Analysis of a case of Multiple pterygium syndrome due to a novel variant of CHRNG gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a child with multiple pterygium syndrome (MPS).@*METHODS@#A child with MPS who was treated at the Orthopedics Department of Guangzhou Women and Children's Medical Center Affiliated to Guangzhou Medical University on August 19, 2020 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were also collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing of her parents and bioinformatic analysis.@*RESULTS@#The child, an 11-year-old female, had a complain of "scoliosis found 8 years before and aggravated with unequal shoulder height for 1 year". WES results revealed that she has carried a homozygous c.55+1G>C splice variant of the CHRNG gene, for which both of her parents were heterozygous carriers. By bioinformatic analysis, the c.55+1G>C variant has not been recorded by the CNKI, Wanfang data knowledge service platform and HGMG databases. Analysis with Multain online software suggested that the amino acid encoded by this site is highly conserved among various species. As predicted with the CRYP-SKIP online software, the probability of activation and skipping of the potential splice site in exon 1 caused by this variant is 0.30 and 0.70, respectively. The child was diagnosed with MPS.@*CONCLUSION@#The CHRNG gene c.55+1G>C variant probably underlay the MPS in this patient.

Influence of reactive oxygen species responsive self-assembled nanomicelle loaded with pyroptosis inhibitor on full-thickness skin defects in diabetic rats / 中华烧伤杂志

Objective: To investigate the influence of reactive oxygen species (ROS) responsive self-assembled nanomicelle loaded with pyroptosis inhibitor on full-thickness skin defects in diabetic rats. Methods: Experimental research methods were employed. A nucleotide-binding oligomerization domain (NOD) 1/2 inhibitor (NOD-IN-1) was encapsulated with nanomicelle polyethylene glycol-block-polypropylene sulfide (PEG-b-PPS), and the resulting product was called PEPS@NOD-IN-1. The morphology and hydration particle size of PEG-b-PPS and PEPS@NOD-IN-1 were observed by transmission electron microscope and particle size analyzer, respectively, and the encapsulation rate and drug loading rate of PEPS@NOD-IN-1 to NOD-IN-1 and the cumulative release rate of NOD-IN-1 by PEPS@NOD-IN-1 in phosphate buffer solution (PBS) alone and hydrogen peroxide-containing PBS within 40 h were measured and calculated by microplate reader, and the sample number was 3. Twenty-four male Sprague-Dawley rats aged 6-7 weeks were injected with streptozotocin to induce type 1 diabetes mellitus. Six full-thickness skin defect wounds were made on the back of each rat. The injured rats were divided into PBS group, NOD-IN-1 group, PEG-b-PPS group, and PEPS@NOD-IN-1 group with corresponding treatment according to the random number table, with 6 rats in each group. The wound healing was observed on post injury day (PID) 3, 7, and 12, and the wound healing rate was calculated. The ROS levels in wound tissue were detected by immunofluorescence method on PID 3. On PID 7, the granulation tissue thickness in wound was assessed by hematoxylin-eosin staining, the mRNA expressions of NOD1 and NOD2 were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction, and the protein expressions of NOD1, NOD2, and GSDMD-N terminals were detected by Western blotting. Six wounds from different rats in each group were taken for detection of the above indicators. Wound tissue (3 samples per group) was taken from rats in PBS group and PEPS@NOD-IN-1 group on PID 7, and transcriptome sequencing was performed using high-throughput sequencing technology platform. Differentially expressed genes (DEGs) significantly down-regulated in PEPS@NOD-IN-1 group as compared with PBS group were screened, and the enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed. The DEG heatmap of the NOD-like receptor pathway, a pyroptosis-related pathway, was made. Protein-protein interaction (PPI) analysis of DEGs in heatmap was performed through the STRING database to screen key genes of PEPS@NOD-IN-1 regulating the NOD-like receptor pathway. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and Tukey test. Results: PEG-b-PPS and PEPS@NOD-IN-1 were in spherical structures of uniform size, with hydration particle sizes of (134.2±3.3) and (143.1±2.3) nm, respectively. The encapsulation rate of PEPS@NOD-IN-1 to NOD-IN-1 was (60±5)%, and the drug loading rate was (15±3)%. The release of NOD-IN-1 from PEPS@NOD-IN-1 in PBS alone was slow, and the cumulative release rate at 40 h was only (12.4±2.3)%. The release of NOD-IN-1 from PEPS@NOD-IN-1 in hydrogen peroxide-containing PBS within 10 h was very rapid, and the cumulative release rate at 10 h reached (90.1±3.6)%. On PID 3 and 7, the wounds of rats in the four groups were gradually healed, and the healing in PEPS@NOD-IN-1 group was better than that in the other three groups. On PID 12, the wound scab area in PBS group was large, the wound epithelialization in NOD-IN-1 group and PEG-b-PPS group was obvious, and the wound in PEPS@NOD-IN-1 group was close to complete epithelialization. Compared with those in PBS group, NOD-IN-1 group, and PEG-b-PPS group, the wound healing rates on PID 7 and 12 in PEPS@NOD-IN-1 group were significantly increased (P<0.05), the level of ROS in wound tissue on PID 3 was significantly decreased (P<0.05), the thickness of granulation tissue in wound on PID 7 was significantly thickened (P<0.05), and the mRNA expressions of NOD1 and NOD2 and the protein expressions of NOD1, NOD2, and GSDMD-N terminals in wound tissue on PID 7 were significantly decreased (P<0.05). KEGG pathway analysis showed that DEGs significantly down-regulated in PEPS@NOD-IN-1 group as compared with PBS group were significantly enriched in NOD-like receptors, hypoxia-inducible factors, mitogen-activated protein kinases, and tumor necrosis factor (TNF) pathways. In the DEG heatmap of NOD-like receptor pathway, the genes regulating pyroptosis mainly involved NOD1, NOD2, NOD-like receptor thermoprotein domain-related protein 3, Jun, signal transduction and transcriptional activator 1 (STAT1), TNF-α-induced protein 3. The PPI results showed that NOD1, NOD2, and STAT1 were the key genes of PEPS@NOD-IN-1 regulating the NOD-like receptor pathway. Conclusions: PEPS@NOD-IN-1 can down-regulate the level of local ROS in wounds and the expression of NOD1, NOD2, and GSDMD-N terminals, the key regulators of pyroptosis, thereby promoting the repair of full-thickness skin defect wounds in diabetic rats. PEPS@NOD-IN-1 can also significantly down-regulate the pyroptosis, inflammation, and hypoxia-related pathways of wounds, and regulate NOD-like receptor pathways by down-regulating key genes NOD1, NOD2, and STAT1.

