Effect of black cloth ointment on hypertrophic scar formation: An investigation using integrated network pharmacology and animal assay.

BACKGROUND: Hypertrophic scars (HS) are a common disfiguring condition in daily clinical encounters which brings a lot of anxieties and concerns to patients, but the treatment options of HS are limited. Black cloth ointment (BCO), as a cosmetic ointment applicable to facial scars, has shown promising therapeutic effects for facial scarring. However, the molecular mechanisms underlying its therapeutic effects remain unclear. MATERIAL AND METHODS: Network pharmacology was first applied to analyze the major active components of BCO and the related signaling pathways. Subsequently, rabbit ear scar model was successfully established to determine the pharmacological effects of BCO and its active component ß-elemene on HS. Finally, the molecular mechanism of BCO and ß-elemene was analyzed by Western blot. RESULTS: Through the network pharmacology, it showed that ß-elemene was the main active ingredient of BCO, and it could significantly improve the pathological structure of HS and reduce collagen deposition. BCO and ß-elemene could increase the expression of ER stress-related markers and promote the increase of apoptotic proteins in the Western blot experiment and induce the apoptosis of myofibroblasts. CONCLUSIONS: Our findings indicate that the material basis for the scar-improving effects of the BCO is ß-elemene, and cellular apoptosis is the key mechanism through which the BCO and ß-elemene exert their effects.

The differential diagnosis of lichenoid keratosis and seborrheic keratosis with reflectance confocal microscopy: a preliminary study.

BACKGROUNDS AND OBJECTIVES: Lichenoid keratosis (LK, or lichen planus-like keratosis, LPLK) and seborrheic keratosis (SK) present as similar benign keratotic lesions on cosmetically sensitive area, but require different therapies. Both lesions can be easily differentiated based on histological evaluation of biopsy materials. However, the biopsies may cause scarring and result in hyper-pigmentation, which reduces the compliance of the patients to be treated. In this study, we investigated the role of reflectance confocal microscopy (RCM) in the non-invasive differential diagnosis of LK and SK. PATIENTS AND METHODS: Cases with facial brown patches or plaques suspicious of SK were enrolled in the study. After written informed consent was obtained, the lesions were photographed, imaged by RCM, and then biopsied. The RCM findings were analyzed and correlated with histology results. Evaluation of the RCM pictures and confirmation with histological results were conducted by two independent dermatologists. RESULTS: In total, 10 cases were enrolled in the study. The main characteristics of LK lesions observed by RCM were the disarray of the dermal-epidermal junction (DEJ), and marked inflammatory infiltrates in the superficial dermis; while prominent cerebriform pattern, or elongated cords with bulbous projections without significant inflammation reaction, were the features of SK. Among the 10 cases, clinically suspicious of facial SK, 4 were determined as LK, 6 as SK by RCM imaging, and all the RCM findings were confirmed by histological results. CONCLUSIONS: The RCM features of LK and SK have significant difference, highlighting the important role of RCM in the differential diagnosis of LK and SK, avoiding biopsies and allowing safe treatments.

Topical metformin suppresses angiogenesis pathways induced by pulsed dye laser irradiation in animal models.

Pulsed dye laser (PDL) is the first-line treatment for port-wine stain (PWS). However, only a small portion of the lesions could be completely cleared by PDL treatment, which might be related to the regeneration and revascularization of the vascular structures after laser irradiation. Recently, it is believed that the suppression of regeneration and revascularization of photocoagulated blood vessels can achieve a better therapeutic outcome. We use rabbit ear and SD rat as the animal models to investigate whether PDL-induced angiogenesis can be suppressed by topical metformin. Our results showed that topical application of metformin can effectively suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in animal models.

Treatment of striae albae with 1,550 nm Er: Glass vs. CO2 fractional laser: A self-controlled study.

