755-nm picosecond laser plus topical 20% azelaic acid compared to topical 20% azelaic acid alone for the treatment of melasma: a randomized, split-face and controlled trial.

PURPOSE: Melasma remains a refractory skin condition that needs to be actively explored. Azelaic acid has been used for decades as a topical agent to improve melasma through multiple mechanisms, however, there is a lack of research on its combination with laser therapy. This study evaluated the effectiveness of isolated treatment with topical 20% azelaic acid and its combination with 755-nm picosecond laser in facial melasma patients. METHODS: A randomized, evaluator-blinded, controlled study was conducted on 30 subjects with facial melasma in a single center from October 2021 to April 2022. All subjects received topical 20% azelaic acid cream (AA) for 24 weeks, and after 4 weeks, a hemiface was randomly assigned to receive 755-nm picosecond (PS) laser therapy once every 4 weeks for 3 treatments. Treatment efficacy was determined by mMASI score evaluations, dermoscopic assessment, reflectance confocal microscopy (RCM) assessments and patient's satisfaction assessments (PSA). RESULTS: Treatment with 20% azelaic acid, with or without picosecond laser therapy, significantly reduced the hemi-mMASI score (P < 0.0001) and resulted in higher patient satisfaction. Improvements in dermoscopic and RCM assessments were observed in both sides of the face over time, with no difference between the two sides. RCM exhibited better dentritic cell improvement in the combined treatment side. No patients had serious adverse effects at the end of treatment or during the follow-up period. CONCLUSION: The additional use of picosecond laser therapy showed no clinical difference except for subtle differences detected by RCM assessments.The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100051294; 18 September 2021).

Laser therapy in the treatment of melasma: a systematic review and meta-analysis.

Melasma is a highly prevalent and cosmetically disfiguring pigmented skin disease. The post-treatment results are often unsatisfactory. A large number of clinical trials have tried to prove the effectiveness of the combination therapy involving laser therapy, but the results have been indeterminate. This study aimed to evaluate the effectiveness of laser treatment for melasma via a systematic review and meta-analysis. We respectively searched 4 databases and clinicaltrials.gov as of June 8, 2021. Two researchers independently searched for literature and extracted data. Study outcomes were computed by weighted mean differences (WMD). All statistical analyses were performed by the Review Manager version 5.3, STATA version 14 software at 95% confidence interval. We obtained 22 eligible studies which involved a total of 694 patients. After the heterogeneity test and sensitivity analysis, we took a subgroup meta-analysis on the before and after treatment of different laser types. We found that most lasers and laser-based combinations were associated with reduced melasma area and severity index (MASI), such as low-fluence Q-switch 1,064-nm Nd: YAG laser (QSNYL) (WMD: - 2.76; 95% CI: - 3.53 to - 1.99), fractional ablative CO2 laser (WMD: - 9.36; 95% CI: - 12.51 to - 6.21), and fractional ablative 2940-nm Er: YAG laser (WMD: - 2,72; 95% CI: - 3.94 to - 1.49). Significant decrease was seen in neither MASI score of non-ablative 1550-nm fractional laser (WMD: - 1.29; 95% CI: - 2.80 to 0.21) and picosecond laser (WMD: - 0.58; 95% CI: - 1.43 to 0.27), nor melanin index (MI) of low-fluence QSNYL treatment (WMD: 10.17; 95% CI: - 4.11 to 24.46). When using laser to treat melasma, various adverse reactions may occur, most of which will resolve quickly without subsequent treatment, such as edema, erythema, scaling, and burning sensation after treatment. However, for patients with darker skin, there are risks of postinflammatory hyperpigmentation and hypopigmentation. The laser and laser-based combination treatment for melasma could significantly reduce the MASI score, which was showed by our systematic review and meta-analysis.

Selective photodynamic inactivation of Helicobacter pylori by a cationic benzylidene cyclopentanone photosensitizer - an in vitro and ex vivo study.

