the antibacterial effects of 0.5%，1%，2% flavaspidic acid BB cream on MRSA 11 or MSSA 23 strains in vivo；scanning electron microscopy was used to observe the effects of flavaspidic acid BB on the morphology of MRSA 11 or MSSA23 strains. The contents of nucleic acid leakage and extracellular protein were also determined . RESULTS MIC and MBC ranges of flavaspidic acid BB against 10 strains of MRSA were 6.30-80.00 μg/mL and 40.00-640.00 μg/mL；MIC and MBC ranges of 13 strains of MSSA were 40.00-80.00 μg/mL and 63.50-126.99 μg/mL，respectively. The bactericidal rate of MRSA 11 and MSSA23 strains were 99.9% after interfered with plavaspidic acid BB for 36 h. The combination of flavaspidic acid BB and mupirocin showed an additive effect on MRSA strain and an additive or synergistic effect on MSSA strain . The 0.5%，1% and 2% flavaspidic acid BB cream could reduce the volume of abscess and the bacterial load of skin abscess model mice to some extent （P＜0.05），and improved the pathological changes of skin inflammation in skin abscess site of mice . Flavaspidic acid BB could make MRSA 11 and MSSA 23 cells shrinkage and rupture ，and significantly increase the contents of nucleic acid leakage and extracellular protein （P＜0.01）. CONCLUSIONS Flavaspidicacid BB shows good antibacterial effect on MRSA and MSSAE-mail：tchp66@163.com in vitro and in vivo ，the mechanism of which may be related to the change of membrane permeability .

OBJECTIVE To study the effects of yunaconitine on myocardial injury in rats and its mechanism related to mitochondrial apoptosis pathway rats. METHODS Forty SD rats were divided into normal group （normal saline）， yunaconitine high-dose and low-dose groups（0.14， 0.09 mg/kg）and aconitine group （positive control， 0.88 mg/kg） by random number method， with 10 rats in each group. They were given relevant medicine intragastrically， once a day， for consecutive 7 days. The levels of lactate dehydrogenase （LDH）， creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， superoxide dismutase （SOD） and malondialdehyde （MDA） in serum as well as the level of reactive oxygen species （ROS） in myocardial tissue were detected. The pathomorphological changes of myocardium and ultrastructural changes of myocardial mitochondria were all observed. The apoptosis of cardiomyocytes was determined. The protein relative expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 were determined in myocardium of rats. RESULTS Compared with normal group， the serum levels of LDH， CK， CK-MB and MDA， the apoptotic numbers of cardiomyocytes， the level of ROS and protein expression of caspase-3 in myocardium were increased significantly in yunaconitine high-dose and low- dose groups （P＜0.05 or P＜0.01）； serum level of SOD and Bcl-2/Bax ratio in myocardium were all decreased significantly （P＜ 0.01）； the protein relative expressions of caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 in myocardium were significantly increased in yunaconitine high-dose group （P＜0.05）； some pathomorphological changes were found in 2 groups， such as myocardial fiber disorder， mitochondrial swelling. CONCLUSIONS Yunacotine could cause myocardial injury in rats. Its mechanism might be related to destroying the integrity of cardiomyocyte membrane， causing oxidative stress of cardiomyocyte， and inducing the apoptosis of myocardial cells through mitochondrial pathway.

Objective:To investigate short-term efficacy and safety of subcutaneous injection of dupilumab in the treatment of moderate-to-severe childhood atopic dermatitis (AD) .Methods:A retrospective study was conducted on clinical data from children who were diagnosed with moderate-to-severe AD and subcutaneously injected with dupilumab in Department of Dermatology, Beijing Children′s Hospital, Capital Medical University from March 2021 to August 2021. Changes in the Eczema Area and Severity Index (EASI), itch Numeric Rating Scale (NRS) score, SCORing Atopic Dermatitis (SCORAD) index, and Dermatology Family quality of life Index (DFI) were analyzed before and 4 weeks after the first subcutaneous injection of dupilumab. Adverse events were collected during the first injection to the first follow-up visit at week 4 after the start of treatment. Normally distributed measurement indices were compared by using paired t test, non-normally distributed measurement indices were compared by using signed rank test, and logistic regression analysis was used to evaluate the effects of disease duration, eosinophil counts, IgE levels, personal and family history of allergic diseases on EASI50 (≥ 50% decrease in the EASI score) after dupilumab treatment. Results:A total of 39 children were enrolled in this study, including 21 males and 18 females. Twenty-one patients were aged 2 to < 6 years, 18 were aged 6 to < 18 years, and their median age ( Q1, Q3) was 65.0 (53.0, 111.0) months. Four weeks after the single-dose subcutaneous injection of dupilumab, 18 patients (84.85%) achieved ≥ 50% decrease in EASI score, 13 (60.61%) ≥ 75% decrease in EASI score; 18 (75.76%) experienced a decrease of ≥ 4 points in peak NRS, and 20 (81.82%) ≥ 3 points in peak NRS; the SCORAD score decreased by ≥ 50% in 15 (68.75%) patients, and by ≥ 75% in 7 (18.75%). Neither common adverse events such as conjunctivitis, skin infections, injection site reactions, nor serious adverse events were observed in any of the children from the first injection to the first follow-up visit at week 4. Logistic regression analysis showed no significant effect of the disease duration, eosinophil counts, IgE levels, personal or family history of allergic diseases on EASI50 (all P > 0.05) . Conclusion:A single-dose subcutaneous injection of dupilumab can markedly improve pruritus and severity of skin lesions in children with moderate-to-severe AD, and enhance the family quality of life, with favorable short-term safety.

