Increase in the incidence of invasive fungal infections due to Volvariella Volvacea.

PURPOSE: We aimed to show the increasing incidence of invasive fungal infections due to Volvariella Volvacea in patients with immunosuppression. METHODS: We present a case of an invasive fungal infection caused by Volvariella volvacea, and summarize the clinical and pathological features based on this case and a review of the literature. RESULTS: A total of seven patients with IFIs due to Volvariella Volvacea have been reported in the literature. The majority of cases have been obtained between 2019 and 2022. Including our case, they all had acquired immunosuppression. The lung and brain were the most commonly affected organs. All eight of these patients received antifungal therapy, but five still died one to seven months after occurrences of IFIs. CONCLUSION: The incidence of invasive fungal infections due to Volvariella Volvacea is increasing in recent years. It mainly occurred in patients with immunosuppression, especially in patients with malignant hematological cancers, and increased mortality.

Tumor necrosis factor-α inhibitor for successful treatment of toxic epidermal necrolysis with severe infection: a case series.

Toxic epidermal necrolysis (TEN) is a rare severe cutaneous adverse reaction that involves more than 30% of the body surface area. TEN can be accompanied by a series of systemic symptoms and has a high risk of death. Tumor necrosis factor (TNF)-α inhibitors such as adalimumab and etanercept have been shown to be safe and effective for the treatment of TEN in some cases. However, clinical data on the use of TNF-α inhibitors to treat TEN with severe systemic infection are scarce. In the present study, three adult patients who developed TEN with serious active infection were successfully treated with etanercept. One of the three patients had active open pulmonary tuberculosis, and the other two had septicemia and/or fungal sepsis. All patients' skin lesions significantly improved after several days, and none of the patients developed emerging or re-emerging infectious diseases, adverse reactions, or a similar rash during follow-up. TNF-α inhibitors may be an effective treatment choice for TEN with severe systemic infection. However, further studies with large samples are still required for validation because clinical experience is limited.

Rapamycin protects mouse skin from ultraviolet B-induced photodamage by modulating Hspb2-mediated autophagy and apoptosis.

BACKGROUND: Continuous exposure to UVB is the main extrinsic cause of skin photodamage, which is associated with oxidative stress, DNA damage, apoptosis and degradation of collagen. Rapamycin, a mechanistic target inhibitor of rapamycin complex 1 (mTORC1), has been shown to play a crucial role anti-tumor and aging retardation, but its mechanism of action in UVB-induced photodamage still remains unknown. In this study, we investigated the role of rapamycin and Hspb2 (also known as Hsp27) in UVB-induced photodamage in mice. METHODS AND RESULTS: We constructed skin acute photodamage models on the ears of WT and Hspb2 KO mice, respectively, and administered rapamycin treatment. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels, with a significant increase in p53 levels and Bax/Bcl-2 ratio, a reduction in LC3II/I ratio and an increase in p62 levels in the KO mice compared to those in WT mice after the same dose of UVB irradiation. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. CONCLUSIONS: Rapamycin can alleviate skin photodamage from Hspb2 knockout to some extent. It may be a potential therapeutic drug for skin photodamage. In this study, we investigated the role of rapamycin and Hspb2 in UVB-induced photodamage in mice. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-ß/Smad signaling pathway. We conclude that rapamycin and Hspb2 exert a synergistic protective effect in skin photodamage.

A Patient with Adalimumab-Induced Refractory Paradoxical Palmoplantar Pustulosis Was Successfully Treated by Ixekizumab: A Case Report.

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disorder involving the sacroiliac (SI) joints, the spine and often the hips. Biologic therapy has been shown to be efficacious in patients with AS and could improve patients' quality of life. With the increased use of tumor necrosis factor-ɑ (TNF-ɑ) inhibitors, more paradoxical reactions have been revealed. However, the treatment option for patients with AS is still a challenge when refractory paradoxical palmoplantar pustulosis appeared after the use of TNF-ɑ inhibitors. We reported the case of a 45-year-old male patient with AS treated with adalimumab treatment who developed a refractory paradoxical palmoplantar pustulosis after failure of prior secukinumab treatment. A dramatic improvement was seen in all skin and low back pain after the use of ixekizumab. We conclude that, in TNF-α inhibitors induced refractory paradoxical palmoplantar pustulosis, ixekizumab should be considered as an alternative option to choose from.

