Evaluation of 30% supramolecular salicylic acid followed by 1565-nm non-ablative fractional laser on facial acne and subsequent enlarged pores.

The treatment of acne vulgaris and enlarged pore remains challenging. The 30% supramolecular salicylic acid (SSA) is a newly developed form of SA which affects pathogenic factors of acne. Non-ablative fractional laser (NAFL) promotes remodeling and decreases sebum excretion with minimal side effect. The current study was aimed to evaluate the sequential modality with 30% SSA followed by 1565-nm NAFL on facial acne and subsequent enlarged pores. A 20-week-duration prospective study was performed. Consecutive 4 sessions of 30% SSA treatment were conducted, at 2-week intervals. Two weeks after the last session of 30% SSA, 3 sessions of 1565-nm NAFL treatment were applied, at 4-week intervals. The noninvasive devices measured scores of red areas and pores, cuticle moisture, and sebum secretion. The main subjective evaluation was global acne grading system (GAGS). The side effects were recorded. Compared to baseline, the scores of red areas and pores, sebum secretion, and GAGS significantly decreased after series sessions of 30% SSA treatments (P < 0.05). The sequential application of 1565-nm NAFL maintained the good results (P < 0.05, comparing to baseline) and even further decreased the sebum secretion (P < 0.05, comparing to SSA). The cuticle moisture remained unchanged during whole period, and side effects including tingling sensation, pain, erythema, and edema were quickly reversible and acceptable. The significant improvements of acne and pores were produced by 30% SSA, and 1565-nm NAFL inhibited the sebum secretion and maintained the efficacies of 30% SSA. The sequential modality of 30% SSA followed by 1565-nm NAFL was an alternative choice for acne vulgaris companied with enlarged pores.

A Comparison of Three Cylindrical Treatment Strategies for Topography-Guided LASIK: Manifest, Topographic, and ZZ VR Cylinders.

Purpose: This study was designed to compare the clinical outcomes of three cylindrical treatment strategies using manifest, topographic, and Zhang & Zheng vector-compensated refraction (ZZ VR) cylinders, for topography-guided laser-assisted in situ keratomileusis (LASIK) and to identify the laser programming strategy that optimizes refractive astigmatism outcomes and visual acuity. Methods: Consecutive patients referred for therapeutic refractive surgery between March and September 2018 at a single center were prospectively analyzed. Using double-masked simple randomization, patients were randomly assigned to undergo treatment based on manifest cylinder, topographic cylinder, and ZZ VR cylinder strategies. Uncorrected distance visual acuity and astigmatic refraction were analyzed preoperatively and 6 months postoperatively. Results: A total of 138 eyes from 71 patients met the inclusion criteria. The manifest group consisted of 46 eyes in 24 patients, the topographic group consisted of 43 eyes in 22 patients, and the ZZ VR group consisted of 49 eyes in 25 patients. The absolute residual cylindrical refractions at 6 months postoperatively in these three groups were 0.69 ± 0.32 D, 0.58 ± 0.31 D, and 0.42 ± 0.19 D, respectively (P < 0.001; adjusted P < 0.01 for manifest vs ZZ VR, adjusted P = 0.08 for topographic vs ZZ VR). The percentages of postoperative absolute residual cylindrical power within 0.50 D in the manifest, topographic, and ZZ VR groups were 30.4%, 55.8%, and 59.2%, respectively (P = 0.01; adjusted P = 0.06 for manifest vs topographic, adjusted P = 0.02 for manifest vs ZZ VR). Conclusion: The ZZ VR strategy may achieve better outcomes, as determined by cylindrical correction and visual activity, during topography-guided LASIK. Clinical Trial Registration Number: ChiCTR1900025779.

Safety, Tolerability, and Pharmacokinetics of Recombinant Human Neuregulin-1 in Healthy Chinese Subjects.

