Aerodynamic Simulation of Small Airway Resistance: A New Imaging Biomarker for Chronic Obstructive Pulmonary Disease.

Purpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD. Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted. Results: The RSA and RSA% were significantly different among the three groups (p<0.05) and related to FEV1/FVC (r = -0.70, p < 0.001; r = -0.67, p < 0.001), FEV1% predicted (r = -0.60, p = 0.002; r = -0.57, p = 0.004), MEF50% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001), MEF75% predicted (r = -0.71, p < 0.001; r = -0.60, p = 0.002) and MMEF 75/25% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001). Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.

WITHDRAWN: Coronary artery segmentation based on ACMA-Net and unscented Kalman filter algorithm.

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Chlorine-containing polyacetoxybriarane diterpenoids from the octocoral Junceella fragilis.

The chemical screening of an octocoral identifed as Junceella fragilis has led to the isolation of five chlorinated briarane-type diterpenoids, including three known metabolites, gemmacolide X (1), frajunolide I (2), and fragilide F (3), along with two new analogs, 12α-acetoxyfragilide F (4) and 12α-acetoxyjunceellin (5). Single-crystal X-ray diffraction analysis was carried out to determine the absolute configurations of 1 and 2, while the structures of new compounds 4 and 5 were ascertained with 2D NMR experiments. Briaranes 1 and 3-5 were active in enhancing alkaline phosphatase (ALP) activity.

Perineal Benign Symmetric Lipomatosis in a Female Patient: A Case Report.

BACKGROUND Benign symmetric lipomatosis (BSL), also known as Madelung's disease, is a rare disease generally characterized by fat deposits painlessly and symmetrically distributed in the body. In former studies, the incidence of BSL is highest in male patients and more frequent in the Mediterranean area. Asian females seem to be rarely affected. BSL often occurs in the neck or upper-back of patients, and is related to various metabolic disorders. Unusual clinical appearances may add difficulties in diagnosis. CASE REPORT In this report, we present a case of BSL in a 33-year-old woman's perineal region, with no clear BSL risk factors (sex, medical history, sites, and comorbidities), which increased the difficulties in diagnosis. The patient's quality of life was seriously affected by the continuous growth of fat tissue. Based on MRI and B-ultrasonic examinations, she underwent excision at our outpatient facility. Combined with the patient's clinical appearance, imaging results, and pathological tests, we could finally determine the diagnosis of BSL. After 18 months of follow-up, this patient recovered well with no recurrence. CONCLUSIONS Difficulties in diagnosis can seriously affect doctors' treatment approaches. BSL rarely occurs in the lower body, and our patient showed no clear risk factors. Therefore, imaging and pathological examinations can be essential tools for dermatological and plastic surgeons to diagnose and treat rare BSL.

Immunomodulatory and anti-angiogenesis effects of excavatolide B and its derivatives in alleviating atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and inflammatory responses. The marine natural product excavatolide B (EXCB), isolated from the Formosan Gorgonian coral Briareum stechei, exhibits anti-inflammatory and analgesic properties. To enhance solubility, EXCB is chemically modified into the derivatives EXCB-61 salt and EXCB-79. The study aims to investigate the therapeutic effects of these compounds on dinitrochlorbenzene (DNCB)-induced skin damage and to elucidate the underlying anti-inflammatory and anti-angiogenesis mechanism. In vitro, using lipopolysaccharide (LPS)-induced RAW 264.7 cells, all compounds at 10 µM significantly inhibited expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2), vascular endothelial growth factor (VEGF), and cytokines (interleukin (IL)-1ß, IL-6, and IL-17A). In vivo, topical application of these compounds on DNCB-induced AD mice alleviated skin symptoms, reduced serum levels of IgE, IL-4, IL-13, IL-17, and interferon-γ, and moderated histological phenomena such as hyperplasia, inflammatory cell infiltration, and angiogenesis. The three compounds restored the expression of skin barrier-related proteins (loricrin, filaggrin, and claudin-1) and reduced the expression of angiogenesis-related proteins (VEGF and platelet endothelial cell adhesion molecule-CD31) in the tissues. This is the first study to indicate that EXCB, EXCB-61 salt, and EXCB-79 can treat AD disease by reducing inflammation and angiogenesis. Hence, they may be considered potential candidates for the development of new drugs for AD.

