Itraconazole Oral Solution for Infantile Complicated Hemangioma with Double Lesions on the Skin and One Inside the Liver.

An infantile hemangioma is a congenital benign tumor formed by the proliferation of vascular cells during the embryonic stage. It is more common in the skin but can also occur in the mucous membranes, liver, brain and muscle. Hepatic hemangioma appears to be a benign tumor; however, it may lead to poor outcomes because of severe complications, such as high-output cardiac failure. The main treatment of hepatic hemangioma in infants is oral drugs, such as propranolol and glucocorticoids, but the clinical response is not always satisfactory. We describe a rare case of a 2-month-old boy who presented with infantile cutaneous and hepatic hemangiomas. By using dermoscopy and observations of the abdominal color Doppler ultrasound, after 9 months of oral treatment with itraconazole solution, the infantile cutaneous hemangioma complicated with hepatic hemangioma was eventually cured. There was no liver or kidney function damage during the whole treatment period. Itraconazole oral solution for the treatment of infantile cutaneous hemangioma complicated with hepatic hemangioma showed good efficacy, compliance, and safety in this case.

Cage-modified hypocrellin against multidrug-resistant Candida spp. with unprecedented activity in light-triggered combinational photodynamic therapy.

Infections caused by multidrug-resistant fungi pose a devastating threat to human health worldwide, making new antifungal strategies urgently desired. Antimicrobial photodynamic therapy (aPDT) has gained increasing attention due to its potential in fighting against fungal infection. However, the preparation of highly efficient and water-soluble photosensitizers (PSs) for this purpose remains a challenge. Herein, we present a new strategy to prepare powerful PSs for efficient aPDT by introducing a porous cage compound, which could facilitate the transportation of O2 and reactive oxygen species (ROS). Specifically, the natural PS hypocrellin A (HA) was attached to a novel organic cage compound (covalent organic polyhedra 1 tied, COP1T) with polyethylene glycol (PEG) chains to improve its water solubility. It was found that the resulting COP1T-HA exhibited in vitro antifungal efficiency several folds higher compared to the free HA in fighting against four types of multidrug-resistant fungal planktonic cells and biofilms, including the "super fungus" Candida auris. Interestingly, the red-shift of COP1T-HA adsorption led to the realization of phototheranostic aPDT for cage-modified HA or derivatives. Additionally, COP1T-HA exhibited good biocompatibility, excellent disinfection capacity and wound healing efficiency without obvious toxic effects in vivo of rat model. With further development and optimization, COP1T-HA has great potential to become a new class of antifungal agent to fight against drug-resistant pathogens.

Colorectal liver metastasis: molecular mechanism and interventional therapy.

Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors with a high morbidity additionally, CRC patients may develop liver metastasis, which is the major cause of death. Despite significant advances in diagnostic and therapeutic techniques, the survival rate of colorectal liver metastasis (CRLM) patients remains very low. CRLM, as a complex cascade reaction process involving multiple factors and procedures, has complex and diverse molecular mechanisms. In this review, we summarize the mechanisms/pathophysiology, diagnosis, treatment of CRLM. We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM, further improving the prognosis of CRLM patients.

A rare case of extensive gingival lymphatic malformation.

Lymphatic malformation is a benign lesion, seldom affecting the gingiva. Gingival lesions are characterized by pebbly hyperplasia, occasional pain, and bleeding. The treatment for large and exceptional areas of involvement may face difficulties. Herein we report a rare case of gingival lymphatic malformation in a 10-year-old girl.

Nocardia huaxiensis sp. nov., an actinomycete isolated from human skin.

A novel actinomycete, designated as strain WCH-YHL-001T, was isolated from skin biopsy specimens of a patient at West China Hospital, Chengdu, Sichuan Province, PR China. The cells were Gram-positive, aerobic, heterotrophic and non-motile. They formed an extensive substrate with short aerial mycelia, whose branches fragmented into rod-shaped elements. Growth occurred at 10-40 °C, pH 5.0-12.0 and with NaCl concentrations of 0-4.0 % (w/v). The major cellular fatty acids of strain WCH-YHL-001T were C16 : 0, C18 : 1 ω9c, C18 : 0 10-methyl and summed feature 3. The predominant respiratory quinone was MK-8 (H4ω-cycl). The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol mannoside, unknown phospholipids and unidentified glycolipids. The diagnostic diamino acid of peptidoglycan was meso-diaminopimelic acid. The whole-cell sugar pattern consisted of arabinose and glucose. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain WCH-YHL-001T belonged to the genus Nocardia. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strain WCH-YHL-001T and type strains of Nocardia species were lower than the cut-offs (≥95-96 % for ANI and ≥70 % for isDDH) required to define a bacterial species. The genomic DNA G+C content was 67.8 mol%. Phylogenetic, physiological and chemotaxonomic data suggested that strain WCH-YHL-001T represented a novel species of the genus Nocardia, for which the name Nocardia huaxiensis sp. nov. is proposed, with the type strain WCH-YHL-001T (=GDMCC 4.181T=JCM 34475 T=NBRC 114973T).

