The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient’s adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread.

Macrophages, a kind of innate immune cells, derive from monocytes in circulation and play a crucial role in the innate and adaptive immunity. Under the stimulation of the signals from local microenvironment, macrophages generally tend to differentiate into two main functional phenotypes depending on their high plasticity and heterogeneity, namely, classically activated macrophage (M1) and alternatively activated macrophage (M2). This phenomenon is often called macrophage polarization. In pathological conditions, chronic persistent inflammation could induce an aberrant response of macrophage and cause a shift in their phenotypes. Moreover, this shift would result in the alteration of macrophage polarization in some vascular dermatoses; e.g., an increase in proinflammatory M1 emerges from Behcet’s disease (BD), psoriasis, and systemic lupus erythematosus (SLE), whereas an enhancement in anti-inflammatory M2 appears in infantile hemangioma (IH). Individual polarized phenotypes and their complicated cytokine networks may crucially mediate in the pathological processes of some vascular diseases (vascular dermatosis in particular) by activation of T cell subsets (such as Th1, Th2, Th17, and Treg cells), deterioration of oxidative stress damage, and induction of angiogenesis, but the specific mechanism remains ambiguous. Therefore, in this review, we discuss the possible role of macrophage polarization in the pathological processes of vascular skin diseases. In addition, it is proposed that regulation of macrophage polarization may become a potential strategy for controlling these disorders.

Objective The aim of this research was to systematically investigate the effects of endothelial mesenchymal transition (EndMT) induced by hypoxia on the skin microvascular remodeling of systemic sclerosis (SSc) and the underlying mechanism. Methods Skin tissues from SSc patients and controls were collected for isobaric tags for the relative and absolute quantification (iTRAQ)-based proteomics and immunohistochemical test. Human microvascular endothelial cell line-1 (HMEC-1) cultured in hypoxic or normal conditions was treated by tamoxifen or bevacizumab. Results The iTRAQ-based proteomics indicated a significantly upregulated hypoxia-inducible factor-1 (HIF-1) signal in SSc samples. The immunohistochemical results demonstrated the significant downregulation of CD31, the positive staining of α-smooth muscle actin (α-SMA), HIF-1α, and vascular endothelial growth factor (VEGF-a) in SSc skin tissues, compared with control samples. Consistent with these observations, HMEC-1 cells cultured under hypoxic conditions exhibited a significant decrease in CD31 and VE-cadherin expression, alongside a marked increase in the expression of α-SMA and fibronectin, as well as a distinct upregulation of HIF-1α and VEGF-a, when compared with those under normal conditions. It is noteworthy that the inhibition of HIF-1α by tamoxifen effectively downregulated the hypoxic induction of VEGF-a and α-SMA while rescuing the hypoxic suppression of CD31. In addition, the VEGF-a inhibitor bevacizumab treatment had the same effect on the hypoxic expression of α-SMA and CD31, as a tamoxifen intervention, but did not reduce HIF-1α. Conclusion These results suggest that the HIF-1α/VEGF signaling pathway can have a critical role in mediating the effect of hypoxia-induced EndMT on the skin microvascular remodeling of SSc.

Background and Objectives The skin microbiota partly determined by epidermal barrier plays an important role in acne vulgaris and intense pulsed light (IPL) has been verified as a safe and effective therapeutic option for this disease. Nevertheless, the exact role of the IPL treatment on the skin microbiota and epidermal barrier for patients with acne vulgaris remains unclear. This article was designed to solve this problem. Study Design/Materials and Methods Nineteen healthy controls and 20 patients with mild to moderate acne were enrolled in this study, who received IPL treatment for 12 weeks. The epidermal barrier and skin samples were collected at baseline and after treatment. The microbial diversity was analyzed based on a high‐throughput sequencing approach, which targets the V3–V4 region of the bacteria 16S ribosomal RNA genes. Results After treatment of IPL, the Global Acne Grading System (GAGS) scores, sebum, sclererythrin, and red area of patients were significantly improved by IPL treatment (P < 0.05). Although there was no difference in microbiota diversity before and after IPL treatment, the Nonmetric Multidimension Scaling (NMDS) analysis showed that the samples of the acne patients before and after treatment could be divided into two different sets by skin microbiota (P = 0.011), which could be verified by heatmap analysis. Moreover, we found that the relative abundance of Staphylococcus epidermidis (S. epidermidis) significantly increased, but Cutibacterium acnes (C. acnes) decreased after IPL treatment. The sebum concentration was positively correlated with PH value (R = 0.525, P = 0.017), and the GAGS was positively associated with both sclererythrin (R = 0.477, P = 0.002) and red area (R = −0.503, P = 0.001). Conclusions IPL could successfully improve the GAGS scores of acne vulgaris, as well as regulate the equilibrium between C. acnes and S. epidermidis, and inhibit the sebum secretion. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Senile pruritus (SP) can be defined as chronic pruritus of unknown origin 1 or pruritus without a primary lesion, which occurs in the elderly aged over 60 years and lasting for at least 6 weeks. 2 The prevalence of SP has been reported to increase with age, with a 20.8% incidence in people aged 60-69 years, 22.9% in 70-79 years, and 26% in 75 years and over. 3,4 It is known that the adverse effect of chronic pruritus on quality of life is similar to that of chronic pain, which could contribute to depression of patients due to sleep disorders and other causes. 5 It was found that ordinary patients were willing to lose 13% of life expectancy to live without