Comprehensive aesthetic corrections of gynecomastia using the reproducible safe and minimally invasive surgical strategy.

BACKGROUND: Minimally invasive access and fast recovery are trends of gynecomastia surgery. We placed great importance on liposuction and modified original pull-through technique. The purpose of this study was to present a refined surgical strategy for gynecomastia in grade I and II. METHODS: The refined strategy embraced enhanced liposuction to remove the intraglandular fat sufficiently, followed by open resection of gland using the pull-through and bottom-up technique with adjuvant liposuction in the end. Surgical data were recorded and satisfactory questionnaires with 5-point scales were administered during follow-up. RESULTS: Between January 2017 and May 2022, 165 patients underwent enhanced liposuction combined with the pull-through and bottom-up technique for gland excision. Age ranged from 12 to 56 years. The median length of surgery was 100 min. A median of 300 ml of fat was aspirated and a median of 20.8 g of gland was excised. Seventy-seven patients (46.7%) responded the questionnaires at least 6 months postoperatively, and the average overall satisfaction was 4.68 ± 0.52 points. Thirteen sides of breasts developed complications with a rate of 4.0%. CONCLUSION: Enhanced liposuction combined with pull-through and bottom-up technique proved effective to treat grade I and II gynecomastia with minimal scarring and high satisfaction. The refined strategy was simple and safe, and would obtain optimal outcomes even for inexperienced surgeons.

The biomarkers associated with epithelial-mesenchymal transition in human keloids.

INTRODUCTION: A keloid is a type of benign fibrotic disease with similar features to malignancies, including anti-apoptosis, over-proliferation, and invasion. Epithelial-mesenchymal transition (EMT) is a crucial mechanism that regulates the metastatic behavior of tumors. Thus, identifying EMT biomarkers is paramount in comprehensively understanding keloid pathogenesis. METHODS: To identify the differentially expressed genes (DEGs) GSE92566 dataset, with 3 normal skin and 4 keloid tissues, was downloaded from GEO databases to identify the differentially expressed genes (DEGs). Further, EMT-related genes were downloaded from dbEMT 2.0 databases and intersected with GSE92566 DEGs to identify EMT-related-DEGs (ERDEGs). Subsequently, the ERDEGs were used for GO, KEGG, gene set enrichment analysis (GSEA), protein-protein interaction (PPI), and miRNAs-mRNAs network analysis. To predict small molecules for EMT inhibition, the ERDEGs were imported to cMAP databases, whereas hub genes were imported to DGidb databases. Finally, we carried out qRT-PCR and in vitro experiments to validate our findings. RESULTS: A total of 122 ERDEGs were identified, including 59 upregulated and 63 down-regulated genes. Moreover, enrichment analysis revealed that focal adhesion, AMPK signal pathway, Wnt signal pathway, and EMT biological process were significantly enriched. STRING databases and Cytoscape software were used to construct the PPI network and EMT-related hub genes. Further, 3 modules were explored from the PPI network using the Molecular Complex Detection (MCODE) plugin. In the Cytohubba plugin, 10 hub genes were explored, including FN1, EGF, SOX9, CDH2, PROM1, EPCAM, KRT19, ITGB1, CD24, and KRT18. These genes were then enriched for the focal adhesion pathway. We constructed a microRNA (miRNA)-mRNA network, which predicted hsa-miR-155-5p (8 edges), hsa-miR-124-3p (7 edges), hsa-miR-145-5p (5 edges), hsa-miR-20a-5p (5 edges) and hsa-let-7b-5p (4 edges) as the most connected miRNAs regulating EMT. Based on the ERDEGs and 10 hub genes mentioned above, ribavirin demonstrated high drug-targeting relevance. Subsequently, qRT-PCR confirmed that the expression of FN1, ITGB1, CDH2, and EPCAM corroborated with previous findings. qRT-PCR also showed that the expression levels of hsa-miR-124-3p and hsa-miR-145-5p were significantly lower in keloids and hsa-miR-155-5p was upregulated in keloids. Finally, by treating human keloid fibroblasts (HKFs) with ribavirin in vitro, we confirmed that ribavirin could inhibit HKFs proliferation and EMT. CONCLUSION: In summary, this work provides novel EMT biomarkers in keloids and predicts new small target molecules for keloid therapy. Our findings improve the understanding of keloid pathogenesis, providing new treatment options.

