Innate lymphoid cells: a new key player in atopic dermatitis.

Atopic dermatitis (AD) is a common allergic inflammatory skin condition mainly caused by gene variants, immune disorders, and environmental risk factors. The T helper (Th) 2 immune response mediated by interleukin (IL)-4/13 is generally believed to be central in the pathogenesis of AD. It has been shown that innate lymphoid cells (ILCs) play a major effector cell role in the immune response in tissue homeostasis and inflammation and fascinating details about the interaction between innate and adaptive immunity. Changes in ILCs may contribute to the onset and progression of AD, and ILC2s especially have gained much attention. However, the role of ILCs in AD still needs to be further elucidated. This review summarizes the role of ILCs in skin homeostasis and highlights the signaling pathways in which ILCs may be involved in AD, thus providing valuable insights into the behavior of ILCs in skin homeostasis and inflammation, as well as new approaches to treating AD.

Discrimination and Characterization of the Volatile Organic Compounds in Schizonepetae Spica from Six Regions of China Using HS-GC-IMS and HS-SPME-GC-MS.

Volatile organic compounds (VOCs) are the main chemical components of Schizonepetae Spica (SS), which have positive effects on the quality evaluation of SS. In this study, HS-SPME-GC-MS (headspace solid-phase microextraction-gas chromatography-mass spectrometry) and HS-GC-IMS (headspace-gas chromatography-ion mobility spectrometry) were performed to characterize the VOCs of SS from six different regions. A total of 82 VOCs were identified. In addition, this work compared the suitability of two instruments to distinguish SS from different habitats. The regional classification using orthogonal partial least squares discriminant analysis (OPLS-DA) shows that the HS-GC-IMS method can classify samples better than the HS-SPME-GC-MS. This study provided a reference method for identification of the SS from different origins.

Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate-to-severe atopic dermatitis: A network meta-analysis.

Janus kinase (JAK) inhibitors have become promising treatments for atopic dermatitis (AD), however no study directly comparing JAK inhibitors with each other has been reported. We conducted this network meta-analysis to determine the comparative efficacy and safety of three common oral JAK inhibitors including abrocitinib, baricitinib, and upadacitinib for moderate-to-severe AD. We first identified eligible studies from published meta-analyzes, then we searched PubMed to obtain additional studies published between February and July 2021. Clinical efficacy and safety were evaluated as primary and secondary outcome, respectively. After extracting data and assessing methodological quality, we utilized ADDIS 1.4 software to conduct pair-wise and network meta-analyzes. Ten eligible studies were included in the final analysis. Pooled results that abrocitinib, baricitinib, and upadacitinib obtained higher investigator global assessment (IGA), eczema area, and severity index (EASI) response, however abrocitinib and upadacitinib caused more treatment-emergent adverse events (TEAEs) regardless of doses, compared with placebo. Network meta-analyzes revealed that upadacitinib 30 mg was superior to all regimens and upadacitinib 15 mg was better than remaining regimens except for abrocitinib 200 mg in terms of IGA and EASI response. Moreover, abrocitinib 200 mg was superior to abrocitinib 100 mg, baricitinib 1 mg, 2 mg, and 4 mg for clinical efficacy. However, upadacitinib 30 mg caused more TEAEs. Abrocitinib, baricitinib, and upadacitinib were consistently effective therapies in adult and adolescent patients with AD; however, upadacitinib 30 mg may be the optimal option in short-term studies. More efforts should be done to reduce the risk of TEAEs caused by upadacitinib 30 mg.

A novel homozygous mutation in LSS gene possibly causes hypotrichosis simplex in two siblings of a Tibetan family from the western Sichuan province of China.

Aim: Hypotrichosis simplex (MIM 146520) is a rare form of monogenic hereditary alopecia. Several genes have been identified as being associated with the disease, including LPAR6, LIPH, and DSG4. LSS encoding lanosterol synthase (LSS) has been shown to cause hypotrichosis simplex, but the related mechanisms have not been elucidated to date. This study aims to find mutations in LSS from a Chinese family, among which a 21-year-old male patient and his 9-year-old sister were affected by hypotrichosis simplex. Methods: Dermoscopy and histological analysis were used to examine patients' scalps, while exome sequencing was used to find the mutations in LSS. Results: The hair loss was only detected on the scalp of the proband and his sister, while other ectodermal structures were normal with no systemic abnormalities. Further, the exome sequencing identified a new homozygous mutation NM_002340.6 (LSS_v001):c.812T>C (p.(Ile271Thr)) in the LSS gene of the proband, which was also found in his sister. In addition, a heterozygous mutation of LSS was found in their asymptomatic parents. Finally, the possible protein structure of the mutational LSS was predicted. Conclusion: The hypotrichosis simplex reported here could be an autosomal recessive disease in this family. The mutation on LSS might reduce the enzyme activity of LSS, thus leading to the disease.