Predicting the Risk of Nail Involvement in Psoriasis Patients: Development and Assessment of a Predictive Nomogram.

BACKGROUND: Nail involvement has a tremendous impact on psoriasis patients. Early detection and prompt intervention of psoriatic nail damage are necessary. METHODS: A total of 4290 patients confirmed to have psoriasis between June 2020 and September 2021 were recruited from the Follow-up Study of Psoriasis database. Among them, 3920 patients were selected and divided into the nail involvement group (n = 929) and the non-nail involvement group (n = 2991) by inclusion and exclusion criteria. Univariate and multivariable logistic regression analyses were performed to identify the predictors of nail involvement for the nomogram. Calibration plots, the receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the discriminative and calibrating ability and clinical utility of the nomogram. RESULTS: Sex, age at onset, duration, smoking, drug allergy history, comorbidity, sub-type of psoriasis, scalp involvement, palmoplantar involvement, genital involvement, and PASI score were selected to establish the nomogram for nail involvement. AUROC (0.745; 95% CI: 0.725-0.765) indicated the satisfactory discriminative ability of the nomogram. The calibration curve showed favorable consistency, and the DCA showed the good clinical utility of the nomogram. CONCLUSION: A predictive nomogram with good clinical utility was developed to assist clinicians in evaluating the risk of nail involvement in psoriasis patients.

HSP27 Protects Skin From Ultraviolet B -Induced Photodamage by Regulating Autophagy and Reactive Oxygen Species Production.

Ultraviolet (UV) irradiation has been well documented to be linked with almost all skin problems we know, and both dermis and epidermis may be affected to varying degrees by UV irradiation. Every time when exposed to sunlight without protection, our skin will step closer to photoaging, leading to irreversible consequences ultimately. Heat shock protein 27 (HSP27) is a vital protein involved in cell growth, autophagy, apoptosis, drug resistance, tumor genesis and metastasis. Evidence suggests that the organism is subjected to various internal and external environmental stresses (heat, oxidative stress, organic toxicants, etc.), and HSP27 with high expression has protective function. However, the expression of HSP27 in coping with UV irradiation have not been examined thoroughly. In this study, photodamage models were developed through different doses of UVB irradiation in human epidermal keratinocytes (HEKs) (30 mJ/cm2), human dermal fibroblasts (HDFs) (150 mJ/cm2) and mouse skin (2,700 mJ/cm2). HSP27 knockdown decreased cell viability and increased the incidence of UVB-induced reactive oxygen species (ROS) production. We got consistent results in vivo and vitro. Compared with that in the UVB group, the expression of LC3B was significantly lower, while the expression of p62 was significantly higher in the UVB + si-HSP27 group. It was also revealed that HSP27 knockdown reduced the expressions of some antioxidants, such as superoxide dismutase (SOD) and catalase (CAT), which accelerated UVB-induced ROS release. Moreover, histological results showed that epidermis was thickened and collagen fibers were disorganized in the UVB + si-HSP27 group. These findings have demonstrated that HSP27 might play a photoprotective role in the UVB-induced skin damage process by maintaining the normal autophagy and antioxidant level. It is implied that HSP27 could be a potential therapeutic target of photodamage. However, determination of the definitive mechanism requires further exploration.