Joint effect of RRP9 and DDX21 on development of colorectal cancer and keloid.

BACKGROUND: Colorectal cancer (CRC) is a common malignancy in the gastrointestinal tract. Keloid refers to abnormal scar tissue that forms on the skin or mucous membrane. The relationship between RRP9 and DDX21 and the two diseases is unclear. METHODS: Download the colorectal cancer dataset GSE134834, GSE206800, GSE209892 and keloid dataset GSE44270 from the GEO database. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. The construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, gene set enrichment analysis (GSEA). Gene expression heat map was drawn. The comparative toxicogenomics database (CTD) analysis was performed to find diseases most related to core genes. TargetScan screened miRNAs that regulated central DEGs. We conducted experimental validation using Western blotting and Polymerase Chain Reaction (PCR). RESULTS: In the colorectal cancer dataset and the scar tissue dataset, we identified 1380 DEGs and 1000 DEGs, respectively. The enrichment pattern for scar tissue was similar to that of colorectal cancer. We identified two core genes, RRP9 and DDX21. CTD analysis indicated that RRP9 and DDX21 are associated with proliferation, scar tissue, colorectal tumors, scleroderma, and inflammation. We found that the core genes (RRP9 and DDX21) were highly expressed in colorectal cancer and scar tissue samples, while their expression was lower in normal samples. This was further validated through Western blotting (WB) and Polymerase Chain Reaction (PCR). CONCLUSIONS: The higher the expression of RRP9 and DDX21 in colorectal cancer and keloid, the worse the prognosis.

Developing a human iPSC-derived three-dimensional myelin spheroid platform for modeling myelin diseases.

Myelin defects cause a collection of myelin disorders in the brain. The lack of human models has limited us from better understanding pathological mechanisms of myelin diseases. While human induced pluripotent stem cell (hiPSC)-derived spheroids or organoids have been used to study brain development and disorders, it has been difficult to recapitulate mature myelination in these structures. Here, we have developed a method to generate three-dimensional (3D) myelin spheroids from hiPSCs in a robust and reproducible manner. Using this method, we generated myelin spheroids from patient iPSCs to model Canavan disease (CD), a demyelinating disorder. By using CD patient iPSC-derived myelin spheroids treated with N-acetyl-aspartate (NAA), we were able to recapitulate key pathological features of the disease and show that high-level NAA is sufficient to induce toxicity on myelin sheaths. Our study has established a 3D human cellular platform to model human myelin diseases for mechanistic studies and drug discovery.

The Apolipoprotein E neutralizing antibody inhibits SARS-CoV-2 infection by blocking cellular entry of lipoviral particles.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent for coronavirus disease 2019 (COVID-19). Although vaccines have helped to prevent uncontrolled viral spreading, our understanding of the fundamental biology of SARS-CoV-2 infection remains insufficient, which hinders effective therapeutic development. Here, we found that Apolipoprotein E (ApoE), a lipid binding protein, is hijacked by SARS-CoV-2 for infection. Preincubation of SARS-CoV-2 with a neutralizing antibody specific to ApoE led to inhibition of SARS-CoV-2 infection. The ApoE neutralizing antibody efficiently blocked SARS-CoV-2 infection of human iPSC-derived astrocytes and air-liquid interface organoid models in addition to human ACE2-expressing HEK293T cells and Calu-3 lung cells. ApoE mediates SARS-CoV-2 entry through binding to its cellular receptors such as the low density lipoprotein receptor (LDLR). LDLR knockout or ApoE mutations at the receptor binding domain or an ApoE mimetic peptide reduced SARS-CoV-2 infection. Furthermore, we detected strong membrane LDLR expression on SARS-CoV-2 Spike-positive cells in human lung tissues, whereas no or low ACE2 expression was detected. This study provides a new paradigm for SARS-CoV-2 cellular entry through binding of ApoE on the lipoviral particles to host cell receptor(s). Moreover, this study suggests that ApoE neutralizing antibodies are promising antiviral therapies for COVID-19 by blocking entry of both parental virus and variants of concern.

Marine diterpenoid targets STING palmitoylation in mammalian cells.

