In Vivo Investigation of the Biostimulatory and Rejuvenating Effects of Small-Particle Cross-linked Hyaluronic Acid Injections in Photoaged Human Skin.

BACKGROUND: Injection of cross-linked hyaluronic acid (CLHA) has been traditionally utilized to treat wrinkles and provide volume. Recent studies have also shown that intradermal placement of CLHA provides lasting secondary effects and may be a useful method for improving skin appearance and physiology. OBJECTIVES: The aim of this study was to investigate the biostimulatory effects and potential underlying mechanisms induced by repeated intradermal microinjections of small-particle cross-linked hyaluronic acid (SPCLHA) for skin rejuvenation. METHODS: Eight patients with photoaged forearm skin underwent three intradermal microinjections of SPCLHA and isotonic sodium chloride (control). At 0, 4, 8, 12, and 24 weeks, biophysical parameters were measured, and skin biopsies were obtained at 12 and 24 weeks for assessment employing histological and immunohistochemical analyses, transmission electron microscope, and real-time fluorescence quantitative polymerase chain reaction. RESULTS: SPCLHA treatments significantly improved skin appearance and physiologic functions starting at 8 weeks. Histologic examination revealed thickening of the epidermis, more red-stained collagen fibers in the dermis, and increased formation of blood vessels in SPCLHA-treated skin. Immunohistochemical evaluation showed increased collagen deposition, proliferation of keratinocytes and fibroblasts, and cutaneous vascularity in SPCLHA-treated skin compared with controls. Fibroblasts appeared morphologically stretched with well-developed rough endoplasmic reticulum. Gene expression concerning various extracellular matrix (ECM) proteins and growth factors was upregulated at 12 weeks and several genes remained upregulated at 24 weeks. CONCLUSIONS: Intradermal microinjections of SPCLHA can stimulate production of collagen and other ECM components, restore the structural integrity of dermal microenvironment, and may be considered an effective method for skin rejuvenation.

Chin Microgenia: An Anthropometric Analysis on the Prevalence and Severity in a Chinese Population.

BACKGROUND: The chin is an important component of facial harmony, and deficient chins are associated with unattractiveness. Previous studies have reported microgenia as the most common subtype of chin deformities. OBJECTIVE: To investigate the prevalence and severity of microgenia in a Chinese population through facial anthropometric analysis. METHODS: A total of 800 Han Chinese adults from various age groups of both sexes were recruited for facial anthropometric measurements and photographic analysis. Chin deficiencies in both sagittal and vertical dimensions were evaluated using G-S-P angle, chin retrusion distance, and Sn-Vl/Sn-Me ratio criteria. RESULTS: In the sagittal dimension, microgenia was present in 60.7% of men and 68.6% of women according to the G-S-P angle criterion, and the angle significantly decreased with age in women (p < .05). According to the chin retrusion criterion, microgenia was present in 38.7% of men and 32.3% of women, and the retrusion distance significantly increased with age in both sexes (p < .05). Vertical microgenia was present in 69.6% of men and 81.9% of women according to the Sn-Vl/Sn-Me criterion, and the ratio gradually increased with age in both sexes (p < .05). CONCLUSION: Microgenia is common among Chinese, particularly in women, and the prevalence and severity increase with age.

Consensus of Chinese experts on protection of skin and mucous membrane barrier for health-care workers fighting against coronavirus disease 2019.

Health professions preventing and controlling Coronavirus Disease 2019 are prone to skin and mucous membrane injury, which may cause acute and chronic dermatitis, secondary infection and aggravation of underlying skin diseases. This is a consensus of Chinese experts on protective measures and advice on hand-cleaning- and medical-glove-related hand protection, mask- and goggles-related face protection, UV-related protection, eye protection, nasal and oral mucosa protection, outer ear, and hair protection. It is necessary to strictly follow standards of wearing protective equipment and specification of sterilizing and cleaning. Insufficient and excessive protection will have adverse effects on the skin and mucous membrane barrier. At the same time, using moisturizing products is highly recommended to achieve better protection.

Cornification of nail keratinocytes requires autophagy for bulk degradation of intracellular proteins while sparing components of the cytoskeleton.