Treatments of palpebral congenital melanocytic nevus: a systematic review

Purpose: Palpebral congenital melanocytic nevi (PCMN) is a rare congenital skin lesion affecting the eyelids that can lead to cosmetic and psychological concerns and potential health risks such as malignancy. Several authors have analyzed therapeutical strategies to treat PCMN. However, there was no consensus in the literature. This systematic review aimed to evaluate the effectiveness, safety, and success of treatments of PCMN. Methods: We conducted a systematic review following PRISMA guidelines from October 2022 to April 2023. We included all types of study designs that described or compared PCMN treatments and interventions, as well as histology, recurrence, adverse events, patient satisfaction, and malignant transformation. The search strategy was based on specific search words through the following databases: PubMed, Embase, Latin American and Caribbean Health Sciences Literature (Lilacs), Web of Science, and Scopus. Ongoing studies and gray literature studies were included. Results: We analyzed 25 case reports with 148 participants. The effectiveness, success, and satisfaction with various treatments for PCMN depend on the specific treatment method and the individual patient's case. Conclusions: Most of the studies showed that surgical procedures (exeresis) are able to treat PCMN in the eyelid. The variability in outcomes emphasizes the importance of further research to better understand the most effective and safe approaches for treating congenital melanocytic nevi.

Effects of in situ cross-linked graphene oxide-containing gelatin methacrylate anhydride hydrogel on wound vascularization of full-thickness skin defect in mice / 中华烧伤杂志