Natural products are important sources of therapeutic agents and useful drug discovery tools. The fused macrocycles and multiple stereocenters of briarane-type diterpenoids pose a major challenge to total synthesis and efforts to characterize their biological activities. Harnessing a scalable source of excavatolide B (excB) from cultured soft coral Briareum stechei, we generated analogs by late-stage diversification and performed structure-activity analysis, which was critical for the development of functional excB probes. We further used these probes in a chemoproteomic strategy to identify Stimulator of Interferon Genes (STING) as a direct target of excB in mammalian cells. We showed that the epoxylactone warhead of excB is required to covalently engage STING at its membrane-proximal Cys91, inhibiting STING palmitoylation and signaling. This study reveals a possible mechanism-of-action of excB, and expands the repertoire of covalent STING inhibitors.

Induction of Immune Responses and Phosphatidylserine Exposure by TLR9 Activation Results in a Cooperative Antitumor Effect with a Phosphatidylserine-targeting Prodrug.

Head and neck cancer is a major cancer type, with high motility rates that reduce the quality of life of patients. Herein, we investigated the effectiveness and mechanism of a combination therapy involving TLR9 activator (CpG-2722) and phosphatidylserine (PS)-targeting prodrug of SN38 (BPRDP056) in a syngeneic orthotopic head and neck cancer animal model. The results showed a cooperative antitumor effect of CpG-2722 and BPRDP056 owing to their distinct and complementary antitumor functions. CpG-2722 induced antitumor immune responses, including dendritic cell maturation, cytokine production, and immune cell accumulation in tumors, whereas BPRDP056 directly exerted cytotoxicity toward cancer cells. We also discovered a novel function and mechanism of TLR9 activation, which increased PS exposure on cancer cells, thereby attracting more BPRDP056 to the tumor site for cancer cell killing. Killed cells expose more PS in tumor for BPRDP056 targeting. Tumor antigens released from the dead cells were taken up by antigen-presenting cells, which enhanced the CpG-272-promoted T cell-mediated tumor-killing effect. These form a positive feed-forward antitumor effect between the actions of CpG-2722 and BPRDP056. Thus, the study findings suggest a novel strategy of utilizing the PS-inducing function of TLR9 agonists to develop combinational cancer treatments using PS-targeting drugs.

Gluteal Fold: Cadaveric Dissection of the Superficial Fascial System in the Buttock and Anatomy-based Gluteal Liposculpture.

BACKGROUND: The anatomy and formation mechanism of the gluteal fold (GF) remain unclear. Given that understanding the anatomy of the superficial fascial system (SFS) may facilitate the improvement of liposuction techniques, this study aimed to clarify and define the anatomic components of the GF. METHODS: A total of 20 fresh female buttocks and thighs were sagittally dissected to observe the changes of the SFS along the GF, and were horizontally dissected to observe the SFS on the upper, middle, and lower levels of the buttock. RESULTS: Through these dissections, two patterns of SFS in the GF region were identified: retinaculum cutis (RC)-dominant SFS, named the fascial condensation zone, features extremely dense and tough RC, originating from the bony structures, such as the ischium, and radially anchored by the dermis. The fat-dominant SFS features a classical double-layered SFS structure. The RC-dominant SFS is mainly distributed at the medial GF, thus forming the depressed fold. It gradually disappears along the GF and the SFS becomes fat-dominant, making the fold increasingly less visible. At the lateral buttock, the SFS of the buttock and thigh reach an identical status in terms of morphological features, showing a smooth curve between the buttock and the thigh instead of a fold. Hence, based on these findings, different liposuction methods were formulated to manage GF contouring. CONCLUSIONS: The SFS of GF region shows a regional variation pattern. Topographic anatomy of the SFS in the GF region helps us understand GF contour deformities and provide an anatomic basis for surgical correction.

2-Methoxyestradiol inhibits the proliferation level in keloid fibroblasts through p38 in the MAPK/Erk signaling pathway.