Background: Endothelial mesenchymal transition (EndMT) is a key pathological event for vasculopathy, and is one of the early features and hallmarks of systemic scleroderma (SSc). It has been well-established that hypoxia contributes to EndMT. However, little is known about the effects of EndMT induced by hypoxia on the skin microvascular remodeling of SSc, as well as the underlying mechanism. Methods: Skin biopsy was performed for SSc patients and healthy controls, and skin tissues were collected for isobaric tags for the relative and absolute quantification (iTRAQ)-based proteomics and immunohistochemical test. Human microvascular endothelial cell line-1 (HMEC-1) cultured in hypoxic or normal conditions was treated by tamoxifen or bevacizumab. The expression of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF)-a, CD31, α-smooth muscle actin (α-SMA), VE-cadherin, and fibronectin were detected at both the protein and mRNA level.Results: The iTRAQ-based proteomics indicated the significantly upregulated HIF-1 signal in the skin tissues of SSc patients. The immunohistochemical results demonstrated the significant downregulation of endothelial cell (EC) marker CD31 and the distinct positive staining of interstitial cell (IC) marker α-SMA at sites that lined the vessel lumens in skin tissues of SSc. Meanwhile, the positive staining of HIF-1α, which is a key transcription factor in response to chronic hypoxia, and VEGF-a were found to be diffusely distributed in SSc skin tissues. Consistent with these observations, HMEC-1 cells cultured under hypoxic conditions exhibited a significant decrease in CD31 and VE-cadherin expression, alongside the marked increase in the expression of α-SMA and fibronectin, as well as the distinct upregulation of HIF-1α and VEGF-a, when compared with those under normal conditions. It is noteworthy that the inhibition of HIF-1α by tamoxifen effectively downregulated the hypoxic induction of VEGF-a and α-SMA, while rescuing the hypoxic suppression of CD31. In addition, the VEGF-a inhibitor bevacizumab treatment had the same effect on the hypoxic expression of α-SMA and CD31, as a tamoxifen intervention, but did not reduce HIF-1α. Conclusion: These results suggest that the HIF-1α/VEGF signaling pathway has a critical role in mediating the effect of hypoxia-induced EndMT on the skin microvascular remodeling of SSc.

Background: Endothelial mesenchymal transition (EndMT) is a key pathological event for vasculopathy which is one of the early features and hallmarks of systemic scleroderma (SSc). It is well established that hypoxia contributes to EndMT, however, little is known about the effects of EndMT induced by hypoxia on skin microvascular remodeling of SSc,as well as the underlying mechanism.Methods: Skin biopsy was down for SSc patients and healthy controls and skin tissues were collected for iTRAQ-based proteomics and Immunohistochemical test. Human microvascular endothelial cell line (HMEC-1) cultured with hypoxic or normal conditions, treated by either tamoxifen or bevacizumab. The expression of Hypoxia inducible factor-1α (HIF-1α) ,vascular endothelial growth factor (VEGF)-a, CD31, α-smooth muscle actin (α-SMA), VE-cadherin, fibronectin were detected at both protein and mRNA level.Results : The iTRAQ-based proteomics indicated significantly up-regulated HIF-1 sigaling in the skin tissues of SSc patients. Immunohistochemical results demonstrated a significant downregulation of the endothelial cell (EC) marker CD31 and a distinct positive staining of the interstitial cell (IC) marker α-SMA at sites lining the vessel lumens in the skin tissues of SSc. Meanwhile the positive staining of HIF-1α, a key transcription factor in response to chronic hypoxia, and VEGF-a were found to be diffusely distributed in SSc skin tissue. Consistent with these observations, HMEC-1 cells cultured under hypoxic conditions exhibited a significant decrease in CD31 and VE-cadherin expression, alongside a marked increase in the expression of α-SMA and fibronectin, as well as a distinct up-regulation of HIF-1α and VEGF-a, while comparing with them under normal condition. Of note, the inhibition of HIF-1α by tamoxifen effectively down-regulated the hypoxic induction VEGF-a, α-SMA, while rescuing hypoxic suppression of CD31. In addition, a VEGF-a inhibitor bevacizumab treatment had the same effect on the hypoxic expression of α-SMA and CD31 as tamoxifen intervention, but did not reduce HIF-1α.Conclusion: These results suggest that the HIF-1α/VEGF signaling pathway has a critical role in mediating the effect of hypoxia-induced EndMT on skin microvascular remodeling of SSc.