Objective:To explore the value of Care Evaluation Scale (CES) in cancer patients for predicting survival time in patients with advanced breast cancer.Methods:From November 2018 to June 2020, the convenient sampling was used to select 140 patients with advanced breast cancer who were treated in Qingdao Central Hospital Affiliated to Qingdao University and 140 home caregivers as the research objects. Researchers contacted home caregivers of patients with advanced breast cancer to set up a time and place to conduct one-on-one surveys of research objects using the Cancer Patient CES. Pearson correlation was used to analyze the correlation between survival time and CES score in patients with advanced breast cancer. Multiple stepwise regression analysis was used to analyze the influencing factors of CES scores in patients with advanced breast cancer. A total of 140 questionnaires were distributed, of which 133 were valid, and the effective recovery rate was 95.00% (133/140) .Results:Among the 133 patients with advanced breast cancer, 76 were Luminal A, 19 were Luminal B, 12 were ERBB 2+ and 26 were Basal-like. Luminal type A advanced breast cancer patients had the longest survival time, and the differences were statistically significant compared with those of ERBB 2+ and Basal-like advanced breast cancer patients ( P<0.05) . There was no statistically significant difference in survival time between Luminal B type advanced breast cancer and Luminal A, ERBB 2+ and Basal-like advanced breast cancer patients ( P>0.05) . Luminal type A advanced breast cancer patients had the highest CES score, and the differences were statistically significant compared with those of Luminal type B, ERBB 2+ and Basal-like advanced breast cancer patients ( P<0.05) . There was no statistically significant difference in the CES score between Luminal B advanced breast cancer and Luminal A, ERBB 2+ and Basal-like advanced breast cancer ( P>0.05) . Pearson correlation analysis found that the survival time of patients with advanced breast cancer was positively correlated with the CES score ( r=0.892, P<0.05) . The influencing factors of CES empowerment in patients with advanced breast cancer included physical care provided by doctors, mental health care, environment, explanation or instructions by doctors to family members, collaboration and persistence, consideration for family members, availability, cost, explanation or instructions by doctors to patients and physical care provided by nurses. Conclusions:CES in cancer patients can effectively predict the survival time of patients with advanced breast cancer. The molecular types of patients with advanced breast cancer are different and the effect of predicting survival time is also different.

OBJECTIVE：To study the effect of isofla vaspidicacid PB （called PB for short ）on the biofilm adhesion and the gene expression of ergosterol metabolism related enzymes in Trichophyton rubrum . METHODS ：M38-A2 method was adopted to determine MIC of PB to T. rubrum . MTT assay was used to screen the biolfilm condition and initial adhesion period of T. rubrum . The effects of different concentrations of PB （40，80，160 µg/mL）on the adhesion duration of T. rubrum （growth control group without PB was set up ，similarly hereinafter ）were evaluated and the adhesion rate was calculated by using XTT assay ；the effects of different concentrations of PB （20，40，80 µg/mL）on the biofilm formation of T. rubrum at different initial adhesion periods （3，5，9 h）were observed and the adhesion rate was calculated by using XTT assay combined with inverted microscope ；qRT-PCR method was used to detect the effects of PB （320 µg/mL）on the mRNA expression of ergosterol metabolism related enzyme gene ERG6 and ERG11 in biofilm of T. rubrum . RESULTS ：MIC of PB to T. rubrum was 20 µg/mL. The biofilm of T. rubrum in RPMI-1640 medium containing 10％ FBS was the most metabolism activity at 6 h of initial adhesion. Compared with growth control group ，after treated with different concentrations of PB ，adhesion rate and mRNA expression of ERG6 and ERG11 in biofilm were decreased significantly （P＜0.01）. Hyphae decreased or even disappeared ，and the adhesion inhibition rate （at 5 and 9 h of initial adhesion ）increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：PB can inhibit the adhesion of T. rubrum and reduce the hyphae ；the mechanism may be associated with the inhibition of the biofilm adhesion and mRNA expression of ergosterol metabolism related enzyme gene ERG6 and ERG11.