Risk factors related to postoperative recurrence of dermatofibrosarcoma protuberans: A retrospective study and literature review.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade malignant soft tissue tumor characterized by rosette-like infiltrative growth. Postoperative recurrence of this tumor is very common. AIM: To evaluate the risk factors related to recurrence after wide local excision (WLE) of DFSP and to guide clinical diagnosis and treatment. METHODS: The medical records of 44 DFSP patients confirmed by pathology at our hospital from 2012 to 2019 were retrospectively reviewed. The relationship between clinical features, tumor characteristics, treatment, and recurrence risk were analyzed, and the possible risk factors for postoperative tumor recurrence were evaluated. RESULTS: There were 44 patients in total, including 21 males and 23 females. The median progression free survival was 36 mo (range, 1-240 mo). Twenty patients were treated for the first time, while 24 had previous treatment experience. Forty-two cases were followed for 25.76 ± 22.0 mo, among whom four (9.52%) experienced recurrence after WLE (rate was 9.52%). The recurrence rate in the recurrent group was higher than that in the patients with primary tumor (19.05% vs 0%, P = 0.028). Eighteen cases had a history of misdiagnosis (rate was 40.91%). The recurrence rate among patients with previous experience of misdiagnosis was significantly higher than in patients without (68% vs 36.84%, P = 0.04). The tumor diameter in patients with a history of treatment was larger than in patients treated for the first time (4.75 ± 0.70 cm vs 2.25 ± 0.36 cm, P = 0.004). CONCLUSION: To sum up, the clinical manifestations of DFSP are not specific and are easily misdiagnosed, thus commonly causing the recurrence of DFSP. After incomplete resection, the tumor may rapidly grow. Previous recurrence history may be a risk factor for postoperative recurrence, and tumor location may have an indirect effect on postoperative recurrence; however, we found no significant correlation between sex, age, course of the disease, or tumor size and postoperative recurrence.

The HSP90 Inhibitor, 17-AAG, Influences the Activation and Proliferation of T Lymphocytes via AKT/GSK3ß Signaling in MRL/lpr Mice.

OBJECTIVE: To explore the molecular mechanism of 17-AAG in the treatment of systemic lupus erythematosus (SLE), and the effects of the heat shock protein 90 (HSP90) inhibitor 17-AAG on the activation and proliferation of lymphocytes and the AKT/GSK3ß signaling pathway in MRL/lpr mice were detected. METHODS: MRL/lpr mice were randomly divided into the control group and the experimental group. The experimental group was injected intraperitoneally with 17-AAG, and T lymphocytes were separated by magnetic beads. Lymphocyte proliferation was detected by MTT and flow cytometry (FCM), and the expression of the HSP90 protein and PI3K/AKT signaling pathway-related proteins was detected by Western blotting. Renal histopathology and immune complex deposition were also observed in both groups. RESULTS: Immune complex deposition and inflammation decreased in kidneys from MRL/lpr mice in the experimental group. HSP90 protein expression, T lymphocyte proliferation and phosphorylated AKT and GSK3ß levels also decreased in the experimental group. CONCLUSION: 17-AAG can inhibit the activation and proliferation of T lymphocytes and downregulate the AKT/GSK3ß signaling pathway, which may be relevant for the treatment of SLE.

Interference of Hsp27 Results in Apoptosis Induced by Photodamage via Regulation of Subcellular Localization of p21 in Immortalized Human Keratinocytes.

BACKGROUND Owing to the increased incidence of photodermatosis caused by ultraviolet light in recent years, it is necessary to clarify the mechanisms potential photodamage to the skin and reveal possible therapeutic targets. Heat shock protein 27 (Hsp27) is well known for suppressing apoptosis. The aim of present study was to elucidate possible photoprotective mechanism between Hsp27 and p21 on ultraviolet B (UVB)-induced photodamage. MATERIAL AND METHODS The Hsp27 gene was interfered to assess the expression of its downstream effectors, cell apoptosis, and cell proliferation ability. The cell apoptosis was tested using flow cytometry method. The cell proliferation ability was tested using Cell Counting Kit-8 (CCK-8) assay. The expression of protein was tested using western-blotting method. The expression of mRNA was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The subcellular localization was elucidated using immunofluorescence. RESULTS Hsp27 knockdown decreased cell viability and increased the incidence of UVB-induced apoptosis. Compared with control group, activation of phosphorylated-Akt (p-Akt)-dependent pathway resulted in the nuclear accumulation of p21 and suppression of cell proliferation, while promoting apoptosis in Hsp27 knockdown group. In addition, Hsp27 knockdown increased p53 expression and the Bax: Bcl-2 ratio, which further accelerated the apoptotic process. CONCLUSIONS These findings complemented the mechanism of skin photodamage and demonstrated the photoprotective mechanisms of Hsp27 in HaCaT cells, which might implicate a potential therapeutic target of photodamage and photodermatosis.