The rise in the antibiotic resistance rate of Helicobacter pylori has led to an increasing eradication failure of this carcinogenic bacterial pathogen worldwide. This underlines the need for alternative antibacterial strategies against H. pylori infection. Antimicrobial photodynamic therapy (aPDT) is a promising non-pharmacological antibacterial technology. In this study, the selective killing activities of three benzylidene cyclopentanone (BCP) photosensitizers (Y1, P1 and P3) towards H. pylori over normal human gastric epithelial GES-1 cells were evaluated and the ex vivo photodynamic inactivation effect was preliminarily assessed on twelve H. Pylor-infected mice. Results showed that under the irradiation of 24 J/cm2 532 nm laser, Y1, P1 and P3 at 2.5 µM induced a 3-log10 reduction of H. pylori CFU (99.9% killing). Confocal images showed that P3, unlike Y1 and P1, could not be uptaken by GES-1 cells. P3 at 2.5 to 20 µM showed not significant (p > 0.05) phototoxicity to GES-1 cells, nevertheless, Y1 and P1 under the same concentrations exhibited remarkable phototoxicity to GES-1 cells. In the co-culture of H. pylori and GES-1 cells, P3 at 2.5 µM led to a complete eradication of H. pylori under the irradiation of 24 J/cm2 532 nm laser. While for the GES-1 cells, no significant (p > 0.05) phototoxicity was observed under the same aPDT dosage. The ex vivo experiments showed that P3 mediated aPDT resulted in 82.4% to 100% reduction of H. pylori CFU without damaging the gastric mucosa. To sum up, P3 is a promising anti-H. pylori photosensitizer with the ability to selectively photo-inactivate H. pylori while sparing normal gastric tissues.

In vitro photodynamic inactivation effects of benzylidene cyclopentanone photosensitizers on clinical fluconazole-resistant Candida albicans.

BACKGROUND: The incidence of Candida infections has increased for various reasons, including, the more frequent use of immunosuppresants or broad-spectrum antibiotics. Photodynamic inactivation (PDI) is a promising approach for treating localized Candida infections. METHODS: The PDI efficacies of three benzylidene cyclopentanone-based (BCB) photosensitizers (PSs: P1, P2 and Y1) against three fluconazole-resistant C. albicans (cal-1, cal-2, and cal-3) and one control C. albicans (ATCC 90028), respectively, were evaluated using an established plate dilution method. The binding of PSs to C. albicans was determined by fluorescence spectroscopy. The mechanism of antifungal PDI was investigated using confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). RESULTS: Three BCB PSs all bound rapidly to C. albicans. After incubation with PSs for 30 min and irradiation with a 532 nm laser for 10 min (40 mW cm-2, 24 J cm-2), the fungicidal activity was achieved as 7.5 µM for P1 and P2, and 25 µM for Y1. CLSM confirmed that P1 and Y1 were located in intracellular components, including mitochondria, while P2 bound to the protoplast exterior and failed to enter the cells. TEM revealed the damage of mitochondria ultrastructures after P1- or Y1-mediated PDI, consistenting with the CLSM results. However, most cells became edematous, enlarged or deformation after P2-mediated PDI. CONCLUSIONS: The three BCB PSs all have remarkable PDI effects on C. albicans. The best effect is obtained by P1, which has one cationic charge with a proper lipophilicity. The respective subcellular localization of the three PSs led to different PDI mechanisms.

A series of water-soluble photosensitizers based on 3-cinnamoylcoumarin for in vitro antimicrobial photodynamic inactivation.

