Humans ; Adolescent ; Acne Vulgaris/therapy* ; Skin Care ; Surveys and Questionnaires ; Cognition ; China ; Skin

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 evaluate clinical efficacy and safety of topical compound oleum lithospermi in the treatment of mild to moderate diaper dermatitis.Methods:A multicenter, randomized, positive-drug parallel-controlled clinical trial was conducted in 19 hospitals from July 2019 to August 2020. Children aged 0 - 12 months with mild to moderate diaper dermatitis were enrolled and randomly divided into 2 groups using a random number table: test group topically treated with compound oleum lithospermi, and control group topically treated with zinc oxide cream. The treatment was carried out 6 - 8 times a day for 7 days. Visits were scheduled on days 0 and 7, and total response rate and clinical healing time were evaluated. Changes in the dermatitis family impact (DFI) score were compared between the test group and control group, and adverse events were recorded. Statistical analysis was carried out by using independent-sample t test for normally distributed continuous data, Wilcoxon rank sum test for non-normally distributed continuous data, and chi-square test or Fisher′s exact test for unordered categorical data; survival curves were drawn, and log-rank test was used for comparisons between two groups. Results:A total of 343 children with diaper dermatitis were enrolled in this study. Among them, 31 children violated the protocol, so 312 were included in the per protocol set, including 157 in the test group and 155 in the control group, and all completed the visits on days 0 and 7. The total response rate was significantly higher in the test group (87.26%, 137/157) than in the control group (78.71%, 122/155; χ2 = 4.04, P = 0.044) . The clinical healing time was significantly shorter in the test group (5.33 days) than in the control group (6.13 days; χ2 = 4.67, P = 0.025) . After 7-day treatment, the DFI score significantly decreased in both the 2 groups compared with that before the treatment, but there was no significant difference in the DFI score between the 2 groups (test group: 4.02 ± 6.96, control group: 3.58 ± 5.90, Z = -0.39, P = 0.686) . The incidence of adverse events was 2.92% (5/171) and 5.45% (9/165) in the test group and control group respectively, and there was no significant difference between the 2 groups ( χ2 = 0.03, P = 0.865) . Conclusion:Compound oleum lithospermi can markedly reduce the clinical severity of diaper dermatitis, improve the total response rate, shorten the clinical treatment period, and improve the quality of life of children′s families with a favorable safety profile.

OBJECTIVE To prepar e and characterize danazol （DAZ）-sodium caseinate （SC）composite nanoparticles ，and to study the mechanism of preparing nanoparticles in “bottom-up”technology. METHODS SC was used as a stabilizer for regulating nanoparticles，so that DAZ-SC composite nanoparticles were prepared by anti-solvent precipitation method. The particle size ， Zeta-potential，micro-morphology，stability，encapsulation efficiency ，drug loading and in vitro dissolution rate were characterized. Fluorescence spectra ，IR spectra ，FBRM and other methods were used to analyze the interaction mechanism between DAZ and SC. RESULTS The particle size of DAZ-SC composite nanoparticles was （223.7±12.5）nm，and the polydispersity index was 0.274± 0.012. Zeta-potential was －（17.81±1.63）mV（n＝3）. The stability of nano-suspension was good ，the solid properties of DAZ were greatly improved ，and the dissolution rate was significantly increased. SC was statically quenched under the action of DAZ and the secondary structures of SC were changed. The crystallization process of DAZ was controlled under the action of SC ，and the interaction between DAZ and SC was mainly hydrogen bond and van der Waals force. CONCLUSIONS In this study ，DAZ-SC composite nanoparticles are successfully prepared. In the “bottom-up”technology，the interaction between SC and DAZ caused by hydrogen bond and van der Waals force inhibits the growth and agglomeration of drug crystals .

Objective:To study the effect ofmetformin combined with insulin aspart on the serum cholesterol(TC),total Bilirubin (TBil),uric Acid(UA),urinary Micro Protein(mAlb) levels and Maternal and Infant Outcomes of gravida with Gestational Diabetes Mellitus.Methods:84 patients ofgestational diabetes mellitus who received therapy from June 2014 to June 2016 in our hospital were selected.According to random number table,those patients were divided into the observation group (n=42) and the control group (n=42),on the basis of routine treatment,The control group was treated with insulin aspart,while the observation group was combined with metformin hydrochloride.The blood glucose index and the levels of TC,TBil,UA,mAlb and maternal and infant outcomes were compared.Results:After treatment,the levels of fasting blood glucose (FBG),postprandial 2h blood glucose (2hPG),glycosylated hemoglobin (HbA1c),TC,TBil,UA and mAlb in the observation group were significantly lower than the control group,the levels of TBil was significantly higher than the control group (P＜0.05);the incidence ofgestational hypertension,hydramnios,premature birth,cesarean section,giant child and neonatal jaundice were significantly lower than the control group (P ＜0.05).Conclusion:Metformin combined with insulin aspart was well for gestational diabetes mellitus,which could effectively improve the blood glucose indicators and TC,TBil,UA,mAlb levels,maternal and infant outcomes.