Objective: The objective of this study was to compare the efficacy and safety of fractional CO2 laser and 1,550 nm Er: glass laser in the treatment for the patients with striae albae. Methods: The female adults with striae albae in the abdomen for at least 12 months were recruited. After informed consent obtained, the patient received three treatments at 2-month intervals. The lesions on the left abdomen were treated with 10,600 nm CO2 fractional laser and right side treated with 1,550 nm Er: glass fractional laser. The pictures were taken before each visit and 3 months after the final treatment. The criteria for the evaluations using a quartile grading scale were excellent (76-100%), good (51-75%), fair (26-50%), poor (1-25%), and no improvement (0%). The safety and efficacy of the two lasers were independently evaluated using before and after photographs by two dermatologists. In addition, the self-reports to investigate the pain and satisfaction from patients were also recorded. Results: Totally, 27 cases were recruited, and 25 patients completed the treatments and follow-up. The excellent and good results (improvement of 51-100%) were achieved on the right abdomen in 84% of the patients, while 48% on the left site (p < 0.05). Hyper-pigmentation was seen in 20% of the patients assessed on the left abdomen and only in 8% on the right abdomen. During the treatments, average score of the pain on the right abdomen was 5.41 ± 2.13, which was higher than that on the left (4.19 ± 2.12) (p < 0.001). No permanent hyper-pigmentation was found on the both sides. Considering the whole treatments, the patients favored the modality used on the right side (80 vs. 68%, p < 0.05). Conclusion: Compared with CO2 fractional laser, 1,550 nm Er: glass fractional laser therapy provides the significantly better clinical outcomes and fewer side effects in the treatment of striae albae. Limitations: The sample size and follow-up time were limited.

Imaging of Vulva Syringoma With Reflectance Confocal Microscopy.

Objectives: To investigate the application of reflectance confocal microscopy (RCM) imaging in diagnosis of vulva syringoma. Methods: Patients with lesions suspicious of syringoma on vulva were enrolled in the study. After informed consent was taken, the lesions were photographed and imaged with RCM. The features of the lesion in confocal images were then analyzed and compared with the biopsy findings for histology correlation. Results: Eleven cases in total were included in the study. The typical RCM features observed in syringoma are the presence of round to oval high refractive, and relatively monomorphous mass of varying sizes in the superficial and middle dermis, usually surrounded with 1-2 layers of light-dark line structures, which were further confirmed by histological evaluation. Ten cases showed classic features of syringoma and 1 case exhibited milia in RCM images. Conclusions: Syringoma has distinct features in RCM imaging, which correlates well with histological findings, highlighting the potential role of RCM in the diagnosis and differential diagnosis of vulva syringoma.

Novel GNE mutations in three Chinese patients with typical GNE myo-pathy.

GNE myopathy is an adult-onset muscle disorder featuring distal muscle atrophy and weakness. Rimmed vacuoles found in the muscle biopsies and gene mutations lead to the diagnosis of GNE myopathy. We collected clinical information, performed muscle biopsies and genetic testing on three patients. These cases developed typical disease presentations with distal muscle weakness at the ages of 26, 23, and 37 years. Their muscle pathologies revealed rimmed vacuoles. Genetic analysis led to the findings which included, c.1543-1544delGA (p.D515QfsX2)/c.38G>C (p.C13S) compound heterozygous mutation, c.733A>G (p.K245E) homozygous mutation and c.527A>T (p.D176V)/c.1634-1G>C (splicing) ; in which c.1543-1544 del GA (p.D515QfsX2), c.733A>G (p.K245E) and c.1634-1G>C (splicing) are three de novo mutations that have never been reported before. In conclusion, this study broadens the mutational spectrum of the GNE gene.

The Differential Diagnosis of Hypopigmented Mycosis Fungoides and Vitiligo With Reflectance Confocal Microscopy: A Preliminary Study.