Epidermal keratinocytes undergo cornification to form the cellular building blocks of hard skin appendages such as nails and the protective layer on the surface of the skin. Cornification requires the cross-linking of structural proteins and the removal of other cellular components to form mechanically rigid and inert corneocytes. Autophagy has been proposed to contribute to this intracellular remodelling process, but its molecular targets in keratinocytes, if any, have remained elusive. Here, we deleted the essential autophagy factor Atg7 in K14-positive epithelia of mice and determined by proteomics the impact of this deletion on the abundance of individual proteins in cornified nails. The genetic suppression of autophagy in keratinocytes resulted in a significant increase in the number of proteins that survived cornification and in alterations of their abundance in the nail proteome. A broad range of enzymes and other non-structural proteins were elevated whereas the amounts of cytoskeletal proteins of the keratin and keratin-associated protein families, cytolinker proteins and desmosomal proteins were either unaltered or decreased in nails of mice lacking epithelial autophagy. Among the various types of non-cytoskeletal proteins, the subunits of the proteasome and of the TRiC/CCT chaperonin were most strongly elevated in mutant nails, indicating a particularly important role of autophagy in removing these large protein complexes during normal cornification. Taken together, the results of this study suggest that autophagy is active during nail keratinocyte cornification and its substrate specificity depends on the accessibility of proteins outside of the cytoskeleton and their presence in large complexes.

Rapid remission of Stevens-Johnson syndrome by combination therapy using etanercept and intravenous immunoglobulin and a review of the literature.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are spectrum of rare, acute, and life-threatening delayed-type drug hypersensitivity reactions that are associated with high mortality rates. However, no therapeutic standard has been proposed for SJS/TEN. Here, we report a case of a patient diagnosed with Stevens-Johnson syndrome whose disease progression was halted by a single dose of etanercept and was treated successfully. In addition, we reviewed the literature reporting patients with SJS/TEN treated with similar regimens.

A Retrospective Study of Chinese-Specific Glabellar Contraction Patterns.

BACKGROUND: Botulinum toxin has been widely accepted as safe and effective for the treatment of glabellar lines, and previous studies have classified glabellar contraction patterns into 5 categories. OBJECTIVE: To classify the glabellar contraction patterns among a large-scale Chinese population and provide a reference for injections in Chinese patients. METHODS: Four hundred eighty-nine Chinese subjects who received botulinum toxin for the treatment of glabellar lines were selected for a retrospective photographic analysis of their glabellar contraction patterns. Using 2 separate previously established classification systems, the patterns were analyzed and classified by a panel of certified Chinese dermatologists. RESULTS: Two separate classification systems showed different distributions of glabellar contraction patterns among Chinese compared with Caucasians and Koreans. The classifications allowed for identification of the most frequent patterns in Chinese, which were "converging arrows" and "11" pattern, and provided references for identifying the most important muscles. CONCLUSION: Both classification systems are applicable to the Chinese population with varying distributions. Because the classification system of de Almeida and colleagues focuses more on the muscles involved in the formation of glabellar lines, the authors' subjects classified according to this system displayed a more balanced distribution among the 5 patterns. This provides an easier reference for dermatologists in daily clinical practice and guiding treatment strategies.

Botulinum toxin type A for the treatment of glabellar lines in Chinese: a double-blind, randomized, placebo-controlled study.

BACKGROUND: This is the first well-controlled study of the use of botulinum toxin type A (BoNTA) for glabellar lines in China. OBJECTIVES: To evaluate the safety and efficacy of BoNTA in the treatment of glabellar lines in Chinese subjects. MATERIALS AND METHODS: A total of 227 subjects received a single treatment in a 3:1 randomization ratio of BoNTA (20 U):placebo and were observed for 120 days after injection. Effective outcome measures included investigator's rating of wrinkle severity at maximum frown and rest and subjects' global assessment and self-perception of age. RESULTS: A significantly higher responder rate at maximum frown, ranging from 94.1% at day 30 to 52.9% at day 120, was noted in the BoNTA group. The proportion of subjects with none or mild glabellar lines at rest was 66.7% in the BoNTA group at day 30. Most (95.3%) of the subjects treated with BoNTA reported better than 50% improvement at day 30, and self-perception of age was less than chronological age. There were no statistically significant differences in adverse events reported between the two groups (p=.06). CONCLUSION: A single treatment of 20 U of BoNTA was effective and safe in reducing glabellar lines in Chinese subjects.