Objective: To prepare graphene oxide (GO)-containing gelatin methacrylate anhydride (GelMA) hydrogel and to investigate the effects of in situ photopolymerized GO-GelMA composite hydrogel in wound vascularization of full-thickness skin defect in mice. Methods: The experimental study method was used. The 50 μL of 0.2 mg/mL GO solution was evenly applied onto the conductive gel, and the structure and size of GO were observed under field emission scanning electron microscope after drying. Human skin fibroblasts (HSFs) were divided into 0 μg/mL GO (without GO solution, the same as below) group, 0.1 μg/mL GO group, 1.0 μg/mL GO group, 5.0 μg/mL GO group, and 10.0 μg/mL GO group treated with GO of the corresponding final mass concentration, and the absorbance value was detected using a microplate analyzer after 48 h of culture to reflect the proliferation activity of cells (n=6). HSFs and human umbilical vein vascular endothelial cells (HUVECs) were divided into 0 μg/mL GO group, 0.1 μg/mL GO group, 1.0 μg/mL GO group, and 5.0 μg/mL GO group treated with GO of the corresponding final mass concentration, and the migration rates of HSFs at 24 and 36 h after scratching (n=5) and HUVECs at 12 h after scratching (n=3) were detected by scratch test, and the level of vascular endothelial growth factor (VEGF) secreted by HSFs after 4, 6, and 8 h of culture was detected by enzyme-linked immunosorbent assay method (n=3). The prepared GO-GelMA composite hydrogels containing GO of the corresponding final mass concentration were set as 0 μg/mL GO composite hydrogel group, 0.1 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group to observe their properties before and after cross-linking, and to detect the release of GO after soaking with phosphate buffer solution for 3 and 7 d (n=3). The full-thickness skin defect wounds were made on the back of 16 6-week-old female C57BL/6 mice. The mice treated with in situ cross-linked GO-GelMA composite hydrogel containing GO of the corresponding final mass concentration were divided into 0 μg/mL GO composite hydrogel group, 0.1 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group according to the random number table, with 4 mice in each group. The general condition of wound was observed and the wound healing rate was calculated on 3, 7, and 14 d of treatment, the wound blood perfusion was detected by laser Doppler flowmetry on 3, 7, and 14 d of treatment and the mean perfusion unit (MPU) ratio was calculated, and the wound vascularization on 7 d of treatment was observed after hematoxylin-eosin staining and the vascular density was calculated (n=3). The wound tissue of mice in 0 μg/mL GO composite hydrogel group and 0.1 μg/mL GO composite hydrogel group on 7 d of treatment was collected to observe the relationship between the distribution of GO and neovascularization by hematoxylin-eosin staining (n=3) and the expression of VEGF by immunohistochemical staining. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and Tukey's method. Results: GO had a multilayered lamellar structure with the width of about 20 μm and the length of about 50 μm. The absorbance value of HSFs in 10.0 μg/mL GO group was significantly lower than that in 0 μg/mL GO group after 48 h of culture (q=7.64, P<0.01). At 24 h after scratching, the migration rates of HSFs were similar in the four groups (P>0.05); at 36 h after scratching, the migration rate of HSFs in 0.1 μg/mL GO group was significantly higher than that in 0 μg/mL GO group, 1.0 μg/mL GO group, and 5.0 μg/mL GO group (with q values of 7.48, 10.81, and 10.20, respectively, P<0.01). At 12 h after scratching, the migration rate of HUVECs in 0.1 μg/mL GO group was significantly higher than that in 0 μg/mL GO group, 1.0 μg/mL GO group, and 5.0 μg/mL GO group (with q values of 7.11, 8.99, and 14.92, respectively, P<0.01), and the migration rate of HUVECs in 5.0 μg/mL GO group was significantly lower than that in 0 μg/mL GO group and 1.0 μg/mL GO group (with q values of 7.81 and 5.33, respectively, P<0.05 or P<0.01 ). At 4 and 6 h of culture, the VEGF expressions of HSFs in the four groups were similar (P>0.05); at 8 h of culture, the VEGF expression of HSFs in 0.1 μg/mL GO group was significantly higher than that in 0 μg/mL GO group and 5.0 μg/mL GO group (with q values of 4.75 and 4.48, respectively, P<0.05). The GO-GelMA composite hydrogels in the four groups were all red liquid before cross-linking, which turned to light yellow gel after cross-linking, with no significant difference in fluidity. The GO in the GO-GelMA composite hydrogel of 0 μg/mL GO composite hydrogel group had no release of GO at all time points; the GO in the GO-GelMA composite hydrogels of the other 3 groups was partially released on 3 d of soaking, and all the GO was released on 7 d of soaking. From 3 to 14 d of treatment, the wounds of mice in the 4 groups were covered with hydrogel dressings, kept moist, and gradually healed. On 3, 7, and 14 d of treatment, the wound healing rates of mice in the four groups were similar (P>0.05). On 3 d of treatment, the MPU ratio of wound of mice in 0.1 μg/mL GO composite hydrogel group was significantly higher than that in 0 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group (with q values of 10.70, 11.83, and 10.65, respectively, P<0.05 or P<0.01). On 7 and 14 d of treatment, the MPU ratios of wound of mice in the four groups were similar (P>0.05). The MPU ratio of wound of mice in 0.1 μg/mL GO composite hydrogel group on 7 d of treatment was significantly lower than that on 3 d of treatment (q=14.38, P<0.05), and that on 14 d of treatment was significantly lower than that on 7 d of treatment (q=27.78, P<0.01). On 7 d of treatment, the neovascular density of wound of mice on 7 d of treatment was 120.7±4.1 per 200 times of visual field, which was significantly higher than 61.7±1.3, 77.7±10.2, and 99.0±7.9 per 200 times of visual field in 0 μg/mL GO composite hydrogel group, 1.0 μg/mL GO composite hydrogel group, and 5.0 μg/mL GO composite hydrogel group (with q values of 12.88, 7.79, and 6.70, respectively, P<0.01), and the neovascular density of wound of mice in 1.0 μg/mL GO composite hydrogel group and 5.0 μg/mL GO composite hydrogel group was significantly higher than that in 0 μg/mL GO composite hydrogel group (with q values of 5.10 and 6.19, respectively, P<0.05). On 7 d of treatment, cluster of new blood vessels in wound of mice in 0.1 μg/mL GO composite hydrogel group was significantly more than that in 0 μg/mL GO composite hydrogel group, and the new blood vessels were clustered near the GO; a large amount of VEGF was expressed in wound of mice in 0.1 μg/mL GO composite hydrogel group in the distribution area of GO and new blood vessels. Conclusions: GO with mass concentration lower than 10.0 μg/mL had no adverse effect on proliferation activity of HSFs, and GO of 0.1 μg/mL can promote the migration of HSFs and HUVECs, and can promote the secretion of VEGF in HSFs. In situ photopolymerized of GO-GelMA composite hydrogel dressing can promote the wound neovascularization of full-thickness skin defect in mice and increase wound blood perfusion in the early stage, with GO showing an enrichment effect on angiogenesis, and the mechanism may be related to the role of GO in promoting the secretion of VEGF by wound cells.

Feasibility study on the preparation of novel negative pressure materials for constructing new matrix of full-thickness skin defect wounds in rats / 中华烧伤杂志