Aberrant PTEN, PIK3CA, pMAPK, and TP53 expression in human scalp and face angiosarcoma.

ABSTRACT: Angiosarcoma is a rare, highly aggressive malignant tumor originating from endothelial cells that line the lumen of blood or lymphatic vessels. The molecular mechanisms of scalp and face angiosarcoma still need to be elucidated. This study aimed to investigate the expression of phosphatase and tensin homolog (PTEN), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphorylated mitogen-activated kinase-like protein (pMAPK), and tumor protein p53 (TP53) in scalp and face angiosarcoma and to assess tumor tissue apoptosis.The expression and intracellular distribution of PTEN, PIK3CA, pMAPK, and TP53 proteins in 21 specimens of human scalp and face angiosarcoma and 16 specimens of human benign hemangioma were evaluated using immunohistochemistry. Tumor cell apoptosis was assessed by terminal deoxyribonucleotide transferase-mediated dUTP nick end-labeling staining.Significantly lower PTEN but higher PIK3CA, pMAPK, and TP53 immunostaining were detected in the angiosarcoma specimens than in the benign hemangioma specimens(P < .01). The angiosarcoma tissues exhibited significantly higher apoptosis indices than the benign hemangioma tissues (P < .01). The positive expression rates of PIK3CA, pMAPK, and TP53 were correlated with the degree of tumor differentiation in the human scalp and face angiosarcoma.The PI3K, MAPK, and TP53 pathways might be involved in angiosarcoma tumorigenesis in humans and may serve as therapeutic targets for the effective treatment of this malignancy.

Changes in synchronization of the motor unit in muscle fatigue condition during the dynamic and isometric contraction in the Biceps Brachii muscle.

The fatigue-induced neuromuscular mechanism remains to be fully elucidated. So far, the macroscopic mechanism using global surface electromyogram (sEMG) has been widely investigated. However, the microscopic mechanism using high-level neural information based on motor unit (MU) spike train from the spinal cord lacks attention, especially for the conditions under dynamic contraction task. The synchronization of the MU spike train is generally assumed to be an excellent indicator to represent the activities of spinal nerves. Accordingly, this study employed synchronization of MU spike train decomposed from high-density sEMG (HD-sEMG) to investigate the fatigue condition in muscular contractions within the Biceps Brachii muscle under both isometric and dynamic contraction tasks, giving a complete picture of the microscopic fatigue mechanism. We compared the synchronization of MU in Delta (1-4 Hz), alpha (8-12 Hz), Beta (15-30 Hz), and Gamma (30-60 Hz) frequency bands during the fatigue condition induced by different contractions. Our results showed that MU synchronization increased significantly (p<0.05) in all frequency bands across the two contraction tasks. The results indicate that the microscopic fatigue mechanism of Biceps Brachii muscle does not vary due to different contraction tasks.

Clinical and pathological study on mixed tumors of the skin.

Mixed tumor of the skin (MTS) is a rare benign tumor of the sweat glands with a reported frequency of 0.01% to 0.098%. The objective of the study is to investigate clinicopathological and immunohistochemical features of mixed tumor of the skin.This was a retrospective study of 21 patients diagnosed with MTS at the Institute of Dermatology and Venereology of Sichuan Provincial People's Hospital from 1980 to 2016. Pathological sections of all cases were reread and the diagnosis was verified.There were 14 males (67%) and 7 females (33%). MTS affected the face. The lesions were skin-colored or lightly red, with no subjective symptoms in most cases. Histopathologically, the tumors consisted of epithelial and interstitial components. The epithelium was mainly composed of cubic or polygonal cells, which can be seen within the tubule-like structures with bilayer epithelium. The inner cells mainly expressed cytokeratin and other epithelial markers. The outer cells expressed epithelial and mesenchymal markers. The outer cells expressed S-100, P63, and glial fibrillary acidic protein. The tumors showed interstitial mucus-like and fibrosis changes, and some parts had cartilage-like changes.Pathological diagnosis is particularly important because the clinical symptoms of MTS lack specificity.

Therapeutic angiogenesis in ischemic muscles after local injection of fragmented fibers with loaded traditional Chinese medicine.

