Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Preparation of the Levo-Tetrahydropalmatine Liposome Gel and Its Transdermal Study.

Purpose: The aim of this study was to develop a liposome gel containing levo-tetrahydropalmatine (l-THP) and evaluate its transdermal properties. Methods: A L16 (43) orthogonal experiment was conducted to optimize the preparation of l-THP liposomes and assess their characterization and stability in a gel. The transdermal features were analyzed through in vivo and in vitro experiments on rats and Strat-M® membrane, respectively. The metabolism of l-THP in liver and skin S9 fractions was also studied. Results: The optimization of the orthogonal experiment revealed that the ideal mass ratio of phosphatidylcholine, cholesterol, and l-THP during preparation was 10:1:3. The resulting liposome exhibited a particle size of 68 nm, a PDI of 0.27, a drug loading of 4.33%, an encapsulation of 18.79%, and a zeta potential of -41.27 mV. Both the l-THP and its liposome-gel formulation were found to be stable for a duration of 45 days at 4 °C and 30 °C. During the in vivo transdermal study, the maximum concentration (Cmax) of l-THP from the liposome gel was 0.16 µg/mL, and the time to reach this maximum concentration (tmax) was 1.2 hours. The relative bioavailability of l-THP in the liposome gel was 233.8% compared to the emulsion. The concentration of l-THP (prepared in PBS) decreased at a rate of 0.0067 µg/mL/min in the liver S9 fraction and 0.0027 µg/mL/min in the skin S9 fraction, however, this difference was not observed when l-THP was encapsulated in liposomes. l-THP passed through the Strat-M® membrane at a rate of 0.0032 mg/cm2/h and 0.002 mg/cm2/h for the emulsion and liposome gel, respectively. Conclusion: The optimal process for the preparation of l-THP liposomes was obtained. Compared to the emulsion, the liposomes provided greater bioavailability when used transdermally. The liposomes also provided greater stability for l-THP during storage.

Associations of urinary phenolic environmental estrogens exposure with blood glucose levels and gestational diabetes mellitus in Chinese pregnant women.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are considered to be related to diabetes, but studies of the association between phenolic EDCs and gestational diabetes mellitus (GDM) are limited. OBJECTIVES: To assess associations of maternal urinary bisphenol A (BPA), nonylphenol (NP), and 2-tert-octylphenol (2-t-OP) with GDM occurrence. METHODS: A cross-sectional study was performed among 390 Chinese women at 24-28 weeks of gestation. GDM was diagnosed with a 2-h 75-g oral glucose tolerance test (OGTT). BPA, NP, and 2-t-OP concentrations were determined in urine samples. Linear and logistic regression tests evaluated associations of BPA, NP, and 2-t-OP with blood glucose levels and GDM prevalence. RESULTS: The 2-t-OP concentrations in GDM patients were significantly higher than in non-GDM women with median values of 2.23 µg/g Cr and 1.79 µg/g Cr, respectively. No significant difference was observed in BPA and NP. Urinary 2-t-OP was positively associated with blood glucose levels after adjustment for several confounding factors and urinary BPA and NP. Higher 2-t-OP levels were associated with higher odds of GDM (OR: 5.78; 95% CI: 2.04, 16.37), whereas higher NP levels were associated with lower odds (OR: 0.22; 95% CI: 0.05, 0.85) in the adjusted models. In addition, compared to the first quartile of 2-t-OP, the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GDM in the second, third, and fourth quartiles were 2.81 (1.23, 6.42), 3.01 (1.30, 6.93), and 5.49 (2.24, 13.46), respectively. CONCLUSION: Our study indicates that, for the first time to our knowledge, exposure to 2-t-OP is associated with a higher risk of GDM. However, higher NP exposure is associated with lower GDM risk. Further studies are necessary to affirm the associations of 2-t-OP and NP with GDM, and to elucidate the causality of these findings.

A comparative study of three concentrations of intravenous nalbuphine combined with hydromorphone for post-cesarean delivery analgesia.