BACKGROUND: We investigated the safety, tolerability, and pharmacokinetics of intravenous recombinant human Neuregulin-1 (rhNRG-1), a DNA recombinant protein for the treatment of chronic heart failure, in healthy Chinese volunteers following single and multiple dose administration. METHODS AND RESULTS: To evaluate the safety and tolerance after single-dosing escalation, 28 subjects were divided into six groups (0.2, 0.4, 0.8, 1.2, 1.6, and 2.4 µg/kg) to receive an intravenous (IV) infusion of rhNRG-1 over 10 min by a randomized, open-label design. Only the 1.2 µg/kg dose group obtained pharmacokinetic parameters: Cmax was 7.645 (24.21) ng/mL, AUC0-t was 97.088 (21.41) min·ng/mL. To assess the safety and pharmacokinetics after multiple-dosing, 32 subjects were divided into four groups (0.2, 0.4, 0.8, and 1.2 µg/kg) to receive a 10-min IV infusion of rhNRG-1 for five consecutive days. After multiple dosing of 1.2 µg/kg, the Cmax value at day 5 was 8.838 (51.6) ng/mL and the AUC0-t value at day 5 was 109.890 (32.99) min·ng/mL. RhNRG-1 is rapidly cleared from the blood and has a short t1/2 of about 10 min. The adverse events related to rhNRG-1 mainly included flat or inverted T wave and gastrointestinal reactions, all of which were mild. CONCLUSIONS: It is concluded that rhNRG-1 is safe and well tolerated in healthy Chinese subjects at the dosing levels used in this study. The severity and frequency of adverse events did not increase with the prolongation of administration time. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) Identifier No. ChiCTR2000041107.

Identification of novel candidate genes and predicted miRNAs in atopic dermatitis patients by bioinformatic methods.

Atopic dermatitis (AD) is a common, chronic inflammatory dermatosis with relapsing eruptions. Our study used bioinformatics to find novel candidate differentially expressed genes (DEGs) and predicted miRNAs between AD patients and healthy controls. The Mesh term "atopic dermatitis" was retrieved to obtain DEGs in GEO datasets. DEGs between AD patients and healthy controls were analyzed using GEO2R. Overlapping DEGs between different datasets were obtained with use of Draw Venn software. GO and KEGG enrichment analyses were conducted by the use of DAVID. STRING and miRWalk were used to individually analyze PPI networks, interactions of candidate genes and predicted miRNAs. A total of 571 skin samples, as retrieved from 9 databases were assessed. There were 225 overlapping DEGs between lesioned skin samples of AD patients and that of healthy controls. Nineteen nodes and 160 edges were found in the largest PPI cluster, consisting of 17 up-regulated and 2 down-regulated nodes. Two KEGG pathways were identified, including the cell cycle (CCNB1, CHEK1, BUB1B, MCM5) and p53 (CCNB1, CHEK1, GTSE1) pathways. There were 56 nodes and 100 edges obtained in the miRNA-target gene network, with has-miR-17-5p targeted to 4 genes and has-miR-106b-5p targeted to 3 genes. While these findings will require further verification as achieved with experiments involving in vivo and in vitro modles, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Tolerance and pharmacokinetics of single-dose intravenous hemoporfin in healthy volunteers.

AIM: To investigate the safety, tolerability and pharmacokinetics of intravenous hemoporfin, a novel photosensitive drug for the treatment of port-wine stain (PWS), in healthy Chinese volunteers following single-dose administration. METHODS: Thirty-six healthy Chinese subjects were enrolled. The subjects were administered hemoporfin (2.5, 5, 7.5 or 10 mg/kg) via single-dose intravenous infusion. Pharmacokinetics of the drug were studied in the groups with doses of 2.5, 5 and 7.5 mg/kg, and tolerability was studied in all the 4 groups. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters, and pharmacokinetics were assessed by determining hemoporfin content with a validated high-performance liquid chromatography with fluorescence detection (HPLC/FLD) method. RESULTS: Mild and transient adverse events occurred in the trial (n=10), but none were serious, and no subjects were withdrawn from the trial. The gastrointestinal tract adverse events, such as nausea, stomach upset, abdominal pain and vomiting, were observed in the groups with doses of 7.5 and 10 mg/kg. Increased alanine aminotransferase (ALT) concentration was found in 3 subjects, and increased alkaline phosphatase (ALP) concentration in one subject. The half-life of hemoporfin for doses of 2.5, 5, and 7.5 mg/kg was 1.26 h, 1.31 h, and 1.70 h, respectively. C(max) and AUC increased with dose for intravenous single-dose administration of hemoporfin in the 2.5, 5, and 7.5 mg/kg groups. Urinary excretion of hemoporfin within 12 h was less than 0.2%. CONCLUSION: Hemoporfin is safe and well-tolerated in healthy Chinese volunteers at a single intravenous dose of up to 10 mg/kg. It was rapidly cleared from the blood and had a short half-life, which insures a short light-avoidance period.