BACKGROUND: The MAPK/Erk signaling pathway is a classic pathway in cell proliferation. Our former study showed that keloid tissue revealed a higher proliferation level than physiological scars and normal skin. As a natural metabolite of estradiol, 2-methoxyestradiol (2ME2) showed an inhibition proliferation effect on tumor cells. AIM: In this study, the treatment effect of 2ME2 and its potential mechanisms are explored. METHODS: Six keloid patients and six non-keloid patients were randomly selected from the Department of Plastic Surgery at our hospital during June 2021 to December 2021. Six groups were established: normal skin fibroblasts (N); keloid fibroblasts (K); keloid fibroblasts treated with 2ME2 (K + 2ME2); keloid fibroblasts treated with dimethyl sulfoxide (DMSO) (K + DMSO); keloid fibroblasts treated with doramapimod (K + IN); keloid fibroblasts treated with doramapimod (p38 inhibitor) and 2ME2 (K + IN+2ME2). The fibroblast activity and key factor expression of the MAPK/Erk signaling pathway were measured. RESULTS: In the results, 2ME2 significantly inhibited keloid fibroblast activity and key factor expression (except STAT1). CONCLUSION: The proliferation levels were reduced by both the p38 inhibitor and 2ME2, indicating 2ME2 may achieve an antiproliferation effect by targeting p38 in keloid fibroblasts.

Standardized Photography of Female Genitalia and Anatomical Evaluations.

BACKGROUND: Standardized photographic recording and anatomic evaluation are crucial to refined and comprehensive preoperative design and enhanced aesthetic effect of female genital cosmetic surgery. OBJECTIVES: The authors aim to propose a standard photographic scheme and physical examination form for the anatomical assessment of patients undergoing female genital surgery. METHODS: The scheme containing 2 positions (standing and lithotomy positions) and 11 views (1 frontal and 2 oblique views from standing position; 6 frontal views with labia minora open and closed, pulled to the opposite side, clitoral hood pushed up, posterior fourchette stretched; 2 oblique views from lithotomy position) (2P11V) is applied to record pre- and postoperative appearance of the vulva. The evaluation form is utilized to record characteristics of different anatomical subunits during photography. RESULTS: Two hundred forty-five patients who underwent female genital surgery were enrolled in the research from October 2018 to October 2022. All the patients received preoperative and postoperative 2P11V photography with about 5-minutes' shooting time. Various anatomical variations containing hypertrophy and prolapse of mons pubis, redundant types of labia minora and clitoral hood, incremental exposure of clitoral glans, hypo- to hypertrophy of labia majora, disappearance of interlabial groove, hypertrophy of posterior fourchette, and relation of subunits were accurately documented. CONCLUSIONS: 2P11V photographic scheme displays the isolated features of each organ and proportion relation among different parts of vulva. The standard photographic record and physical examination form offer detailed anatomical structure to surgeons and facilitate surgeons to carry out an accurate surgical design, which deserve to be promoted and applied.

Labiaplasty in Adolescents: Indications and Treatment Protocol.

BACKGROUND: Adolescents constitute a unique group of labia minora hypertrophy patients, but the necessity and benefits of labiaplasty for adolescents remain controversial. OBJECTIVES: The purpose of this study was to summarize the surgical indications, the details of the treatment procedure, postoperative complications, and therapeutic outcomes of labiaplasty in the adolescent population. METHODS: A retrospective chart review was performed of adolescent patients aged <18 years old who underwent labiaplasty between January 2016 and May 2022. Patient characteristics, surgical method, concomitant procedures, procedure side, operative time, complications, and follow-up data were recorded. RESULTS: A total of 12 patients aged <18 years were included in this study. All procedures were performed for functional reasons. The mean [standard deviation] operative time was 61.75 [20.77] minutes (range, 38-114 minutes). Unilateral labia minora hematoma within 24 hours occurred in 2 of the 12 patients (16.7%) and surgical evacuations were performed immediately. All patients were followed up electronically at 42.33 [16.88] months (range, 14-67 months). Notably, 83.33% (10/12) of patients reported being very satisfied, and 16.67% (2/12) of patients were satisfied. There was no patient dissatisfaction. Preoperative discomfort was completely resolved in 9 patients (75.00%) and significantly improved in 3 patients (25.00%). Furthermore, no patients indicated that symptoms were not improved or made worse. CONCLUSIONS: In the adolescent population, severe hypertrophy of the labia minora and the clitoral hood will cause discomfort, affecting the quality of life and mental health. Therefore, labiaplasty is a safe and effective procedure in adolescents to improve genital appearance and quality of life.

A high-fidelity geometric multiscale hemodynamic model for predicting myocardial ischemia.