BACKGROUND: Nalbuphine has been suggested to be used for post-cesarean section (CS) intravenous analgesia. However, ideal concentration of nalbuphine for such analgesia remains unclear. The present study was conducted to explore an ideal concentration of nalbuphine for post-CS intravenous analgesia by evaluating the analgesic effects and side-effects of three different concentrations of nalbuphine combined with hydromorphone for post-CS intravenous analgesia in healthy parturients. METHODS: One-hundred-and-fourteen parturients undergoing elective CS were randomly allocated to one of three groups (38 subjects per group) according to an Excel-generated random number sheet to receive hydromorphone 0.05 mg/mL + nalbuphine 0.5 mg/mL (group LN), hydromorphone 0.05 mg/mL + nalbuphine 0.7 mg/mL (group MN), and hydromorphone 0.05 mg/mL + nalbuphine 0.9 mg/mL (group HN) using patient-controlled analgesia (PCA) pump. Visual analog scale (VAS) for pain, PCA bolus demands, cumulative PCA dose, satisfaction score, Ramsay score, and side-effects such as urinary retention were recorded. RESULTS: The number of PCA bolus demands and cumulative PCA dose during the first 48 h after CS were significantly higher in group LN (21 ±â€Š16 bolus, 129 ±â€Š25 mL) than those in group MN (15 ±â€Š10 bolus, 120 ±â€Š16 mL) (both P < 0.05) and group HN (13 ±â€Š9 bolus, 117 ±â€Š13 mL) (both P < 0.01), but no difference was found between group HN and group MN (both P > 0.05). VAS scores were significantly lower in group HN than those in group MN and group LN for uterine cramping pain at rest and after breast-feeding within 12 h after CS (all P < 0.01) and VAS scores were significantly higher in group LN than those in group MN and group HN when oxytocin was intravenously infused within 3 days after CS (all P < 0.05), whereas VAS scores were not statistically different among groups for incisional pain (all P > 0.05). Ramsay sedation scale score in group HN was significantly higher than that in group MN at 8 and 12 h after CS (all P < 0.01) and group LN at 4, 8, 12, 24 h after CS (all P < 0.05). CONCLUSIONS: Hydromorphone 0.05 mg/mL + nalbuphine 0.7 mg/mL for intravenous PCA could effectively improve the incisional pain and uterine cramping pain management and improve comfort in patients after CS. TRIAL REGISTRATION NUMBER: ChiCTR1800015014, http://www.chictr.org.cn/ Chinese Clinical Trial Registry.

Comparison of different regimens of pimecrolimus 1% cream in the treatment of facial seborrheic dermatitis.

BACKGROUND: Pimecrolimus 1% cream has already been proved to be an effective and safe alternative to treat seborrheic dermatitis. However, the treatment periods were inconstant in previous studies. OBJECTIVE: To evaluate the comparative efficacy of pimecrolimus 1% cream with different regimens for the treatment of facial seborrheic dermatitis. METHOD: Thirty patients with facial seborrheic dermatitis were enrolled and randomly distributed to three groups. Patients of Group 1 were treated with topical pimecrolimus cream 1% twice daily for 2 weeks and then a moisturizer cream twice daily for 2 weeks. Patients of Group 2 were treated with pimecrolimus cream 1% twice daily for 2 weeks and then once daily for another 2 weeks. Patients of Group 3 had a consecutive course of pimecrolimus cream 1% twice daily for 4 weeks. Objective symptoms, subjective symptoms, and dermatology life quality index (DLQI) were measured at weeks 0, 2, 4, and 6. RESULTS: At week 4, the clinical severity scores of all three regimens significantly decreased (P<.01). The improvement of total severity score in Group 3 was more remarkable than groups 1 and 2 (both P<.05). This effect was maintained until the end of the study in Group 3. Life quality of all three groups was significantly improved at week 4 (P<.001), while there was no statistical difference on the improvement of life quality among three groups. CONCLUSION: We recommend pimecrolimus 1% cream could be applied twice a day for 4 weeks to treat seborrheic dermatitis.

Identification of Differentially Expressed Genes in Kawasaki Disease Patients as Potential Biomarkers for IVIG Sensitivity by Bioinformatics Analysis.

Kawasaki disease (KD) is a leading cause of acquired heart disease predominantly affecting infants and young children. Intravenous immunoglobulin (IVIG) is applied as the most favorable treatment against KD, but IVIG resistant remains exist. Although several clinical scoring systems have been developed to identify children at highest risk of IVIG resistance, there is a need to identify sufficiently sensitive biomarkers for IVIG treatment. Some differentially expressed genes (DEGs) could be the promising potential biomarkers for IVIG-related sensitivity diagnosis. We employed a systematic and integrative bioinformatics framework to identify such kind of genes. The performance of the candidate genes was evaluated by hierarchical clustering, ROC analysis and literature mining. By analyzing three datasets of KD patients, 34 DEGs of the three groups have been found to be associated with IVIG-related sensitivity. A module of 12 genes could predict resistant group patients with high accuracy, and a module of ten genes could predict responsive group patients effectively with accuracy of 96 %. And three of them are most likely to serve as drug targets or diagnostic biomarkers in the future. Compared with unsupervised hierarchical clustering analysis, our modules could distinct IVIG-resistant patients efficiently. Two groups of DEGs could predict IVIG-related sensitivity with high accuracy, which are potential biomarkers for the clinical diagnosis and prediction of IVIG treatment response in KD patients, improving the prognosis of patients.

Identification of melanoma biomarkers based on network modules by integrating the human signaling network with microarrays.