Therapeutic angiogenesis remains the most effective method to re-establish a proper blood flow in ischemic tissues. There is a great clinical need to identify an injectable format to achieve a well accumulation following local administration and a sustained delivery of biological factors at the ischemic sites. In the current study, fragmented nanofibers with loaded traditional Chinese medicines, astragaloside IV (AT), the main active ingredient of astragalus, and ferulic acid (FA), the main ingredient of angelica, were proposed to promote the microvessel formation after intramuscular injection into ischemic hindlimbs. Fragmented fibers with average lengths of 5 (FF-5), 20 (FF-20) and 80 µm (FF-80) were constructed by the cryocutting of aligned electrospun fibers. Their dispersion in sodium alginate solution (0.2%) indicated good injectability. After injection into the quadriceps muscles of the hindlimbs, FF-20 and FF-80 fiber fragments showed higher tissue retentions than FF-5, and around 90% of the injected doses were determined after 7 days. On a hindlimb ischemia model established by ligating the femoral arteries, intramuscular injection of the mixtures of FA-loaded and AT-loaded FF-20 fiber fragments substantially reduced the muscle degeneration with minimal fibrosis formation, significantly enhanced the neovessel formation and hindlimb perfusion in the ischemic tissues, and efficiently promoted the limb salvage with few limb losses. Along with the easy manipulation and lower invasiveness for in vivo administration, fragmented fibers should become potential drug carriers for disease treatment, wound recovery and tissue repair after local injection.

An analysis of the Malassezia species distribution in the skin of patients with pityriasis versicolor in Chengdu, China.

Pityriasis versicolor (PV) is a common clinical problem associated with Malassezia species (Malassezia spp.). Controversies remain regarding the specific species involved in the development of PV. This study analyzed the difference in Malassezia spp. distribution in lesional and nonlesional skin in Chinese PV patients. A paired design was applied. Lesional and nonlesional scales from 24 cases were collected; real-time fluorescence quantitative PCR was used to detect 10 different Malassezia spp. In lesional skin, the highest detection rates were for M. globosa (95.8%), M. restricta (91.7%), and M. sympodialis (50.0%). In nonlesional skin, the highest detection rates were for M. globosa (87.5%), M. restricta (79.2%), and M. dermatis (33.3%). A significant difference in the detection rate was only found for M. sympodialis (50.8% versus 20.8%, P = 0.04). Compared with nonlesional skin, the amount of M. globosa, M. restricta, and M. sympodialis in lesional skin was significantly higher (3.8 ± 1.3, 2.5 ± 1.1, and 3.2 ± 1.6 times higher, resp.). The results of this study do not indicate that M. globosa and M. restricta are directly correlated with PV development; however, M. sympodialis is more likely related to PV development in Chinese individuals.

Mucor irregularis infection around the inner canthus cured by amphotericin B: a case report and review of published literatures.

We report a case of primary cutaneous mucormycosis caused by Mucor irregularis. A 47-year-old farmer was presented to our clinic with the history of progressive red plaque around the inner canthus following dacryocystectomy about a year earlier. Linear, aseptate hyphae were seen by direct KOH examination and in biopsy. Fungal culture revealed light yellow filamentous colonies that were identified as Mucor irregularis by nucleotide sequencing of rRNA gene. Amphotericin B and dexamethasone were used in gradually increasing dosage. The treatment lasted 43 days, and the patient received 760 mg total amphotericin B. The patient was discharged after 2 months of treatment. The plaque became smooth, and fungal culture was negative. There was no recurrence for half a year through telephone follow-ups. A review of published studies revealed 23 cases of Mucor irregularis infection. Most cases resulted following injuries or surgical complications. Farmers and manual laborers were most at risk with males outnumbering females among patients. Amphotericin B and its liposomal preparations remain most effective treatment choices.

Promoted regeneration of mature blood vessels by electrospun fibers with loaded multiple pDNA-calcium phosphate nanoparticles.

Vascularization is one of the capital challenges in the establishment of tissue engineering constructs and recovery of ischemic and wounded tissues. The aim of this study was to assess electrospun fibers with loadings of multiple pDNA to allow a localized delivery for an efficient regeneration of mature blood vessels. To induce sufficient protein expression, a reverse microemulsion process was adopted to load pDNA into calcium phosphate nanoparticles (CP-pDNA), which were electrospun into fibers to achieve a sustained release for 4 weeks. Compared with pDNA-infiltrated fibers, the localized and gradual release of pDNA facilitated cell proliferation, gene transfection, and extracellular matrix secretion and enhanced the generation of blood vessels after subcutaneous implantation. Compared with commonly used pDNA polyplexes with poly(ethyleneimine), CP-pDNA nanoparticles induced significantly lower cytotoxicity and less inflammation reaction after implantation into animals. Fibers with encapsulated nanoparticles containing plasmids encoding vascular endothelial growth factor (pVEGF) and basic fibroblast growth factors (pbFGF) led to significantly higher density of mature blood vessels than those containing individual plasmid. It is suggested that the integration of CP-pDNA nanoparticles with loadings of multiple plasmids into fibrous scaffolds should provide clinical relevance for therapeutic vascularization, getting fully vascularized in engineered tissues and regeneration of blood vessel substitutes.