A series of novel water-soluble photosensitizers (PSs; M1-M5) based on 3-cinnamoylcoumarin derivatives, incorporating carboxylic acid salt (M1, M2), pyridine salt (M3, M4) and quaternary ammonium salt (M5) groups, were designed and synthesized. Their photophysical and photochemical properties and in vitro antimicrobial photodynamic inactivation (PDI) were investigated. M2, modified with two carboxylic acid salts, was unstable in phosphate-buffered saline (PBS). The four other PSs all showed higher binding/uptake to methicillin-resistant Staphylococcus aureus (MRSA), A. baumannii and C. albicans compared with the clinical drug methylene blue (MB), except for M1 to A. baumannii. Furthermore, the three cationic PSs (M3-M5) exhibited equivalent antibacterial PDI efficacies against MRSA and A. baumannii compared with MB. The antifungal efficacies of M4 and M5 to C. albicans were both significantly higher than that of MB, especially for M5, indicating that the quaternary ammonium-salt-modified coumarin derivative has substantial potential for antifungal PDI.

Clinical manifestations and cerebrospinal fluid status in ocular syphilis in HIV-Negative patients.

BACKGROUND: Syphilis with ocular involvement has reemerged as a critical health problem. The aim of the present study was to explore the clinical manifestations and cerebrospinal fluid (CSF) status in ocular syphilis in human immunodeficiency virus (HIV)-negative patients. METHODS: The clinical records of patients with ocular syphilis presenting to the Shanghai Xuhui Central Hospital in the period from January 2011 to December 2012 were retrospectively reviewed. RESULTS: The median age of 25 HIV-negative patients with ocular syphilis was 53 years, 18 patients (72.0 %) were males and 7 (28.0 %) were females. None of them self-identified themselves as men who had sex with men (MSM). The ocular lesions included: uveitis (13 cases), optic neuropathy (6 cases), retinal vasculitis (5 cases), retinal detachment (3 cases), and neuroretinitis (4 cases). Serum toluidine red unheated serum test (TRUST) titer ranged from 1 to 512, with a median of 64. Overall, 18 (72.0 %) of the 25 patients had abnormal CSF results, 15 (60.0 %) CSF samples had elevated white blood cell counts, 13 (52.0 %) had elevated protein levels, and 9 (36.0 %) had reactive CSF Venereal Disease Research Laboratory (VDRL) test, respectively. Mann-Whitney U tests showed higher serum TRUST titer (>32) correlated with the abnormal CSF results. CONCLUSIONS: The demographic characteristics of patients with ocular syphilis in this study were different from previous reports. The study showed a high CSF abnormal rate in HIV-negative patients. The recommendation for CSF examination from all patients with ocular syphilis, including HIV-negative cases, is strongly supported by the present data.

Assessment of Scientific Reasoning: the Effects of Task Context, Data, and Design on Student Reasoning in Control of Variables.

Scientific reasoning is an important component under the cognitive strand of the 21st century skills and is highly emphasized in the new science education standards. This study focuses on the assessment of student reasoning in control of variables (COV), which is a core sub-skill of scientific reasoning. The main research question is to investigate the extent to which the existence of experimental data in questions impacts student reasoning and performance. This study also explores the effects of task contexts on student reasoning as well as students' abilities to distinguish between testability and causal influences of variables in COV experiments. Data were collected with students from both USA and China. Students received randomly one of two test versions, one with experimental data and one without. The results show that students from both populations (1) perform better when experimental data are not provided, (2) perform better in physics contexts than in real-life contexts, and (3) students have a tendency to equate non-influential variables to non-testable variables. In addition, based on the analysis of both quantitative and qualitative data, a possible progression of developmental levels of student reasoning in control of variables is proposed, which can be used to inform future development of assessment and instruction.

[Alteration of retinoid X receptor alpha mRNA level after acitretin and/or narrow-band UVB treatment in normal human keratinocytes].

OBJECTIVE: To investigate the alteration of retinoid X receptor alpha (RXRalpha) mRNA level in normal human keratinocytes after acitretin and/or NB-UVB irradiation treatment. METHODS: After a 12-hour incubation with 10(-7)-10(-6) mol/L acitretin and/or following 50-100 mJ/cm2 NB-UVB irradiation in normal human keratinocytes, RXRalpha mRNA expression was examined by reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR. RESULTS: The expression of RXRalpha mRNA was obviously decreased by NB-UVB irradiation, but not by acitretion single treatment. When combining acitretin treatment with NB-UVB irradiation, greater decreased RXRalpha mRNA expression was observed than that of single treatment. CONCLUSION: Narrow-band UVB irradiation treatment can decrease RXRalpha mRNA expression, but not acitretin single treatment. Combining treatment with both can produce synergistic inhibition effects.