A randomized study showing improved skin quality and aesthetic appearance of dorsal hands after hyaluronic acid gel treatment in a Chinese population.

BACKGROUND: Patients are increasingly aware of the aesthetic appearance of aging hands. AIMS: To evaluate efficacy and safety of a hyaluronic acid gel for improving skin quality in aged skin of the dorsal hand. METHODS: This was a 15-month randomized, multi-center, evaluator-blinded, split-hand, no treatment-controlled study. Three treatments with hyaluronic acid gel were administered in the same hand in adult Chinese subjects with grade 2 or 3 (mild or moderate aging) on the Hand Grading Scale (HGS). The primary objective was to evaluate the difference at 3 months between treated and untreated hands, based on the blinded evaluator's HGS assessment. Secondary assessments included the Global Aesthetic Improvement Scale (GAIS), biophysical measurements (skin elasticity, skin roughness and hydration), and subject satisfaction. Safety was evaluated by incidence of adverse events. RESULTS: A total of 100 subjects were enrolled. Clinically relevant differences in HGS favored HA gel (P < .0001). At 15 months, 87%-96% of treated hands were still improved according to GAIS (per evaluator and subject, respectively). Objective measures of skin quality improved, confirmed by evaluators and highly satisfied subjects. Treatment was well tolerated. CONCLUSIONS: Hyaluronic acid treatment improved skin quality and reduced the aging appearance of the hand, with high subject satisfaction.

Two new compounds from the dried tender stems of Cinnamomum cassia.

Two new compounds, cinnamic aldehyde cyclic d-galactitol 3'R,4'S-acetal (1) and cinnamomumolide (2), along with six known compounds, syringaresinol (3), lyoniresinol (4), 5,7,3'-trimethoxyl-( - )-epicatechin (5), 5,7-dimethoxyl-3',4'-di-O-methylene-( +/- )-epicatechin (6), 2-methoxyl-4-hydroxy cinnamyl aldehyde (7), and glucosyringic acid (8), have been isolated from the dried tender stems of Cinnamomum cassia. Their structures were elucidated based on spectroscopic data. Compound 2 was elucidated as 8-methoxyl-9-hydroxy-3',4'-methylenedioxy-3S,4R-diphenyl butyrolactone, named cinnamomumolide, which exhibited activity in protecting against the injury caused by hydrogen peroxide oxidation on human umbilical vein endothelial cells, with an EC(50) value of 10.7 microM. Compounds 3-8 were isolated from the title plant for the first time.

Generalized Cutaneous Nodules on the Trunk and Extremities.

A 61-year-old man presented with rapidly growing and itchy cutaneous nodules all over his body and prominent lymphadenopathies. What is your diagnosis?

Clinical comparison between two hyaluronic acid-derived fillers in the treatment of nasolabial folds in Chinese subjects: BioHyalux versus Restylane.

Hyaluronic acid fillers are used to improve the appearance of nasolabial folds (NLF). This study aimed to compare the efficacy, safety, and durability of a new hyaluronic acid gel (BioHyalux) versus Restylane for the correction of NLF. This was a multicenter, double-blinded, randomized, controlled, non-inferiority clinical trial involving 88 subjects with moderate to severe NLF. Subjects were randomized to BioHyalux and Restylane on either sides of the NLF. NLF was assessed before and right after injection, and at 1 week, 1, 3, and 6 months. Patients were followed up for 13-15 months to evaluate the durability and long-term safety. A clinically meaningful response was predefined as at least one-point improvement on the Wrinkle Severity Rating Scale, which is a five-point scale. At 6 months, the response rate of BioHyalux was not inferior to that of Restylane (P < 0.05). At the 13-15 months follow-up, the response rate by investigators was 58.0 % on the BioHyalux side versus 63.8 % on the Restylane side. The response rate by subjects showed similar results, which was 56.5 % on the BioHyalux side versus 60.9 % on the Restylane side at 13-15 months. The subjects' Global Aesthetic Improvement Scale (GAIS) showed that most subjects felt improvements on both sides of NLF (P > 0.05) at all time points. At 6 months, 100 % reported improvements on both side; at 13-15 months, 60 % of subjects reported improvements with BioHyalux versus 64 % with Restylane. Adverse events were transient and predominantly mild or moderate in severity including injection site swelling, pain, itching, bruising, and tenderness. BioHyalux had reliable safety and tolerance, and could be an effective injectable filler for correcting NLF.