Anti-H7N9 avian influenza A virus activity of interferon in pseudostratified human airway epithelium cell cultures.

BACKGROUND: Since H7N9 influenza A virus (H7N9) was first reported in 2013, five waves of outbreaks have occurred, posing a huge threat to human health. In preparation for a potential H7N9 epidemic, it is essential to evaluate the efficacy of anti-H7N9 drugs with an appropriate model. METHODS: Well-differentiated pseudostratified human airway epithelium (HAE) cells were grown at the air-liquid interface, and the H7N9 cell tropism and cytopathic effect were detected by immunostaining and hematoxylin-eosin (HE) staining. The H7N9 replication kinetics and anti-H7N9 effect of recombinant human α2b (rhIFN-α2b) and rhIFN-λ1 were compared with different cell lines. The H7N9 viral load and interferon-stimulated gene (ISG) expression were quantified by real-time PCR assays. RESULTS: H7N9 could infect both ciliated and non-ciliated cells within the three-dimensional (3D) HAE cell culture, which reduced the number of cilia and damaged the airways. The H7N9 replication kinetics differed between traditional cells and 3D HAE cells. Interferon had antiviral activity against H7N9 and alleviated epithelial cell lesions; the antiviral activity of rhIFN-α2b was slightly better than that of rhIFN-λ1. In normal cells, rhIFN-α2b induced a greater amount of ISG expression (MX1, OAS1, IFITM3, and ISG15) compared with rhIFN-λ1, but in 3D HAE cells, this trend was reversed. CONCLUSIONS: Both rhIFN-α2b and rhIFN-λ1 had antiviral activity against H7N9, and this protection was related to the induction of ISGs. The 3D cell culture model is suitable for evaluating interferon antiviral activity because it can demonstrate realistic in vivo-like effects.

[Palmitoylation of heat shock protein 90 in mouse sperm].

Protein palmitoylation, one of post-translation modifications, refers to the addition of saturated 16-carbon palmitic acid to cysteine residues via the thioester bond. It plays key roles in various functional activities, such as the interaction, stability and location of proteins. Heat shock protein 90 (Hsp90), an important molecular chaperone, has been reported to be involved in sperm capacitation. However, it remains unclear whether protein palmitoylation exists in sperm and whether Hsp90 in sperm is palmitoylated under different physiological conditions. In this study, we examined whether the protein palmitoylation is present in mouse cauda epididymis sperm using acyl-biotin exchange method, predicted the potential palmitoylated sites of Hsp90 by the software CSS-Palm 4.0 and detected the palmitoylated Hsp90 in the mouse sperm from caput epididymis and cauda epididymis by immunoprecipitation. We found that some proteins, approximately 50, 65, 72, 85 and 130 kDa, were palmitoylated in mouse cauda epididymis sperm. Five sites in two Hsp90 isoforms were predicted to be palmitoylated. The results also showed that Hsp90 in mouse sperm was palmitoylated and its palmitoylation level was involved in different physiological conditions: the palmitoylation level of cauda epididymis sperm was higher than that of caput epididymis sperm; and the palmitoylation level after capacitation was much higher than that before capacitation. In conclusion, this study reveals that protein palmitoylation is present in mouse sperm and the palmitoylated Hsp90 is associated with different physiological conditions in sperm.

Cutaneous and systemic plasmacytosis on the face: Effective treatment of a case using thalidomide.

Cutaneous and systemic plasmacytosis is an exceedingly rare condition that is identified in Japanese individuals in particular. The present study describes the case of a patient of mainland Chinese origin who manifested with red-brown macules, papules and plaques limited to the face. Identifying a therapy for cutaneous and systemic plasmacytosis is quite difficult, however, the present patient showed a good response to low-dose thalidomide. The exact mechanism of action is not yet clear, however, we hypothesize that thalidomide may function through decreasing the secretion of interleukin-6 and affecting the growth of plasma cells.