Objective: To explore the feasibility on the preparation of novel negative pressure materials for constructing new matrix of full-thickness skin defect wounds in rats. Methods: The experimental research method was applied. The microstructure of polyurethane foam dressing which was commonly used in negative pressure treatment was observed under scanning electron microscope, and its pore diameter was detected (n=5). Polycaprolactone (PCL) and polybutylene succinate (PBS) were used respectively as raw materials for the preparation of PCL and PBS negative pressure materials by melt spinning technology, with the measured pore diameter of polyurethane foam dressing as the spinning spacing at the spinning rates of 15, 25, and 35 mm/s, respectively. The microstructures of the prepared negative pressure materials were observed under scanning electron microscope, and their fiber diameters were measured. The tensile strength and tensile modulus of the prepared negative pressure materials and polyurethane foam dressing were measured by tensile testing machine and composite testing machine, respectively (n=5), to screen the spinning rate for subsequent preparation of negative pressure materials. Human skin fibroblasts (Fbs) in logarithmic growth phase were co-cultured with PCL negative pressure material and PBS negative pressure material prepared at the selected spinning rate, respectively. After 1, 4, and 7 day (s) of co-culture, the cell activity and adhesion in the materials was detected by living/dead cells detection kit, and the cell proliferation level in the materials was detected by cell counting kit 8 method (n=5). A full-thickness skin defect wound was prepared on the back of 18 5-6 weeks old Sprague-Dawley rats (gender unlimited). Immediately after injury, the injured rats were divided into PCL+polyurethane group, PBS+polyurethane group, and polyurethane alone group according to the random number table (with 6 rats in each group). The wounds were covered with materials containing corresponding component and performed with continuous negative pressure suction at the negative pressure of -16.7 kPa. The wound tissue along with materials directly contacted to the wound (hereinafter referred to as wound specimens) were collected from 3 rats in each group after 7 and 14 days of negative pressure treatment (NPT), respectively. The growth of granulation tissue and the attachment of material to wound surface were observed after hematoxylin-eosin staining, the collagen fiber deposition was observed after Masson staining, and CD34 and interleukin-6 (IL-6) positive cells were detected and counted by immunohistochemical staining. Data were statistically analyzed with one-way analysis of variance, analysis of variance for factorial design, least significant difference-t test, Kruskal-Wallis H test, Mann-Whitney U test, and Bonferroni correction. Results: The microstructure of polyurethane foam dressing was loose and porous, with the pore diameter of (815±182) μm. The spinning spacing for the subsequent negative pressure material was set as 800 μm. The microstructures of PBS negative pressure material and PCL negative pressure material were regular, with vertically interconnected layers and continuous fibers in even thickness, but the fibers of PBS negative pressure material were straighter than those of PCL negative pressure material. There was no obvious difference in the microstructure of negative pressure materials prepared from the same raw material at different spinning rates. The fiber diameters of PCL negative pressure materials prepared at three spinning rates were similar (P>0.05). The fiber diameters of PBS negative pressure materials prepared at spinning rates of 25 mm/s and 35 mm/s were significantly smaller than the fiber diameter of PBS negative pressure material prepared at the spinning rate of 15 mm/s (with t values of 4.99 and 6.40, respectively, P<0.01). Both the tensile strength and tensile modulus of PCL negative pressure materials prepared at three spinning rates were similar (P>0.05). The tensile strength of PBS negative pressure materials prepared at spinning rates of 15 mm/s and 25 mm/s was significantly lower than that of PBS negative pressure materials prepared at the spinning rate of 35 mm/s (with t values of 9.20 and 8.92, respectively, P<0.01), and the tensile modulus was significantly lower than that of PBS negative pressure materials prepared at the spinning rate of 35 mm/s (with t values of 2.58 and 2.47, respectively, P<0.05). Subsequently, PCL negative pressure material was prepared at the spinning rate of 35 mm/s, and PBS negative pressure material was prepared at the spinning rate of 15 mm/s. After 1, 4, and 7 day (s) of co-culture, the number of human skin Fbs that adhered to PCL negative pressure material and PBS negative pressure material increased with time, and there was no significant difference between the two materials. After 1 and 7 day (s) of co-culture, the proliferation levels of human skin Fbs between the two negative pressure materials were similar (P>0.05). After being co-cultured for 4 days, the proliferation level of human skin Fbs in PBS negative pressure material was significantly higher than that in PCL negative pressure material (t=6.37, P<0.01). After 7 days of NPT, the materials were clearly identifiable and a small amount of collagen fibers were also observed in the wound specimens of rats in the three groups; a small amount of granulation tissue was observed in the wound specimens of rats in polyurethane alone group. After 14 days of NPT, a large number of granulation tissue and collagen fibers were observed in the wound specimens of rats in the three groups; the materials and wound tissue in the wound specimens of rats in PCL+polyurethane group could not be clearly distinguished. After 7 and 14 days of NPT, the collagen fibers in the wound specimens of rats in polyurethane alone group were denser than those in the other two groups. After 7 days of NPT, the number of CD34 positive cells in the wound specimens of rats in PBS+polyurethane group was 14.8±3.6 per 400 times visual field, which was significantly less than 27.8±9.1 in polyurethane alone group (t=3.06, P<0.05); the number of IL-6 positive cells was 60 (49, 72), which was significantly more than 44 (38, 50) in polyurethane alone group (Z=2.41, P<0.05). After 14 days of NPT, the number of IL-6 positive cells in the wound specimens of rats in PBS+polyurethane group was 19 (12, 28) per 400 times visual field, which was significantly more than 3 (1, 10) in PCL+polyurethane group and 9 (2, 13) in polyurethane alone group (with Z values of 2.61 and 2.40, respectively, P<0.05). Conclusions: The prepared PCL negative pressure material and PBS negative pressure material have good biocompatibility, and can successfully construct the new matrix of full-thickness skin defect wounds in rats. PCL negative pressure material is better than PBS negative pressure material in general.

Investigation on the growth factor regulatory network of dermal fibroblasts in mouse full-thickness skin defect wounds based on single-cell RNA sequencing / 中华烧伤杂志