BACKGROUND: Melanoma is a leading cause of cancer death. Thus, accurate prognostic biomarkers that will assist rational treatment planning need to be identified. METHODS: Microarray analysis of melanoma and normal tissue samples was performed to identify differentially expressed modules (DEMs) from the signaling network and ultimately detect molecular markers to support histological examination. Network motifs were extracted from the human signaling network. Then, significant expression-correlation differential modules were identified by comparing the network module expression-correlation differential scores under normal and disease conditions using the gene expression datasets. Finally, we obtained DEMs by the Wilcoxon rank test and considered the average gene expression level in these modules as the classification features for diagnosing melanoma. RESULTS: In total, 99 functional DEMs were identified from the signaling network and gene expression profiles. The area under the curve scores for cancer module genes, melanoma module genes, and whole network modules are 92.4%, 90.44%, and 88.45%, respectively. The classification efficiency rates for nonmodule features are 71.04% and 79.38%, which correspond to the features of cancer genes and melanoma cancer genes, respectively. Finally, we acquired six significant molecular biomarkers, namely, module 10 (CALM3, Ca 2+ , PKC, PDGFRA, phospholipase-g, PIB5PA, and phosphatidylinositol-3-kinase), module 14 (SRC, Src homology 2 domain-containing [SHC], SAM68, GIT1, transcription factor-4, CBLB, GRB2, VAV2, LCK, YES, PTCH2, downstream of tyrosine kinase [DOK], and KIT), module 16 (ELK3, p85beta, SHC, ZFYVE9, TGFBR1, TGFBR2, CITED1, SH3KBP1, HCK, DOK, and KIT), module 45 (RB, CCND3, CCNA2, CDK4, and CDK6), module 75 (PCNA, CDK4, and CCND1), and module 114 (PSD93, NMDAR, and FYN). CONCLUSION: We explored the gene expression profile and signaling network in a global view and identified DEMs that can be used as diagnostic or prognostic markers for melanoma.

Pimecrolimus cream 1% in the management of atopic dermatitis in pediatric patients: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of pimecrolimus cream 1% in the treatment of AD in the pediatric population. METHODS: PubMed, EMBASE, Web of Science and Cochrane library databases were searched till July 2013. The randomized and nonrandomized blinded studies of pimecrolimus cream 1% applied twice daily with Jaded score ≥ 3 in pediatric patients with AD were included. The efficacy outcomes included investigator global assessment (IGA), eczema area and severity index (EASI) scores, pruritus and care giver's assessments and flares free period. Adverse events were reviewed to assess the safety. RESULTS: Out of 81 studies, 7 were selected that enrolled 2,170 pediatric patients. The pooled analysis reported that pimecrolimus was no better to vehicle reducing eczema at day-8, day-26 and six weeks (OR 4.95, 95% CI 2.79-8.80), (OR 9.69, 95% CI 4.12-22.83) and (OR 3.83. 95% CI 1.94-7.56), respectively in children. Similarly, pimecrolimus did not show beneficial effects when analyzed for mild or absent pruritus at day 4 (OR 8.29, 95% CI 3.88-17.72 favoring vehicle), day 43 (OR 1.81 95% CI 1.13-2.89 favoring vehicle) and 1 week (OR 2.29, 95%CI 1.45 to 3.60 favoring vehicle) as compared with vehicle. One study comparing pimecrolimus with tacrolimus found no significant difference in achieving mild or absent pruritus (OR 0.94, 95% CI 0.44-1.99). More patients showed an improvement in overall disease in vehicle group at day 8 (OR 3.30, 95% CI 2.03-5.35), day 29 (OR 14.14, 95% CI 6.87-29.13) and day 43 (OR 4.11, 95% CI 2.59-6.52) as compared with pimecrolimus 1% group, as assessed by caregivers. No significant difference was seen between the total AEs in both groups (pimecrolimus vs vehicle/tacrolimus) (OR 1.19, 95% CI 0.85, 1.65). CONCLUSION: The results of the present meta-analysis showed that pimecrolimus cream 1% was not significantly better to vehicle for AD in pediatrics population.

A quantitative assessment of the effects of formal sun protection education on photosensitive patients.

PURPOSE: To quantitatively assess the effect of formal sun protection education on sun exposure habits and quality of life in photosensitive patients. METHODS: Patients with chronic actinic dermatitis (CAD) or polymorphous light eruption (PLE) were randomized to either the intervention or the control group. General advice about sun protection and broad-spectrum sunscreen were provided to all participants. The intervention group was given two additional intensive sun protection instruction classes at the beginning of spring and then in summer. At baseline and 12 months, each participant completed interviews that included a questionnaire about sun protection behaviors and a modified Dermatology Life Quality Index (DLQI) questionnaire. RESULTS: In the intervention group, after the first intensive sun protection instruction, all aspects of sun exposure habits were significantly improved from baseline (P < 0.01). At study's end, there had been no significant change in sun exposure habits in the control group compared with baseline, whereas sun exposure habits in the intervention group significantly improved (P < 0.01). After two intensive sun protection training sessions, the modified DLQI significantly decreased in the intervention group compared with baseline (P < 0.001), while no change was observed in the control group. CONCLUSION: Formal sun protection education improved sun exposure and protection behaviors as well as quality of life in photosensitive patients.