[Establishment and evaluation of methods for determinating cystic fibrosis transmembrane conductance regulator quantitatively].

OBJECTIVE: To establish and evaluate a BA-ELISA method for the quantitative detection of cystic fibrosis transmembrane conductance regulator (CFTR) protein. METHODS: We deliberately selected three tables of CFTR and made the synthetic peptide be expressed in E. coli, then used the antigen to immunize rabbits to obtain the anti-CFTR polyclonal serum. After that, 96 well plates were coated with the purified antibody against CFTR. The antigen CFTR which was extracted from human sperm was detected by anti-CFTR antibody labeled with biotin, horseradish peroxidase conjugated avidin, and the substrate. The concentrations of two kinds of antibodies and the experiment parameters were optimized. Thereby, the double antibody sandwich BA-ELISA method for the quantitative detection of CFTR protein was established. Furthermore, the reproducibility, specificity and so on were evaluated by clinical specimens of sperm. RESULTS: The optimal concentration of coated anti-CFTR IgG was 4 µg/ml, while the biotin labeled anti-CFTR IgG was 10 µg/ml; the optimal blocking buffer was 1% BSA-PBST, the optimal time of the reaction between antigen and antibody was 60 min, the optimal chromogenic time was 15 min, the intra-assay and inter-assay coefficient were 2.16%-9.23% and 2.29%-11.71% respectively; The lowest detectable limit was 0.15 ng/ml; the standard curve had a good linear correlation of R2 = 0.962. CONCLUSION: The BA-ELISA method for the quantitative detection of CTFR protein is successfully established, and it is demonstrated that the method has strong specificity, high sensitivity and good reproducibility. It provides the basis and evidence of the further application of the method.

Health-related quality of life in patients with primary cutaneous amyloidosis.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a relatively rare and itchy skin disorder characterized by amyloid deposits in the superficial dermis. The cosmetic disfigurement and severe pruritus dramatically affects the patient's quality of life. In spite of the prevalence of the disease in China, the quality of life (QoL) impact of the PCA has not been well defined and is the focus of this study. OBJECTIVE: To examine the HRQoL of patients with PCA and to evaluate the association between HRQoL scores, disease, and socio-demographic determinants. METHODS: A total of 104 PCA patients and 101 healthy participants completed the questionnaires. HRQoL was measured using dermatology life quality index (DLQI) and SF-36. The socio demographic and clinical data such as age, sex, duration of disease and distribution of lesion pattern were analyzed mainly by hierarchical multiple regression analyses. RESULTS: Patients with PCA experienced significantly impaired health-related quality of life. The mean DLQI score was 9.05. Younger age, female gender, more pruritus and distribution pattern were independent predictor correlates of the high DLQI scores. The PCA group showed significantly decreasing average scores in several aspects of psychological symptoms, including SF, RE and MH. CONCLUSIONS: PCA disease has a negative impact on the HRQoL of patients, and the HRQoL is associated with various disease characteristics. In conjunction with medical interventions, psychological and sociocultural assessment and intervention should be an essential part of the management of these cases.

Successful treatment of necrobiotic xanthogranuloma with total glucosides of paeony.

Necrobiotic xanthogranuloma (NXG) is a rare granulomatous condition that is often associated with a paraproteinemia and in some cases multiple myeloma. We report a case of isolated NXG that responded very well to total glucosides of paeony treatment. Characteristic clinical and histological features of NXG are presented, as well as a discussion regarding management and the use of glucosides of paeony. Treatment with total glucosides of paeony is an effective, safe treatment, which avoids the side effects associated with systemic corticosteroid or cytotoxic agent therapy.

Successful Treatment of Vasculo-Behcet's Disease Presenting as Recurrent Pseudoaneurysms: the Importance of Medical Treatment.