OBJECTIVE：To study the toxicity mechanism of yunacotine-induced arrhythmia in rats. METHODS ：Totally 32 rats were randomly divided by random number table method into normal control group ，yunacotine low-dose and high-dose groups （0.09，0.14 mg/kg），aconitine group （positive control ，0.88 mg/kg），with 8 rats in each group. Administration groups were given the corresponding drugs once a day ，and normal control group was given the constant volume of normal saline ，for consecutive 7 d. After last intragastric administration ，the changes of electrocardiogram （ECG） were observed. The contents of adenosine triphosphate（ATP）in myocardial tissue and Ca 2+ in myocardial cells ，the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase as well as the protein expression of ranolidine receptor 2（RyR2）and Ca 2+-ATPase（SERCA2）in myocardial tissue were determined. RESULTS：Compared with normal control group ，time limit of QRS wave and QTc intervals of rats were prolonged significantly in yunaconitine low-dose group （P＜0.01）. The content of Ca 2 + in myocardial cells ， the ATP contents ， the activities of Ca2+-Mg2+-ATPase and Na +-K+-ATPase as well as the protein expression of SERCA 2 in myocardial tissue were reduced significantly （P＜0.05 or P＜0.01）. The heart rate of rats in yunaconitine high-dose group and aconitine group were increased significantly （P＜ 0.05 or P＜0.01），and time limit of QRS wave and QTc intervals were significantly prolonged （P＜0.01）；the content of Ca 2+ in myocardial cells was increased significantly （P＜0.01）；ATP content ，the activities of Ca 2+-Mg2+-ATPase and Na +-K+-ATPase，and protein expression of RyR 2 and SERCA 2 in myocardial tissue were decreased significantly （P＜0.01）. CONCLUSIONS ： Yunaconitine can induce arrhythmia in rats ，the mechanism of which may be associated with Ca 2+ overload that resulted from reducing the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase and down-regulating the expression of related calcium transporter RyR2 and SERCA 2.

OBJECTIVE：To study the effects of different penetration enhancers on in vitro transdermal permeation of Flavaspidic acid BB cream. METHODS ：Flavaspidic acid BB cream was prepared ，containing 11 kinds of different penetration enhancers as 1％ azone，2％ azone，3％ azone，4％ azone，1％ menthol，1％ propylene glycol ，1％ oleic acid ，1％ azone+1％ menthol，1％ azone+1％ propanediol，1％ azone+1％ oleic acid or 1％ menthol+1％ propanediol. Modified Franz diffusion cell was adopted using abdominal skin of isolated male rat as transdermal barrier. The content of flavaspidic acid BB was determined by UPLC. The accumulative transdermal amount （Q24 h）and percutaneous permeability （Jss）within 24 h were calculated ；and compared with Flavaspidic acid BB cream without transdermal enhancer ，the enhancement ratio （ER）was calculated. RESULTS ： Q24 h of Flavaspidic acid BB cream with above 11 kinds of transdermal enhancers were （82.96±7.15），（80.17±0.66），（78.22± 1.87），（73.53±1.24），（35.65±2.23），（34.02±1.73），（42.68±2.66），（33.94±1.37），（34.16±1.54），（46.78±1.21），（43.66±1.69） μg/cm2，respectively. Jss value were （5.26±0.10），（4.69±0.12），（4.45±0.45），（4.00±0.06），（3.74±0.33），（3.23±0.18）， （3.73±0.53），（3.14±0.47），（3.54±0.11），（3.98±0.34），（4.34±0.14）μg（/ cm2·h），respectively. ER were 2.055，1.831，1.738， 1.564，1.462，1.263，1.456，1.227，1.385，1.557，1.698，respectively. CONCLUSIONS ：All of the above transdermal absorption enhancers can enhance the percutaneous absorption of Flavaspidic acid BB cream ，among which ，1％ azone is the best.