Itraconazole Oral Solution for a Case of Infantile Hemangioma: Monitoring the Efficacy by Dermoscopy and MRI.

Infantile hemangioma is a common and challenging benign vascular tumor. Although involution is spontaneous, approximately 10% of infantile hemangioma of large size or in specific locations may cause ulceration, severe cosmetic and functional problems that may require intervention. Treatment options include oral propranolol, topical timolol, and oral corticosteroids. However, the clinical response is not always satisfactory. We report the case of a 4-month-old boy who presented with an irregular erythematous plaque on his left shoulder 3 days after birth. Infantile hemangioma was diagnosed. Topical application of 0.5 ml of 0.5% timolol maleate eye drops for half an hour each time three times a day was initiated. After nearly 3 months of follow-up, the size of the lesion gradually increased. Finally, after 115 days of treatment with itraconazole oral solution (the total dose was about 4025 mg), the refractory infantile hemangioma was successfully treated. Hepatic and renal function remained normal with only mild diarrhea during the course of oral medication. Treatment compliance of oral itraconazole in infants has been reported to be good. Dermoscopy and magnetic resonance imaging (MRI) played a crucial role in in vivo observation of the hemangioma changes with vascular regression during the treatment process.

Clinical parameters associated with severity of nail psoriasis and therapeutic efficacy.

BACKGROUND: Nail involvement is common in psoriasis patients, however, there are few detailed studies of clinical parameters related to disease severity and therapeutic efficacy. OBJECTIVES: Our retrospective study aimed to describe the prevalence and clinical characteristics in nail psoriasis patients and determine possible associations between multiple clinical parameters and disease severity or therapeutic efficacy. MATERIALS AND METHODS: A total of 89 nail psoriasis patients were included and investigated using dermoscopy. The Nail Psoriasis Severity Index (NAPSI) and the Nijmegen-Nail Psoriasis Activity Index tool (N-NAIL) were used to measure the severity and improvement of nail psoriasis. Severity and efficacy-related parameters were also analysed. RESULTS: Subungual hyperkeratosis (94.4%) was the most commonly observed nail feature. Coexistence of pitting and leukonychia, transverse grooves and thickening were more commonly observed in juveniles than adults. Patients with more severe nail psoriasis were more likely to have more nails affected and develop discolouration. The efficacy of treatment after fixed intervals of treatment was analysed. Most clinical parameters were not related to therapeutic efficacy, including disease duration, age at onset and number of nail signs. However, after six months of treatment, the presence of transverse grooves was shown to be associated with better efficacy. Based on comparison of NAPSI and N-NAIL scores relative to the first visit, the presence of transverse grooves, longitudinal ridges or discolouration were associated with better efficacy. CONCLUSION: Clinicians should be aware of the clinical parameters related to severity and the use of therapeutic efficacy in choosing individualized treatment and predicting prognosis.

Successful Treatment of Refractory Candidal Granuloma by Itraconazole and Terbinafine in Combination with Hyperthermia and Cryotherapy.

Candidal granuloma is a rare and refractory disease in clinical practice, usually reported in immunocompromised patients. We report a 57-year-old man who presented with candidal granuloma caused by Candida tropicalis. The diagnosis was confirmed according to histopathology and molecular identification. Prolonged duration of initial antifungal therapy did not obtain satisfactory improvement. Finally, the refractory disease was successfully treated by itraconazole and terbinafine in combination with hyperthermia and cryotherapy. The "blackish-red dot" dermoscopic sign of the verrucous granuloma gradually resolved during the treatment.

A powerful combination of copper-cysteamine nanoparticles with potassium iodide for bacterial destruction.

Herein, for the first time, we demonstrate that the combination of copper-cysteamine (Cu-Cy) nanoparticles (NPs) and potassium iodide (KI) can significantly inactivate both Gram-positive MRSA and Gram-negative E. coli. To uncover the mystery of the killing, the interaction of KI with Cu-Cy NPs was investigated systematically and the products from their interaction were identified. No copper ions were released after adding KI to Cu-Cy NPs in cell-free medium and, therefore, it is reasonable to conclude that the Fenton reaction induced by copper ions is not responsible for the bacterial killing. Based on the observations, we propose that the major killing mechanism involves the generation of toxic species, such as hydrogen peroxide, triiodide ions, iodide ions, singlet oxygen, and iodine molecules. Overall, the powerful combination of Cu-Cy NPs and KI has good potential as an independent treatment or a complementary antibiotic treatment to infectious diseases.