Objective: To investigate the role of reflectance confocal microscopy (RCM) in the differential diagnosis of hypopigmented mycosis fungoides (HMF) and vitiligo. Methods: Cases with persistent hypopigmented patches, suspicious of early stage vitiligo, or HMF were imaged with RCM. The melanin contents and inflammatory conditions of the epidermis and superficial dermis of the lesions were compared with the same layers of the adjacent skin, and then, the imaged lesions were biopsied and analyzed by histology. Results: 15 cases were enrolled in this study, and based on the RCM findings, there was just slight or moderate reduction of melanin but no melanin absence in the basal cell layer of HMF lesions. The finding of monomorphous weakly refractile, oval to round cells on the basis of vesicle-like dark space was clearly elucidated in the epidermis of the lesions by RCM, which indicates the Pautrier's microabscesses on histopathology. Among those 15 cases, 13 cases were identified as HMF, and the other two cases were vitiligo, based on RCM findings, which were confirmed by histology analysis. Conclusions: The RCM findings correlated well with histology results in the screening of HMF, which indicates the RCM is an important tool in the early detection and differential diagnosis of HMF.

[Observation on therapeutic effect of filiform fire needle assisted 308 nm excimer laser on vitiligo of different parts].

OBJECTIVE: To compared the therapeutic effect between filiform fire needle assisted 308 nm excimer laser and simple 308 nm excimer laser on vitiligo of different parts. METHODS: Target lesions of 134 patients were divided into an observation group and a control group according to the principle of self-controlled, 201 pieces in each one. In the observation group, filiform fire needle was performed at target lesions. Then target lesions both of the two groups were irradiated with 308 nm excimer laser at the same time. Once every 2 weeks, totally 10 treatments were required. The effective rate and effective rate, color recovery rate and responding time of different parts in the two groups were evaluated 2 weeks after treatment. RESULTS: The effective rate in the observation group was 82.59% (166/201), which was higher than 68.16% (137/201) in the control group (P<0.01). The effective rate of face-neck, trunk, limbs and hand-foot were 90.32%, 81.63%, 81.48% and 58.62% respectively in the observation group, which were higher than 82.80%, 69.39%, 51.85% and 31.03% in the control group (P<0.01, P<0.05). The color recovery rate of different parts in the observation group was higher than the control group, and the effect was faster in the observation group (P<0.01, P<0.05). CONCLUSION: Filiform fire needle as an adjunctive therapy, combined with 308 nm excimer laser are more effective than simple 308 nm excimer laser for vitiligo of different parts. Combination therapy has a shorter responding time, the face-neck has the best effect and hand-foot has poor effect.

A Novel Mutation of Mitochondrial T14709C Causes Myoclonic Epilepsy with Ragged Red Fibers Syndrome in a Chinese Patient.

BACKGROUND: Myoclonic epilepsy with ragged red fibers (MERRF) syndrome is characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged red fibers (RRFs) in the muscle. T-to-C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid (tRNAGlu) gene has previously been associated with maternally inherited diabetes and deafness. However, the association between MERRF and mitochondrial T14709C mutation (m.T14709C) has never been reported before. METHODS: Clinical information of a 17-year-old patient was collected; muscle biopsy and next-generation sequencing (NGS) of whole mitochondrial and neuromuscular disease panel were then conducted. Finally, sanger sequencing was carried out to confirm the mutations. RESULTS: The patient presented a typical MERRF phenotype with muscle weakness, epileptic seizure, clonic episodes, cerebellar ataxia, and spinal scoliosis. Muscle biopsy showed RRFs which indicated abnormal mitochondrial functions. NGS of whole mitochondrial gene revealed m.T14709C mutation, confirmed by Sanger sequencing. CONCLUSION: We present a sporadic patient with typical MERRF presentation carrying the mutation of m.T14709C, which expanded the spectrum of m.T14709C.

Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease.

BACKGROUND: Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations. METHODS: Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted. RESULTS: Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones (c.796C>A, c.1057C>T, c.1201C>A, c.1780C>T, c.1799G>C, c.2051C>A, c.2235dupG), were identified by genetic tests. CONCLUSIONS: The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.

Pathological findings in sporadic inclusion body myositis and GNE myopathy.