Safety and pharmacokinetic studies of silodosin, a new α1A-adrenoceptor selective antagonist, in healthy Chinese male subjects.

The objectives of the study were to assess the safety and pharmacokinetics of silodosin capsules in 82 healthy male Chinese subjects. To evaluate the safety after single-dosing escalation, 40 subjects were equally divided into 4 groups (2, 4, 8, 12 mg) by a randomized, double-blind and placebo-controlled design. To assess the pharmacokinetics after single-dosing, 30 subjects were equally divided into 3 groups (4, 8, 12 mg). To assess the safety and pharmacokinetics via multiple-dosing, 12 subjects were included as a group (4 mg once daily at day 1 and day 7; 4 mg twice daily at day 2 through day 6). The safety observations showed that mild adverse events, including postural hypotension, dizziness, and headache, were observed. After single-dosing at doses of 4, 8, and 12 mg, the mean area under the concentration-time curve from 0 to 36 h (AUC(0-36)) values were 136.82±46.38, 270.17±54.66, and 474.63±108.50 µg/l·h and the mean maximal silodosin concentration in plasma (C(max)) values were 26.70±7.48, 48.47±12.35, and 94.07±22.59 µg/l, respectively. After multiple-dosing, the C(max) value at day 7 was 33.84±19.54 µg/l, and the AUC(0-24) value at day 7 was 193.19±68.96 µg/l·h. The accumulation ratio of the AUC value was 1.55 by comparing the multiple-dosing with the single-dosing. It is concluded that silodosin is safe and tolerated in healthy Chinese male subjects at the dosing levels used in this study. The mean C(max) and AUC values of silodosin increased proportionally with dose escalation, showing characteristics of linear pharmacokinetics.

Safety, pharmacokinetics and pharmacodynamics of single/multiple doses of the oral, direct Factor Xa inhibitor rivaroxaban in healthy Chinese subjects.

AIMS: To investigate the safety, pharmacokinetics and pharmacodynamics of rivaroxaban, an oral, direct Factor Xa (FXa) inhibitor, in healthy, male Chinese subjects. METHODS: Two randomized, single-blind, placebo-controlled, dose-escalation studies were conducted in healthy Chinese men aged 18-45 years. In the single-dose study, subjects received single, oral doses of rivaroxaban 2.5, 5, 10, 20 and 40 mg. In the multiple-dose study, oral rivaroxaban was administered in doses of 5, 10, 20 and 30 mg twice daily for 6 days. RESULTS: Rivaroxaban, in single and multiple doses up to 60 mg, was well tolerated. Rapid absorption was observed in both studies (time to C(max) 1.25-2.5 h). In the multiple-dose study, rivaroxaban exposure increased dose-proportionally after the first dose and at steady state (for the 5-20-mg doses). The half-life of rivaroxaban was up to 7.9 h in the single-dose study. Maximal inhibition of FXa activity was achieved within 1-3 h of dosing in the single-dose study [at 20 mg FXa inhibition as a median percentage change from baseline, 45.92; 95% confidence interval (CI) 44.64, 50.70] and 2-3 h after administration at steady state in the multiple-dose study (at 20 mg median FXa inhibition as a median percentage change from baseline, 60.25; 95% CI 56.16, 63.05), in line with maximum rivaroxaban plasma concentrations. CONCLUSIONS: Rivaroxaban demonstrated predictable pharmacokinetics and pharmacodynamics in healthy Chinese subjects, in line with findings observed previously in White subjects. This suggests that fixed doses of rivaroxaban may be administered to all patients, regardless of their ethnic origin.