Objective: To explore the heterogeneity and growth factor regulatory network of dermal fibroblasts (dFbs) in mouse full-thickness skin defect wounds based on single-cell RNA sequencing. Methods: The experimental research methods were adopted. The normal skin tissue from 5 healthy 8-week-old male C57BL/6 mice (the same mouse age, sex, and strain below) was harvested, and the wound tissue of another 5 mice with full-thickness skin defect on the back was harvested on post injury day (PID) 7. The cell suspension was obtained by digesting the tissue with collagenase D and DNase Ⅰ, sequencing library was constructed using 10x Genomics platform, and single-cell RNA sequencing was performed by Illumina Novaseq6000 sequencer. The gene expression matrices of cells in the two kinds of tissue were obtained by analysis of Seurat 3.0 program of software R4.1.1, and two-dimensional tSNE plots classified by cell group, cell source, and gene labeling of major cells in skin were used for visual display. According to the existing literature and the CellMarker database searching, the expression of marker genes in the gene expression matrices of cells in the two kinds of tissue was analyzed, and each cell group was numbered and defined. The gene expression matrices and cell clustering information were introduced into CellChat 1.1.3 program of software R4.1.1 to analyze the intercellular communication in the two kinds of tissue and the intercellular communication involving vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and fibroblast growth factor (FGF) signal pathways in the wound tissue, the relative contribution of each pair of FGF subtypes and FGF receptor (FGFR) subtypes (hereinafter referred to as FGF ligand receptor pairs) to FGF signal network in the two kinds of tissue, and the intercellular communication in the signal pathway of FGF ligand receptor pairs with the top 2 relative contributions in the two kinds of tissue. The normal skin tissue from one healthy mouse was harvested, and the wound tissue of one mouse with full-thickness skin defect on the back was harvested on PID 7. The multiple immunofluorescence staining was performed to detect the expression and distribution of FGF7 protein and its co-localized expression with dipeptidyl peptidase 4 (DPP4), stem cell antigen 1 (SCA1), smooth muscle actin (SMA), and PDGF receptor α (PDGFRα) protein. Results: Both the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7 contained 25 cell groups, but the numbers of cells in each cell group between the two kinds of tissue were different. Genes PDGFRα, platelet endothelial cell adhesion molecule 1, lymphatic endothelial hyaluronic acid receptor 1, receptor protein tyrosine phosphatase C, keratin 10, and keratin 79 all had distinct distributions on two-dimensional tSNE plots, indicating specific cell groups respectively. The 25 cell groups were numbered by C0-C24 and divided into 9 dFb subgroups and 16 non-dFb groups. dFb subgroups included C0 as interstitial progenitor cells, C5 as adipose precursor cells, and C13 as contractile muscle cells related fibroblasts, etc. Non-dFb group included C3 as neutrophils, C8 as T cells, and C18 as erythrocytes, etc. Compared with that of the normal skin tissue of healthy mice, the intercellular communication in the wound tissue of full-thickness skin defected mice on PID 7 was more and denser, and the top 3 cell groups in intercellular communication intensity were dFb subgroups C0, C1, and C2, of which all communicated with other cell groups in the wound tissue. In the wound tissue of full-thickness skin defected mice on PID 7, VEGF signals were mainly sent by the dFb subgroup C0 and received by vascular related cell groups C19 and C21, PDGF signals were mainly sent by peripheral cells C14 and received by multiple dFb subgroups, EGF signals were mainly sent by keratinocyte subgroups C9 and C11 and received by the dFb subgroup C0, and the main sender and receiver of FGF signals were the dFb subgroup C6. In the relative contribution rank of FGF ligand receptor pairs to FGF signal network in the normal skin tissue of healthy mice and the wound tissue of full-thickness skin defected mice on PID 7, FGF7-FGFR1 was the top 1, and FGF7-FGFR2 or FGF10-FGFR1 was in the second place, respectively; compared with those in the normal skin tissue, there was more intercellular communication in FGF7-FGFR1 signal pathway, while the intercellular communication in FGF7-FGFR2 and FGF10-FGFR1 signal pathways decreased slightly or did not change significantly in the wound tissue; the intercellular communication in FGF7-FGFR1 signal pathway in the wound tissue was stronger than that in FGF7-FGFR2 or FGF10-FGFR1 signal pathway; in the two kinds of tissue, FGF7 signal was mainly sent by dFb subgroups C0, C1, and C2, and received by dFb subgroups C6 and C7. Compared with that in the normal skin tissue of healthy mouse, the expression of FGF7 protein was higher in the wound tissue of full-thickness skin defected mouse on PID 7; in the normal skin tissue, FGF7 protein was mainly expressed in the skin interstitium and also expressed in the white adipose tissue near the dermis layer; in the two kinds of tissue, FGF7 protein was co-localized with DPP4 and SCA1 proteins and expressed in the skin interstitium, co-localized with PDGFRα protein and expressed in dFbs, but was not co-localized with SMA protein, with more co-localized expression of FGF7 in the wound tissue than that in the normal skin tissue. Conclusions: In the process of wound healing of mouse full-thickness skin defect wound, dFbs are highly heterogeneous, act as potential major secretory or receiving cell populations of a variety of growth factors, and have a close and complex relationship with the growth factor signal pathways. FGF7-FGFR1 signal pathway is the main FGF signal pathway in the process of wound healing, which targets and regulates multiple dFb subgroups.

Papilomatosis confluente y reticulada de Gougerot-Carteaud / Confluent and reticulated papillomatosis of Gougerot-Carteaud

La papilomatosis confluente y reticulada es una dermatosis infrecuente, benigna, de curso crónico y etiopatogenia desconocida. Actualmente, se acepta que se debe a un trastorno de la queratinización. Se caracteriza por máculas y pápulas hiperpigmentadas, que coalescen en el centro y adoptan un patrón reticular en la periferia. Se la puede confundir con otras patologías, como la pitiriasis versicolor y la acantosis nigricans. Con la administración de minociclina por vía oral suelen obtenerse excelentes resultados. Se comunica el caso de un paciente con diagnóstico de papilomatosis confluente y reticulada. Se describen sus características clínicas, criterios diagnósticos y trata-miento instaurado.

Confluent and reticulated papillomatosis is an infrequent, benign dermatosis of chronic course and unknown etiopathogenesis. Currently it is accepted that this dermatosis is due to a keratinization disorder. It is characterized by hyperpigmented macules and papules that coalesce in the center and adopt a reticular pattern in the periphery. It can be confused with other pathologies such as pityriasis versicolor and acanthosis nigricans. Oral minocycline usually shows excellent results. The present work reports a case of a patient with a diagnosis of confluent and retic-ulated papillomatosis, describing its clinical characteristics, diagnostic criteria and established treatment.