Objective Sperm screening is an essential step in IVF procedures. The swim-up method, an assay on sperm motility, is used clinically to select the ideal sperm for subsequent manipulation. However, additional parameters, including acrosome reaction capability, chemotaxis, and thermotaxis are also important indicators of mammalian sperm health. To monitor both sperm motility and chemotaxis simultaneously during sperm screening, we designed and constructed a microdevice comprising a straight channel connected with a bi-branch channel that mimics the mammalian female reproductive tract. Methods The width and length of the straight channel were optimized to select the motile sperm. Cumulus cells were selectively cultured in the bi-branch channel to generate a chemoattractant-forming chemical gradient. Sperm chemotaxis was represented by the ratio of the sperm swimming towards different branches. Results The percentage of motile sperm was improved from ( 58. 5 ± 3. 8 ) % to ( 82. 6±2.9)% by a straight channel 7 mm in length and 1 mm in width. About 10% of sperm were found chemotactically responsive in our experiment, which is consistent with previous studies. Conclusion The combined evaluation of both sperm motility and chemotaxis was achieved for the first time, and the motile and chemotactically responsive sperm can be easily enriched on a lab-on-a-chip device to improve IVF outcome.

Objective To study the expression of WWOX, ErbB2 and Ki67 protein in non-small cell lung cancer(NSCLC) and the relationships with cell proliferation. Methods WWOX and ErbB2 protein expressions were evaluated by immunohistochemistry in 81 NSCLC patients (50 squamous cell carcinomas,31 adenocarcinomas and 20 adjacent normal lung tissues) and the correlations with histopathologic cell proliferation were analyzed. Results WWOX expression was absent/reduced in 72.8% of NSCLC, while it was normal in 80.0% of adjacent normal lung tissues. WWOX expression was strongly associated with tumor histology, histologic grade and lymph node metastasis ( X2 = 5.44, P = 0.019 ; X2 = 4.740, P = 0.029, X2 = 4.51, P = 0.034 ), reduced WWOX expression was higher in squamous cell carcinomas and in poorly differentiated tumors. The overexpression of ErbB2 was associated with TNM stage and lymph node metastasis ( X2 = 6.90, P = 0.009 ; X2= 5.68, P=0.017). WWOX expression was negatively related to the overexpression of ErbB2 (r=-0.239, P <0.05 ). WWOX expression intensity was nega-tively related to the high index of cell proliferation (r=-0.252, P<0.05 ). Conclusion The loss of WWOX ex-pression plays different roles in tumorigenesis of NSCLC and is related to high aggressiveness of tumors. The loss of WWOX expression and the overexpression of ErbB2 can estimate the prognosis of NSCLC.

Objective To study the expression of WWOX gene in non-small cell lung cancer and its significance. Methods WWOX protein expression was evaluated by immunohistochemistry in 81 NSCLC patients(50 squamous cell carcinomas,31 adenocarcinomas and 20 adjacent normal lung tissues),and correlation with histopathologic(histotype,grade,tumor-node-metastasis,stage) and clinical characteristics was studied. Results WWOX expression was absent/reduced in 72.8% of NSCLC,whereas it was normal in 80.0% of adjacent normal lung tissues.WWOX expression was strongly associated with tumor histology and histologic grade(P

Object To study the preparation and technology on sinomenine (SM) release from Sinomenine Sustained-release Tablets (SSTs) in which hydroxypropyl methyl cellulose (HPMC) was used as the primary excipients. Methods SSTs were prepared with different HPMC viscosity of K4M, K15M, and K100M, different HPMC content, and preparing technology. Results Little effect was observed on the releasing rate of SM with different HPMC viscosity when the content of HPMC was 30%. SM releasing rate increased with the decreasing of proportion of HPMC while the content of HPMC was less than 30%. But the releasing velocity slowed down while the content of HPMC increased and the effect on the releasing rate was not found as the content of HPMC was over 30%. When the ratio of SM and HPMC was 1∶1.5, the releasing rate decreased with the increasing of tablet weight from 280 mg to 360 mg. The releasing rate was insensitive to the particle size of HPMC and hardness of SSTs in this study. Conclusion It is necessary to control the tablet weight and choose the proper quantity of HPMC in the preparation of SSTs.

Object To study the release mechanism of slow released tablet of puerarin (PUE) prepared by taking chistosan (CS) and sodium alginate (AL) as primary excipient. Methods The effect of the release in different conditions and the release mechanism was observed. Results No effect was found on release rate by basket and blade paddle methods, but the primary release (1 2 h) in different rotation speed showed the effect on drug release and the release rate was dependent on medium pH value (P