Reduction of facial pigmentation of melasma by topical lignin peroxidase: A novel fast-acting skin-lightening agent.

The aim of the present study was to evaluate the efficacy and safety of lignin peroxidase (LIP) as a skin-lightening agent in patients with melasma. A self-controlled clinical study was performed in 31 women who had melasma on both sides of the face. This study involved 8 weeks of a full-face product treatment. The skin color was measured at days 0, 7, 28 and 56 using a chromameter on the forehead and cheeks. Standardized digital photographic images of each side of the face of all subjects were captured by a complexion analysis system. Clinical scores of the pigmentation were determined by two dermatologists. After using the LIP whitening lotion for 7 days, the luminance (L*) values of the melasma and the normal skin were significantly increased from baseline. The L* values continued to increase at days 28 and 56. The melasma area severity index (MASI) score was statistically decreased after 28 days of treatment. No treatment-related adverse events were observed. LIP whitening lotion was able to eliminate the skin pigmentation after 7 days of treatment, and provides a completely innovative approach to rapid skin lightening. The LIP whitening lotion exhibited good compatibility and was well tolerated.

Fetal human keratinocytes produce large amounts of antimicrobial peptides: involvement of histone-methylation processes.

Antimicrobial peptides (AMPs), an important part of the innate immune system, are crucial for defense against invading microorganisms. Whereas AMPs have been extensively studied in adult skin, little is known about the impact of AMPs in the developing human skin. We therefore compared the expression and regulation of AMPs in fetal, neonatal, and adult keratinocytes (KCs) in vitro. The constitutive expression of human ß-defensin-2 (HBD-2), HBD-3, S100 protein family members, and cathelicidin was significantly higher in KCs from fetal skin than in KCs from postnatal skin. The capacity to further increase AMP production was comparable between prenatal and postnatal KCs. Analysis of skin equivalents (SEs) revealed a strong constitutive expression of S100 proteins in fetal but not in neonatal and adult SEs. The elevated AMP levels correlated with reduced H3K27me3 (tri-methyl-lysine 27 on histone H3) levels and increased expression of the histone demethylase JMJD3. Knockdown of JMJD3 in fetal KCs elevated H3K27me3 levels and significantly downregulated the expression of HBD-3, S100A7, S100A8, S100A9, and cathelicidin. Our data indicate a crucial contribution of histone modifications in the regulation of AMP expression in the skin during ontogeny. The elevated AMP expression in prenatal skin might represent an essential defense strategy of the unborn.

Depigmentation of melanocytes by the treatment of extracts from traditional Chinese herbs: a cell culture assay.

OBJECTIVE: To obtain potential skin whitening agents from traditional Chinese herbs, we tested changes of melanin content in melanocyte cell lines after treatment with extracts of 90 traditional Chinese herbs. METHODS: Mouse melanocyte cell lines were used. Depigmentation activity of the herb extracts were first screened in Mel-Ab cells, and then re-evaluated in melan-a cells and co-culture of melan-a and SP-1 cells. Melanin content and cell viability were the two indications for evaluation. Tyrosinase activity and the expression of melanin synthesis related enzymes in cells treated with the herb extracts were also tested. RESULTS: Nine herb extracts were proved to have depigmentation activity similar to or better than that of arbutin and low cytotoxicity to melanocytes. Two of them were more effective in co-cultured melan-a cells. Most of the effective herb extracts inhibited tyrosinase activity and the expression of tyrosinase. Some of them also inhibited tyrosinase related protein-1 and/or tyrosinase related protein-2 in cultured cells. CONCLUSIONS: We have found 9 herb extracts to be promising skin whitening agents. Among them, water extract of Galla Chinensis and ethanol extract of Radix Clematidis exhibited higher depigmentation activity and caused lower tyrosinase activity in cell culture assays and are worthy to be further studied.