Biological and genomic analyses of a clinical isolate of Yarrowia galli from China.

Infections caused by emerging fungal pathogens represent a new threat to human health. The yeast Yarrowia (Candida) galli was first described from chicken breast and liver in 2004 and has occasionally been isolated in clinical settings. In this study, we present the first report of a Y. galli isolate from a face granuloma of a woman. Y. galli is unable to grow at human physiological temperature (37 °C). Phenotypic analysis demonstrates that Y. galli can exist as several morphological types, namely fluffy, sticky, tight, and yeast forms, based on their cellular and colony appearances. Interestingly, Y. galli is able to undergo switching among different morphologies. These morphological changes are similar to the switching systems in pathogenic Candida species such as Candida albicans and Candida tropicalis. We further sequenced the genome of the Y. galli isolate. A comparative analysis with pathogenic yeast species indicated that a set of lipid metabolism genes were enriched in Y. galli. Domain enrichment analysis demonstrated that, similar to Candida clade species, the genome of Y. galli maintained several gene families required for virulence. Our biological and genomic analyses provide new insights into the understanding of the biology of Y. galli as either an environmental isolate or a potential human pathogen.

Itraconazole Induces Regression of Infantile Hemangioma via Downregulation of the Platelet-Derived Growth Factor-D/PI3K/Akt/mTOR Pathway.

Infantile hemangioma is the most common benign vascular tumor of infancy. We have previously reported that itraconazole, a common antifungal agent, can clinically improve or cure infantile hemangioma; however, the underlying molecular mechanisms are still unclear. Here, we show that itraconazole treatment significantly inhibits proliferation and promotes apoptosis of the endothelial cells of mouse hemangioma cell line and infantile primary hemangioma endothelial cell. Itraconazole also remarkably reduced angiogenesis of hemangioma endothelial cell in vitro. We further performed transcriptome profiling via mRNA microarrays in hemangioma endothelial cell upon itraconazole treatment, and identified cytokine-cytokine receptor interaction as the top significantly enriched pathway. Importantly, itraconazole significantly reduced platelet-derived growth factor-D level, resulting in suppression of platelet-derived growth factor-ß activation and inhibition of its downstream effectors, such as PI3K, Akt, 4E-BP1, and p70S6K, which are important for cellular growth and survival of infantile hemangioma. In conclusion, our results suggest that platelet-derived growth factor-D is a target of itraconazole in infantile hemangioma.

Phenformin Enhances the Efficacy of ERK Inhibition in NF1-Mutant Melanoma.

Inactivation of the tumor suppressor neurofibromin 1 (NF1) presents a newly characterized melanoma subtype, for which currently no targeted therapies are clinically available. Preclinical studies suggest that extracellular signal-regulated kinase (ERK) inhibitors are likely to provide benefit, albeit with limited efficacy as a single agent; therefore, there is a need for rationally designed combination therapies. Here, we evaluate the combination of the ERK inhibitor SCH772984 and the biguanide phenformin. A combination of both compounds showed potent synergy in cell viability assays and cooperatively induced apoptosis. Treatment with both drugs was required to fully suppress mechanistic target of rapamycin signaling, a known effector of NF1 loss. Mechanistically, SCH772984 increased the oxygen consumption rate, indicating that these cells relied more on oxidative phosphorylation upon treatment. Consistently, SCH772984 increased expression of the mitochondrial transcriptional coactivator peroxisome proliferator-activated receptor gamma, coactivator 1-α. In contrast, cotreatment with phenformin, an inhibitor of complex I of the respiratory chain, decreased the oxygen consumption rate. SCH772984 also promoted the expansion of the H3K4 demethylase KDM5B (also known as JARID1B)-positive subpopulation of melanoma cells, which are slow-cycling and treatment-resistant. Importantly, phenformin suppressed this KDM5B-positive population, which reduced the emergence of SCH772984-resistant clones in long-term cultures. Our results warrant the clinical investigation of this combination therapy in patients with NF1 mutant melanoma.

Linear atrophoderma of Moulin: a disease related to immunity or a kind of connective tissue disease?

We describe a 28-year-old man with linear atrophoderma of Moulin (LAM), whose serum immunological markers were abnormal (including antinuclear antibody, ribonucleoprotein, immunoglobulin M and anti-SM antibody). In addition, however, a histological analysis identified unexpected connective tissue disease changes in this patient. We speculate that the pathogenesis of LAM is associated with immunity or that LAM itself is a kind of connective tissue disease.