Two novel mutations on exon 8 and intron 65 of COL7A1 gene in two Chinese brothers result in recessive dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa is an inherited bullous dermatosis caused by the COL7A1 gene mutation in autosomal dominant or recessive mode. COL7A1 gene encodes type VII collagen - the main component of the anchoring fibrils at the dermal-epidermal junction. Besides the 730 mutations reported, we identified two novel COL7A1 gene mutations in a Chinese family, which caused recessive dystrophic epidermolysis bullosa (RDEB). The diagnosis was established histopathologically and ultrastructurally. After genomic DNA extraction from the peripheral blood sample of all subjects (5 pedigree members and 136 unrelated control individuals), COL7A1 gene screening was performed by polymerase chain reaction amplification and direct DNA sequencing of the whole coding exons and flanking intronic regions. Genetic analysis of the COL7A1 gene in affected individuals revealed compound heterozygotes with identical novel mutations. The maternal mutation is a 2-bp deletion at exon 8 (c.1006_1007delCA), leading to a subsequent reading frame-shift and producing a premature termination codon located 48 amino acids downstream in exon 9 (p.Q336EfsX48), consequently resulting in the truncation of 2561 amino acids downstream. This was only present in two affected brothers, but not in the other unaffected family members. The paternal mutation is a 1-bp deletion occurring at the first base of intron 65 (c.IVS5568+1delG) that deductively changes the strongly conserved GT dinucleotide at the 5' donor splice site, results in subsequent reading-through into intron 65, and creates a stop codon immediately following the amino acids encoded by exon 65 (GTAA→TAA). This is predicted to produce a truncated protein lacking of 1089 C-terminal amino acids downstream. The latter mutation was found in all family members except one of the two unaffected sisters. Both mutations were observed concurrently only in the two affected brothers. Neither mutation was discovered in 136 unrelated Chinese control individuals. This study reveals novel disease-causing mutations in the COL7A1 gene.

An unusual case of granulomatous lymphadenitis due to Prototheca zopfii var. portoricensis in an immunocompetent man in China.

BACKGROUND: Protothecosis is an uncommon human infection caused by Prototheca. Prototheca spp can be considered as saprophytes, and in spite of their frequency in the environment, they are of low virulence and may cause chronic infection with low-grade inflammation in humans. At present, only three species are recognized: Prototheca wickerhamii, Prototheca zopfii and Prototheca stagnora. Of these, the former two have been associated with human disease. This study was an investigation of the clinical and microbiological features of a case of granulomatous lymphadenitis due to P. zopfii var. portoricensis in an immunocompetent man in China. METHODS: We report the case of a 39-year-old male, who presented with swollen lymph nodes, from which the organism was isolated and identified by the RapidID Yeast Plus test (Remel, Santa Fe, NM, USA) and PCR molecular analysis. The pathogenicity of the isolate was confirmed in a mouse model and antifungal drug susceptibility testing was carried out. RESULTS: The pathogen was identified as Prototheca zopfii. The DNA sequence of the 18S SSU rDNA regions of the isolate strain were 100% (1205/1205) identical with Prototheca zopfii var. portoricensis. Antifungal susceptibility tests revealed that it was sensitive to amphotericin B, but resistant to 5-flucytosine, fluconazole, ketoconazole, and itraconazole. The patient responded to treatment with intravenous itraconazole and amphotericin B. CONCLUSIONS: Based on the patient's symptoms and microscopic evaluation, cultures, and molecular analyses of the isolate, granulomatous lymphadenitis due to P. zopfii var. portoricensis was diagnosed. P. zopfii var. portoricensis as a causative agent of human lymphadenitis in an immunocompetent case has not been reported, though a few cases of protothecosis have been reported in China. The real number of protothecosis cases may be greater than that reported in the literature. Thus, clinicians should be vigilant for any unknown cause of granulomatous lymphadenitis and should undertake an intensive histopathology, mycology examination, and even molecular analysis to rule out or confirm a potential Prototheca infection.