INTRODUCTION: Vasculo-Behcet's disease is a subtype of Behcet's disease, characterized by cases in which vascular complications are present and often dominate the clinical features. In this disease, there are four different vascular complications: arterial occlusion, arterial aneurysm or pseudoaneurysm, venous thrombosis, and variceal formation. It is rare that arterial lesions are multiple, but without venous involvement. So far, the optimal treatment of the disease has not been established. CASE REPORT: The authors report a rare case of vasculo-Behcet's disease with multiple and recurrent pseudoaneurysms in large arteries, but without affecting the venous system. The patient underwent three rounds of surgery, but developed a new pseudoaneurysm after each operation in short term. However, the patient was successfully treated with a combination of prednisone and immunosuppressive agents. CONCLUSION: For Vasculo-Behcet's disease, surgical and endovascular interventions alone increased the incidence of pseudoaneurysm. Early diagnosis and early initiation of prednisone in combination with immunosuppressive therapy are critical for inhibiting the progression of vascular lesions and provide a good prognosis.

[Expression of mucin regulated by recombinant human interleukin-6 in HT-29 cell of colon cancer].

OBJECTIVE: To study the regulation of the mucin protein in colon cancer cell line HT-29 by recombinant human interleukin-6(rIL-6) and to further elucidate the development of colon cancer. METHODS: The HT-29 cells were treated with different concentrations of rIL-6(1, 2, 5, 10 and 20 µg/L), then flow cytometry and RT-PCR were used to detect the expression of mucin1 and mucin2. Transwell invasion assay was used to observe the effect of invasion capability of rIL-6 to HT-29 cells. RESULTS: In colon cancer, the expression of mucin 1 could be promoted by rIL-6 with concentration above 2 µg/L, the expression rates were(12.5±1.6)%, (26.6±2.7)%, (33.9±2.8)% and (58.9±2.5)%, respectively, higher than (8.0±0.8)% in the negative controls (P<0.01), meanwhile, the expression of mucin 2 decreased by rIL-6 with concentration above 2 µg/L, the expression rates were(30.5±2.6)%, (17.0±2.7)%, (11.0±2.0)% and (5.3±1.8)%, respectively, lower than (41.6±3.6)% in negative control(P<0.01). With the increase in rIL-6 concentration, the invasion of HT-29 cells was enhanced. CONCLUSIONS: In colon cancer, the expression of mucin1 can be promoted by rIL-6, while the expression of mucin2 can be inhibited. IL-6 is a promoting effect factor in colon cancer invasion and metastasis.

Mast cell degranulation induced by chlorogenic acid.

AIM: To investigate the mechanism of chlorogenic acid (CA)-induced anaphylactoid reactions. METHODS: Degranulation of peritoneal mast cells was assayed by using alcian blue staining in guinea pigs, and the degranulation index (DI) was calculated. CA-induced degranulation of RBL-2H3 cells was also observed and assayed using light microscopy, transmission electron microscopy, flow cytometry, and beta-hexosaminidase release. RESULTS: CA 0.2, 1.0, and 5.0 mmol/L was able to promote degranulation of peritoneal mast cells in guinea pigs in vitro, but it did not increase the degranulation of peritoneal mast cells in CA-sensitized guinea pigs compared with control (P>0.05). Treatment with CA 0.2, 1.0, and 5.0 mmol/L for 30, 60, and 120 min induced degranulation in RBL-2H3 cells in a dose- and time-dependent manner (P<0.01). Under transmission electron microscope typical characteristics of degranulation, including migration of granular vesicles toward the plasma membrane and integration combined with exocytosis, were observed, after CA or C48/80 treatment. Fluorescent microscopy and flow cytometric analysis showed that CA induced concentration-dependent translocation of phosphatidylserine in RBL-2H3 cells. beta-hexosaminidase release in RBL-2H3 cells was significantly increased after incubation with 1 mmol/L CA for 60 min and 5 mmol/L CA for 30 min (P<0.01). CONCLUSION: CA induces degranulation of peritoneal mast cells and RBL-2H3 cells in guinea pigs, which might be one of the mechanisms of the generation of anaphylactoid reactions induced by CA.