Ionizable drug delivery systems for efficient and selective gene therapy.

Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function. However, a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells. To be excited, the development of ionizable drug delivery systems (IDDSs) has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019 (COVID-19) in 2021. Compared with conventional cationic gene vectors, IDDSs can decrease the toxicity of carriers to cell membranes, and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures. Despite the progress, there remain necessary requirements for designing more efficient IDDSs for precise gene therapy. Herein, we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms. The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of pDNA and four kinds of RNA. In particular, organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity. We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future, and indicate ideas for developing next generation gene vectors.

Cutaneous sarcoidosis mimicking pigmented purpuric dermatosis.

Sarcoidosis is a systemic inflammatory disorder characterized by the formation of non-caseating granulomas. Cutaneous involvement of sarcoidosis is common and has a wide variety of clinical presentations. Herein, we present a case of cutaneous sarcoidosis mimicking pigmented purpuric dermatosis (PPD) in a 26-year-old female treated with topical tofacitinib cream and a literature review of all other reported cases of cutaneous sarcoidosis with PPD-like features.

Fatal melanoma with a novel MYO5A-BRAF fusion and small associated conventional nevus: A case report and review of literature.

Kinase fusions play an important role in the pathogenesis of Spitz neoplasms and occasionally non-Spitz neoplasms. We report a case of a 19-year-old woman with a growing nodule on the scalp, morphologically consistent with a diagnosis of melanoma with epithelioid features arising in association with small nevus. This tumor aggressively metastasized and failed to respond to immunotherapy. Next-generation sequencing of a metastatic focus revealed an MYO5A-BRAF kinase fusion with a low mutational burden and fluorescence in situ hybridization (FISH) of the primary melanoma showed similar results. FISH testing of the associated nevus failed because of technical reasons. MYO5A has rarely been reported as the fusion partner with BRAF-rearranged melanocytic tumors. Moreover, this case raises speculations and contributes to the growing literature on the pathogenesis, nomenclature, and tumorigenic pathways in kinase-fusion melanomas. The patient succumbed to disease, which is in concordance with some literature suggesting aggressive behavior of BRAF fusion melanomas with TERT promoter mutations.

Lichen planus of the eyelids: a case report and review of the literature.

Lichen planus (LP) of the eyelid is an under-reportedmanifestation of a common inflammatory condition.To the best of our knowledge fewer than 20 cases ofeyelid LP have been described in the English literature.We report a case of a 29-year-old woman whopresented with 3-month history of bilateral eyelidpruritic violaceous papules and similar lesions on herchest and lower extremity. Histology examinationrevealed characteristic findings and a diagnosisof LP was established. This report further reviewsthe previously reported 18 cases and discussesmanagement strategies.

Precursor-B-cell-ALL leukemia cutis resembling lipomas: an atypical presentation of a rare entity and a review of the literature.

Leukemia cutis (LC) is an extramedullary manifestationof leukemia owing to cutaneous infiltration ofneoplastic cells resulting in characteristic firm,erythematous nodules. Most cases of LC occur inpatients with acute myelogenous leukemia andchronic myelogenous leukemia. However in rarecases, LC has presented in patients with acutelymphoblastic leukemia (ALL). In these rare ALLassociatedcases, only 10 cases of precursor-B-ALL(pre-B-ALL) have been described in the literature.We report a case of a 22-year-old man with relapsingpre-B-ALL who presented with a 4-day history ofmultiple asymptomatic, soft, dome-shaped, lipomalikemounds on his scalp and chin, which exhibitedcutaneous involvement by leukemic cells. To date, thisis the first case of pre-B-ALL associated leukemia cutispresenting as soft, dome-shaped mounds resemblinglipomas.

Neurological and Neuropsychiatric Adverse Effects of Dermatologic Medications.

Severe, recalcitrant dermatologic conditions often require systemic treatment. Although efficacious, these medications have been associated with wide-ranging adverse reactions. Some are reversible, predictable, and either dose-dependent or treatment length-dependent, while others are unpredictable, irreversible, and potentially fatal. This review examines the neuropsychiatric adverse effects associated with US FDA-approved medications for treatment of the following dermatologic pathologies that typically require systemic therapy: autoimmune dermatoses, acne, psoriasis, and melanoma. A search of the literature was performed, with adverse effects ranging from mild headaches and neuropathy to severe encephalopathies. The medications associated with the most serious reactions were those used to treat psoriasis, especially the older non-biologic medications such as cyclosporine A and methotrexate. Given the importance of these systemic dermatologic therapies in treating severe, recalcitrant conditions, and the wide variety of potentially serious neuropsychiatric adverse effects of these medications, neurologists, psychiatrists, dermatologists, oncologists, and primary care providers must be aware of the potential for these neuropsychiatric adverse reactions to allow for appropriate counseling, management, and medication withdrawal.