BACKGROUND AND OBJECTIVES: Coronary computed tomography angiography (CCTA) derived fractional flow reserve (CT-FFR) requires a maximal hyperemic state to be modeled by assuming the total coronary resistance decreased to a constant 0.24 of that under the resting state. However, this assumption neglects the vasodilator capacity of individual patients. Herein, we proposed a high-fidelity geometric multiscale model (HFMM) to characterize coronary pressure and flow under the resting state, seeking to better predict myocardial ischemia by using CCTA-derived instantaneous wave-free ratio (CT-iFR). METHODS: Fifty-seven patients (62 lesions) who had undergone CCTA and were then referred to invasive FFR were prospectively enrolled. The coronary microcirculation resistance hemodynamic model (RHM) under the resting condition was established on a patient-specific basis. Coupled with a closed-loop geometric multiscale model (CGM) of their individual coronary circulations, the HFMM model was established to non-invasively derive the CT-iFR from CCTA images. RESULTS: With the invasive FFR being the reference standard, accuracy of the obtained CT-iFR in identifying myocardial ischemia was greater than those of the CCTA and non-invasively derived CT-FFR (90.32% vs. 79.03% vs. 84.3%). The overall computational time of CT-iFR was 61 ± 6 min, faster than that of the CT-FFR (8 h). The sensitivity, specificity, positive predictive value, and negative predictive value of the CT-iFR in discriminating an invasive FFR > 0.8 were 78% (95% CI: 40-97%), 92% (95% CI: 82-98%), 64% (95% CI: 39-83%), and 96% (95% CI:88-99%), respectively. CONCLUSIONS: A high-fidelity geometric multiscale hemodynamic model was developed for rapid and accurate estimation of CT-iFR. Compared with CT-FFR, CT-iFR is of less computational cost and enables assessment of tandem lesions.

Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition.

BACKGROUND: Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. H2 has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how H2 functions in wound healing remains unknown, especially for the link between H2 and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. METHODS: Here, we established a cutaneous aseptic wound model and applied a high concentration of H2 (66% H2) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. RESULTS: We revealed that a high concentration of H2 (66% H2) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on O2 or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the H2 group. ECM components early (3 days post-wounding) deposition were found in the H2 group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. H2 accelerated early autologous EpSCs proliferation (1-2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. CONCLUSION: We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between H2 and ECM deposition and EpSCs activation. These H2-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life.

Risk factors associated with keloid infections: A five-year retrospective study.

Keloid infections reduce patient-reported quality of life greatly. Characteristics and risk factors of keloid infections have not been thoroughly studied. So, a retrospective cohort study was conducted focusing on the potential risk factors, microbiologic cultures and histological findings. Keloid patients consulting for surgical interventions were included in this study. Data were collected from their electronic medical records. 564 patients were recruited with the keloid infection rate being 22.4%. For adult patients, age above 40 years (OR, 2.84; P = .000), disease duration of 12 years or more (OR, 3.03; P = .000), the number of keloids over 3 (OR, 1.59; P = .050) and the presence of family history (OR, 1.91; P = .027) were significantly associated with keloid infections. Suppurative keloids were located mostly in thorax (61.79%). For the under-age subgroup(n = 25), family history was frequently seen in patients with infections. Microbiologic cultures revealed a mixed spectrum of bacteria including Staphylococcus (25%), Actinomyces (30%) and Prevotella (10%). The rate of epidermoid cysts was 19.7% in histological examination. Age > 40 years, disease duration ≥12 years, the number of keloids >3 and the presence of family history are risk factors for keloid infections.

Role of HIF-1α in pathogenic mechanisms of keloids.

BACKGROUDS AND OBJECTIVE: Keloids are defined as overrepairing products that develop after skin lesions. Keloids are characterized by the proliferation of fibroblasts and the overaccumulation of extracellular matrix components (mainly collagen), leading to a locally hypoxic microenvironment. Hence, this article was aimed to review hypoxia in pathogenesis of keloids. METHODS: We reviewed and summarized the relevant published studies. RESULTS: Hypoxia results in the accumulation of hypoxia-inducible factor 1α (HIF-1α) in keloids, contributing to overactivation of the fibrotic signaling pathway, epithelial-mesenchymal transition, and changes in metabolism, eventually leading to aggravated fibrosis, infiltrative growth, and radiotherapy resistance. CONCLUSION: It is, therefore, essential to understand the role of HIF-1α in the pathogenic mechanisms of keloids in order to develop new therapeutic approaches.