Phenotype and genetic variant analysis of seven pedigrees affected with blepharophimosis syndrome / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical manifestations and gene variants of patients with blepharophimosis, ptosis and epicanthus inversus syndrome (BPES).@*METHODS@#Clinical data of 7 pedigrees affected with BPES were collected, and genomic DNA was extracted from peripheral blood samples of the probands and their relatives. All exons of the FOXL2 gene were subjected to Sanger sequencing. Those with negative findings were further screened by targeted capture and next generation sequencing (NGS) and microarray analysis. Pathogenicity of candidate variants were predicted by search of PubMed and related databases, and the impact of the variants was interpreted by protein prediction software. Diagnosis was confirmed by clinical phenotype, medical history and mutation analysis.@*RESULTS@#A pathogenic variant was identified in six of the 7 pedigrees, which included four known pathogenic variants and one novel FOXL2 c.299dupA variant. A heterozygous 3q22.3q23 deletion, which encompassed the FOXL2 gene, was identified in another pedigree.As predicted, the c.299dupA frameshift mutation of FOXL2 gene can lead to the premature termination of protein translation, which is pathogenic.@*CONCLUSION@#A novel and 5 known pathogenic variants have been identified in six pedigrees affected with BPES by the combined Sanger sequencing, target capture NGS and microarray analysis. Above findings have enabled genetic counseling and prenatal diagnosis for these pedigrees.

Inverse klippel-trenaunay syndrome / Síndrome de klippel-trenaunay inverso

ABSTRACT Objective: To report a rare case of inverse Kipplel-Trenaunay. Case description: A 16-year-old girl with a grayish-depressed plaque on her left thigh. Angioresonance showed a vascular malformation affecting the skin and subcutaneous tissue. Comments: Inverse Klippel-Trenaunay is a Klippel-Trenaunay syndrome variation in which there are capillary and venous malformations associated to hypotrophy or shortening of the affected limb. Modifications on the limb's length or width result from alterations in bones, muscles, or subcutaneous tissues. It has few described cases. Further clinical and molecular studies must be performed for a proper understanding.

RESUMO Objetivo: Relatar um caso raro de Klippel-Trenaunay inverso. Descrição do caso: Menina de 16 anos com placa deprimida acinzentada na coxa esquerda, evidenciando-se, por meio de angioressonância, uma malformação vascular, acometendo a pele e tecidos subcutâneos. Comentários: Klippel-Trenaunay inverso é uma variante da síndrome de Klippel-Trenaunay em que há malformação capilar e venosa associada à hipotrofia ou encurtamento do membro afetado. Pode envolver acometimento ósseo, muscular ou subcutâneo, modificando o comprimento ou a circunferência do membro. Há poucos casos descritos, e mais estudos clínicos e moleculares precisam ser realizados para seu correto entendimento.

Durometry as an alternative tool to the modified Rodnans skin score in the assessment of diffuse systemic sclerosis patients: a cross-sectional study

Abstract Background The reproducibility and reliability of the modified Rodnan's Skin Score (mRSS) are debated due to investigator-related subjectivity. Here, we evaluate if durometry correlates with mRSS in patients with diffuse systemic sclerosis (SSc). Methods This cross-sectional study was conducted from December 2018 to June 2019, including 58 diffuse SSc patients. Two certified researchers, blind to each other's scores, performed the mRSS, followed by durometry at 17 predefined skin sites. For durometry and mRSS, individual scores per skin site were registered. Durometry and mRSS results measured by each researcher, as well as scores from different researchers, were compared. Skin thickness measurements from forearm skin biopsies were available in a subset of the patients, for comparisons. Statistical analyses included Cohen's Kappa Coefficient, Intraclass Correlation Coefficient, Kendall's Coefficient and Spearman's test. Results Mean (standard deviation, SD) patient age was 44.8 (12.9) years, and 88% were female. Inter-rater agreement varied from 0.88 to 0.99 (Intraclass correlation coefficient) for durometry, and 0.54 to 0.79 (Cohen's Kappa coefficient) for mRSS, according to the specific evaluated sites. When data were compared with skin thickness assessed in forearm biopsies, durometry correlated better with skin thickness than mRSS. Conclusion Durometry may be considered as an alternative method to quantify skin involvement in patients with diffuse SSc. The strong inter-rater agreement suggests that the method may be useful for the assessment of patients by multiple researchers, as in clinical trials.(AU)

Clinical analysis, diagnosis, and treatment of a 48-year-old female Filipino with Riehl melanosis

@#INTRODUCTION: Pigmented contact dermatitis (PCD) is characterized by non-eczematous pigmentation associated with contact sensitizers, usually without any active or preceding pruritus and erythema. PCD was first described by Riehl, who identified patients with brown to gray facial pigmentation concentrated on the face most commonly associated with sensitizing chemical such as cosmetics, fragrances, and textiles. CASE REPORT: This is a case of a 48-year-old female Filipino who presents with blue-grey to brown patches on the forehead of 1-year duration with no significant pathologic history. Clinical examination, dermoscopy and histology were consistent with a variant of pigmented contact dermatitis known as Riehl melanosis. Since anamnesis was unremarkable, patch testing was done to identify the contact allergen triggering the symptom. Results obtained a positive reaction to nickel, potassium dichromate, and textile dye. CONCLUSION:Treatment includes the elimination of trigger factors, hence the importance of patch testing in the investigation of its cause. Alongside adequate photoprotection, a combination treatment of 1,064 nm Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, 20% tricholoacetic acid (TCA) peel and oral retinoids, were found safe and effective in the management of facial melanosis. Three-dimensional imaging and dermoscopy were utilized to obtain a more standard and objective pre- and post-treatment comparison.