[Mutation detection of ATP2C1 gene in Chinese patients with Hailey-Hailey disease].

OBJECTIVE: To investigate the mutations of ATP2C1 gene in Chinese patients with Hailey-Hailey disease (HHD). METHODS: Genomic DNA was extracted from peripheral blood leukocytes. PCR and direct DNA sequencing were used to detect the mutations in all 27 exons of ATP2C1 gene in patients of two Chinese families and a sporadic patient with HHD. RESULTS: Three mutations in ATP2C1 gene were found, including 1 nonsense mutation, 1 deletion/frameshift mutation and 1 missense mutation. All of them were novel mutations. CONCLUSION: All the three mutations could affect the transcription and translation, and further the function of protein encoded by ATP2C1 gene.

[Synergistic effects of acitretin and narrow-band ultraviolet-B in inducing retinoic acid receptor gamma mRNA expression in normal human keratinocytes].

OBJECTIVE: To investigate the changes in cell proliferation and retinoic acid receptor gamma (RARgamma) mRNA expression in normal human keratinocytes after acitretin treatment and/or narrow-band ultraviolet-B irradiation. METHODS: Normal human keratinocytes were exposed to irradiation with 100 mJ/cm square NB-UVB and/or subsequent 12-hour incubation with 1x10(-6) mol/L acitretin, and the expression of RARgamma mRNA in the cells was examined using RT-PCR and real-time quantitative RT-PCR. RESULTS: A 0.9- and a 2.3-fold increase in RARgamma mRNA expression was induced in the cells by exposure to 100 mJ/cm square NB-UVB and 10(-6) mol/L acitretin, respectively, and the expression was synergistically enhanced by 2.8-fold after their combined treatment. CONCLUSION: Upregulated expression of RARgamma mRNA can be associated with keratinocyte growth inhibition after treatment with acitretin and NB-UVB irradiation.

A new mutation of the double-stranded RNA-specific adenosine deaminase gene in a family with dyschromatosis symmetrica hereditaria.

BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules localized on the back of the extremities and caused by mutations in the double-stranded RNA-specific adenosine deaminase (DSRAD) gene. OBJECTIVE: To identify gene mutations of DSRAD in patients with DSH. METHODS: A Chinese pedigree of typical DSH was subjected to mutation detection in DSRAD. Direct sequencing of all PCR products of the whole coding regions of DSRAD was performed to identify the mutation. RESULTS: A missense mutation 2747G-->T in the DSRAD gene was found in the affected members but not in the healthy individuals in this family and in 50 unrelated controls. CONCLUSION: Our study found a novel missense mutation in exon 9 of the DSRAD gene. We add new variants to the knowledge of DSRAD mutations in DSH.

[Investigation of steroid sulfatase gene in two pedigrees with X-linked ichthyosis].

OBJECTIVE: To investigate the gene mutation in two pedigrees with X-linked ichthyosis (XLI) and explore the relationship between the mutation and clinical manifestations. METHODS: Genomic DNA of the affected and normal members of the pedigrees and 50 unrelated normal subjects from different regions was extracted with a whole blood genomic DNA extraction kit for use of the template for PCR amplification of exon 1, exon 2 and exon 10 of the steroid sulfatase (STS) gene. RESULTS: The STS gene was partially deleted in the affected members in the pedigrees with XLI, leaving only exon 1 but not the other exons. The normal member of the pedigree and 50 unrelated normal subjects had no such deletion. CONCLUSION: Partial deletion of the STS gene exists in the two pedigrees with XLI, which is responsible for pathological skin changes characteristic of XLI.