OBJECTIVE: The following study compared the pathological findings between sporadic inclusion body myositis (sIBM) and Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase myopathy (GNEM) patients. METHODS: An enzyme histochemistry was used to compare the pathological characteristics between 11 patients with sIBM and 16 patients with GNEM. RESULTS: There were four pathological differences observed: (1) A majority of the rimmed vacuoles found in the sIBM patients resembled cracks, whereas the GNEM patients (P=0.004) had round or oval vacuoles. (2) A majority of the rimmed vacuoles that were located in the periphery of the atrophic muscle fibers of the sIBM patients. The patients with GNEM had a majority of the rimmed vacuoles in the center of the atrophic muscle fibers (P=0.001). (3) The patients with sIBM had basophilic granules in the rimmed vacuoles, which appeared to be fine granules that were sand-like particles. The GNEM patients had coarse granules (P=0.018). (4) The proportion of mononuclear cells invasion of muscle fibers was larger in the sIBM patients than the GNEM patients (P=0.047). The GNEM patients were younger on average than the sIBM patients at the onset of symptoms (P<0.001) and at the diagnosis age (P<0.001). The electromyography (EMG) showed the presence of myogenic lesions in 10 patients with sIBM, both myogenic and neurogenic lesions in one patients with sIBM and myogenic lesions in 16 patients with GNEM. CONCLUSION: There were significant differences in the morphologies of the rimmed vacuoles between sIBM patients and GNEM patients.

Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision: A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles.

BACKGROUND: Myopathies with rimmed vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected. METHODS: A clinical study including family history, obstetric, pediatric, and development history was recorded. Clinical examinations including physical examination, electromyography (EMG), serum creatine kinase (CK), bone X-rays, and brain magnetic resonance imaging (MRI) were performed in this family. Open muscle biopsies were performed on the proband and his mother. To find the causative gene, the whole-exome sequencing was carried out. RESULTS: Disease onset was from adolescence to adulthood, but the affected patients of the third generation presented an earlier onset and more severe clinical manifestations than the older generations. Clinical features were characterized as dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision. However, not every patient manifested all symptoms. Serum CK was mildly elevated and EMG indicated a myopathic pattern. Brain MRI showed cerebellum and brain stem mildly atrophy. Rimmed vacuoles and inclusion bodies were observed in muscle biopsy. The whole-exome sequencing was performed, but the causative gene has not been found. CONCLUSIONS: We reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been found and needs further study.

Treatment of port wine stains with pulsed dye laser: a retrospective study of 848 cases in Shandong Province, People's Republic of China.

BACKGROUND: Currently, 595 nm pulsed dye laser (PDL) therapy is offered as one of the effective treatments of port wine stains (PWSs). However, the efficacy of PDL differs in different populations. OBJECTIVE: The purpose of the study was to investigate the efficacy, and related factors, of 595 nm PDL in the treatment of PWSs in Chinese patients with skin type III to IV. METHODS: A total of 848 cases that were treated with PDL were enrolled and analyzed in this study. An independent dermatologist evaluated these lesions according to the before and after photographs. RESULTS: The response rate (RR) of all the 848 PWS patients was 69.9%, within which the cure rate was 6.3%. The patients aged ≤1 year had the highest RR (93.9%), whereas those treated after age 50 reacted the worst (RR =25%). We analyzed the anatomical distribution of the lesion and found that the temporal region had the highest lesion clearance (RR =75.3%), while the extremities had the lowest clearance (RR =44.5%). Compared with the patients whose lesion size was larger than 80 cm(2), the patients with small lesion size, of 0-20 cm(2), had better clinical effect (RR =73.8% vs 53.2%). The reactions of the patients with hyperplastic lesion were worse than those with red patches (RR =36.4% vs 71.7%). As well, increasing treatment numbers could achieve higher clearance rates (P=0.005). CONCLUSION: The PDL had a relatively high RR but a low clearance rate in Chinese patients with PWS, although the earlier the intervention, the better was the efficacy. The response of PDL was, not only related to the anatomical area, but also, to the lesion size, type of lesion (ie, the presence of existing hyperplastic lesions), and the number of treatment, all of which are essential for the evaluation of therapeutic effect and acquisition of patients consent before treatment.