Ictiose congênita de Arlequim: relato de um caso / Cogenital ichthyosis of Harlequin: report of a case

Relato de caso: apresentamos um caso de diagnóstico ecográfico pré-natal de ictiose de Arlequim, que evoluiu com óbito intrauterino. Conclusão: esse distúrbio caracteriza-se por um neonato envolto por uma membrana espessa de material córneo com fissuras generalizadas, comprometendo as funções básicas da pele e predispondo o recém-nascido a infecções e a alterações metabólicas. Com prognóstico desfavorável, o diagnóstico precoce e o tratamento de suporte visam aumentar a sobrevida e melhorar a qualidade de vida ao neonato.

Case report: we present a case of prenatal ultrasound diagnosis of ichthyosis of Harlequin, which evolved with intrauterine decease. Conclusion: this disorder is characterized by a neonate wrapped in a thick membrane off horny material with generalized fissures that compromise the basic functions of the skin, predisposing the newborn to infections and metabolic alterations. With a reserved prognosis, early diagnosis and supportive care aim to increase survival and improve the quality of life of the newborn.

Comparação do Escore de Rodnan modificado e durômetro em pacientes com esclerose sistêmica difusa / Comparison of the modified Rodnan skin score and durometer in patients with diffuse systemic sclerosis

esclerose sistêmica é uma enfermidade autoimune, causadora de danos vasculares e fibroses. É dentre as doenças de sistema conjuntivo, bem conhecida, devido à alta mortalidade, principalmente pelas causas pulmonares e cardíacas. Para a avaliação do tecido cutâneo de portadores de esclerose sistêmica é utilizado o Escore de Rodnan Modificado, que consiste no pregueamento da pele, porém esta avaliação pode ser subjetiva, devido às limitações na mensuração do escore, tanto pela variabilidade do profissional, quanto pela percepção na aferição do procedimento. Na busca de uma forma de avaliação embasada em evidências científicas, propôs-se este estudo para subsidiar a aferição objetiva do tecido cutâneo. O objetivo do estudo foi correlacionar os Escores de Rodnan Modificados e as medidas do aparelho durômetro, obtidos por dois pesquisadores distintos, em pacientes com esclerose sistêmica difusa. Trata-se de um estudo analítico e transversal, realizado com pacientes maiores de 16 anos, de ambos os sexos. A amostra desta pesquisa foi constituída por 58 pacientes, com maior predominância entre pacientes com cor da pele branca. Houve correlação discretamente moderada e moderada entre as avaliações das medidas obtidas com o Escore de Rodnan Modificado e também com o aparelho durômetro realizadas pelos pesquisadores 1 e 2. A concordância entre os pesquisadores foi avaliada com Coeficiente de Kappa para Escore de Rodnan Modificado e Coeficiente de Correlação Interclasse para o aparelho durômetro, com melhores resultados para as medidas obtidas com este aparelho. Houve também forte correlação positiva entre o escore de Rodnan modificado, média durômetro total e espessura da derme. Portanto, concluí-se que o aparelho durômetro poderá ser utilizado como método de avaliação do tecido cutâneo em pacientes com esclerose sistêmica difusa. Além disso, é um aparelho de fácil manuseio, o que possibilita os demais integrantes da equipe de saúde realizarem as medidas

Systemic sclerosis is an autoimmune disease that causes vascular damage and fibrosis. It belongs to the group of connective tissue diseases and is well known because of the high mortality associated with it, especially as a consequence of lung and heart problems. The modified Rodnan skin score is used to evaluate the skin tissue of people with systemic sclerosis. It consists of assessing skin wrinkling, but it can be subjective because of the limitations in the process of obtaining the score, both because of the variability of the professionals who perform the procedure and the perception during the measurement. The present study was proposed to provide resources to objectively measure skin tissue, as an attempt to design an evaluation form based on scientific evidence. Its objective was to correlate modified Rodnan skin scores and measures obtained with durometers collected by two different researchers in patients with diffuse systemic sclerosis. It is an analytical and cross-sectional study, carried out with patients at least 16 years old, of both genders. The sample was made up of 58 patients, with a predominance of people with white skin. There were discreetly moderate and moderate correlations between the evaluations of the measurements obtained with the modified Rodnan score and the durometer equipment carried out by researchers 1 and 2. Agreement between the researchers was assessed by using the kappa coefficient for the modified Rodnan skin score and the interclass correlation coefficient for the durometer equipment, with better results for the measurements collected with the latter method. There was a strong positive correlation between the modified Rodnan skin score, the total average obtained with the durometer, and dermis thickness. It was concluded that durometers can be used as a method to evaluate the skin tissue in patients with diffuse systemic sclerosis. The equipment is easy to handle, which allows other members of the health team to carry out the measurements

Erupción polimorfa durante el puerperio inmediato / Polymorphic eruption during the postpartum period / Erupção polimórfica durante o puerpério imediato