Study of pharmacokinetics and cutaneous photosensitization of hemoporfin in healthy volunteers.

BACKGROUND: Hemoporfin is a porphyrin-based photosensitizer and has been used for photodynamic therapy of port wine stain birthmarks in China. This study assessed the pharmacokinetics and cutaneous photosensitization of Hemoporfin in healthy volunteers. METHODS: Sixteen healthy subjects received a single intravenous infusion injection of Hemoporfin (5 mg/kg). The concentrations of Hemoporfin (MHD) and its metabolite Haematoporphyrin (HP) in plasma, urine and faeces were determined. The pharmacokinetic parameters were calculated. In addition, the cutaneous photosensitization was evaluated under the irradiation of solar simulator, 532 nm laser, and sunlight. RESULTS: The Cmax of MHD and HP were 46.7 ± 8.41 and 1.04 ± 0.265 µg/ml, respectively. The t1/2 of MHD and HP were 5.09 ± 0.945 and 5.71 ± 2.65 h, respectively. The AUC0-24h of MHD and HP were 29.8 ± 6.19 and 0.757 ± 0.285 h·µg/ml, respectively. The AUC0-∞ of MHD and HP were 29.8 ± 6.2 and 0.792 ± 0.308 h·µg/ml, respectively. The cumulative fecal excretion rate of MHD and HP were 45.3% and 1.05% at 96 h, respectively. Whereas, the cumulative urinary excretion rate of MHD was only 0.132% at 96 h. The concentration of HP in urine was less than 10% of MHD. After 52 h of administration, the cutaneous photosensitization associated with the exposure to various light sources was minimal. CONCLUSION: MHD and HP were excreted mainly through the faeces after intravenous infusion. Hemoporfin associated cutaneous photosensitization was insignificant.

An intervention study to prevent gastric cancer by micro-selenium and large dose of allitridum.

BACKGROUND: People have more and more concerned about allitridum as studies have shown that taking more raw garlic associated with a lower risk for cancers of the alimentary system. In the present study, we tried to examine whether a large dose of allitridum and a microdose of selenium prevent gastric cancer. METHODS: A double-blind intervention study was performed on the participants aged (35 - 74) years, who had matched at least one of the following criteria: (1) a medical history of stomach disorder, (2) a family history of tumour, or (3) smoking and/or alcohol consumption. A total of 2,526 and 2,507 persons were randomly enrolled into intervention group and control group respectively from 288 natural villages of seven communities in Qixia County, Shandong Province, China. Each person of the intervention group orally took 200 mg synthetic allitridum every day and 100 microg selenium every other day for one month of each year during November 1989 to December 1991. At the same time, people in control group were given 2 placebo capsules containing corn oid with the identical appearance to that in the intervention group. RESULTS: For all subjects the large dose of allitridum was accepted and no harmful side effects were found during the study. In the first follow-up five years (1992 - 1997) after stopping the intervention, the morbidity rates of malignant tumours in the intervention group declined by 22%, in contrast to the control group, declined by 47.3%. After adjusting for age, gender, and other potential confounders, relative risks (RRs) for all tumours and gastric cancer of the whole population were 0.67 (95% CL: 0.43 - 1.03) and 0.48 (95% CL: 0.21 - 1.06), respectively, and for male group they were 0.51 (95% CL: 0.30 - 0.85) and 0.36 (95% CL: 0.14 - 0.92), respectively. No signigicantly protective effect was found for the female subgroup. CONCLUSION: The present study proves that large doses of allitridum and microdorse of selenium may effectively prevent gastric cancer, especially in men.