Introducción. En el embarazo, las dermatosis afectan a menos del 20 % de las gestantes y representan un grupo heterogéneo de afecciones cutáneas, con una forma variada de presentación y evolución. El objetivo es presentar un caso de erupción polimorfa de inicio durante el puerperio, con una breve revisión de la literatura en torno a la patología y su tratamiento. Reporte de caso. Se presenta el caso de una paciente de 38 años en puerperio de su primera gestación, quien debutó con un cuadro clínico de erupción cutánea y prurito que inició en la zona abdominal y se extendió hacia los miembros inferiores. Las lesiones estaban constituidas por pápulas eritematosas que confluían hasta formar placas. Se diagnosticó con erupción polimorfa del embarazo y se dio manejo con antihistamínicos logrando la resolución de la patología. Discusión. La erupción polimórfica del embarazo es un trastorno inflamatorio benigno de la piel. Inicia con la aparición de pápulas pruriginosas que confluyen hasta formar placas eritematosas, que aparecen primero en el abdomen con excepción de la zona umbilical y parten, generalmente, de las estrías y se diseminan a las extremidades. El tratamiento consiste en la utilización de emolientes y antihistamínicos para el control de las lesiones y el prurito. Conclusiones. Aunque se trata de una patología benigna y autolimitada, es importante llegar al diagnóstico correcto e iniciar un manejo médico adecuado ya que síntomas como el prurito pueden generar lesiones por rascado que suelen infectarse y comprometer el estado de salud de las pacientes. Cómo citar: Picón-Jaimes YA, Orozco-Chinome JE, Mejía-Antolínez LA, Garcés-Salamanca CT. Erupción polimorfa durante el puerperio inmediato. MedUNAB. 2019;22(1):64-70. doi:10.29375/01237047.3461

Introduction. During pregnancy, at least 20% of the expectant mothers are affected by several forms of dermatosis, which involve a heterogeneous group of skin conditions with a variety of manifestations and evolution. The objective is to present a case of initial polymorphic eruption during the postpartum period with a brief review of the literature related to the pathology and its treatment. Case report. We present the case of a 38 year-old postpartum patient in her first pregnancy, who exhibited a clinical case of skin eruption and pruritus that started in the abdominal area and extended to the lower limbs. The lesions consisted of erythematous papules that clustered together to form plaques. She was diagnosed with polymorphic eruption of pregnancy and was treated with antihistamines, which resolved the pathology. Discussion. Polymorphic eruption of pregnancy is a benign inflammatory disorder of the skin It starts with the appearance of pruritic papules that cluster together to form erythematous plaques that initially appear in the abdomen (with the exception of the umbilical area) and generally start at the stretch marks and disseminate to the extremities. Treatment consists of the use of emollients and antihistamines to control the lesions and the pruritus. Conclusions. Although this is a benign, self-limiting condition, it is important to reach a correct diagnosis and initiate adequate medical treatment, as symptoms like pruritus can generate lesions from scratching that usually become infected and compromiso the patients' health. Cómo citar: Picón-Jaimes YA, Orozco-Chinome JE, Mejía-Antolínez LA, Garcés-Salamanca CT. Erupción polimorfa durante el puerperio inmediato. MedUNAB. 2019;22(1):64-70. doi:10.29375/01237047.3461

Introdução. Na gravidez, as dermatoses afetam menos de 20% das gestantes e representam um grupo heterogêneo de condições da pele, com uma forma variada de apresentação e evolução. O objetivo é apresentar um caso de erupção polimorfa que iniciou durante o puerpério, com uma breve revisão de literatura sobre a patologia e seu tratamento. Relato de caso. Apresentamos o caso de uma paciente de 38 anos no puerpério de sua primeira gestação, quem desenvolveu um quadro clínico de erupção cutânea e prurido que iniciou na região abdominal e espalhou-se nos membros inferiores. As lesões estavam constituídas por pápulas eritematosas que confluíam até formar placas. Foi diagnosticada com erupção polimórfica da gravidez e recebeu anti-histamínicos, conseguindo a resolução da patologia. Discussão. A erupção polimórfica da gravidez é uma doença inflamatória benigna da pele. Começa com o aparecimento de pápulas pruriginosas que confluem até formar placas eritematosas, que aparecem primeiro no abdômen com exceção da área umbilical e geralmente parte das estrias e se espalham para as extremidades. O tratamento consiste no uso de emolientes e anti-histamínicos para o controle das lesões e o prurido. Conclusão. Ainda seja uma patologia benigna e autolimitada, é importante acertar o diagnóstico e iniciar o tratamento médico adequado, uma vez que sintomas como o prurido podem gerar arranhões que tendem a se infectar e comprometer o estado de saúde das pacientes. Cómo citar: Picón-Jaimes YA, Orozco-Chinome JE, Mejía-Antolínez LA, Garcés-Salamanca CT. Erupción polimorfa durante el puerperio inmediato. MedUNAB. 2019;22(1):64-70. doi:10.29375/01237047.3461

A Case of Post-Herpetic Nevoid Comedones

No abstract available.

Ictiose lamelar com apresentação na vida adulta: relato de caso / Ichthyosis lamellar with presentation in adult life: case report

Contexto: A ictiose lamelar é uma genodermatose rara, de herança autossômica recessiva. Pode ser causada por diferentes genes, principalmente mutação no gene TGM1 (transglutaminase 1) no cromossomo 14, e tem incidência de 1 caso em cada 200 mil nascidos vivos. A ictiose lamelar é causa de importante impacto na qualidade de vida. Relato da comunicação: Paciente do sexo feminino, 44 anos, procura atendimento médico para investigação de sintomas psiquiátricos, os quais foram avaliados. Foi afastado qualquer quadro psiquiátrico. Encaminhada à dermatologia, devido a evidente descamação lamelar disseminada, queratodermia palmoplantar, onicodistrofias e ectrópio bipalpebral. O exame clínico dermatológico e a avaliação histopatológica, evidenciaram características de ictiose lamelar, nunca tratada. Discussão: A ictiose lamelar é, na maioria das vezes, diagnosticada ao nascimento, com apresentação clínica muitas vezes sob a forma de bebê colódio. Este caso apresentou-se na vida adulta, com história desde o nascimento e, portanto, descartou-se a ictiose adquirida, relacionada a afecções nutricionais, metabólicas ou até paraneoplásicas. Conclusões: Este caso ilustra as manifestações da ictiose lamelar em paciente adulta em sua evolução natural, sem a interferência de tratamento.