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.

Adipophilin: roles in physiology and pathology.

Adipophilin (ADRP/ADPH/PLIN2), an adipocyte differentiation-related protein, is highly expressed at a very early time during the differentiation of adipocytes. It assists in the formation and maintenance of intracellular lipid droplets and plays a role in regulating the physiological functions of the body. More and more studies indicate that it is involved in the occurrence and development of a variety of glycolipid metabolic diseases and tumours. In this review, we comprehensively stated the expression and functions of adipophilin and introduced its roles in physiology and pathology.

Secondary Tumors Arising from Nevus Sebaceus: A Multicenter Collaborative Study and Literature Review.

BACKGROUND: Although various benign and malignant tumors can arise in nevus sebaceus (NS), the demographic and clinicopathological features of the secondary tumors vary among different published reports. The aim of this study was to obtain a better understanding of the features of tumors secondary to NS. METHODS: A multicenter study was performed by reviewing patients diagnosed with NS from the Dermatology Department of the First Affiliated Hospital of Chongqing Medical University and Qijiang Hospital of the First Affiliated Hospital of Chongqing Medical University from 2010 to 2022. A literature review of case series of secondary tumors arising in NS was also conducted. RESULTS: We retrospectively analyzed the literature on tumors secondary to NS published since 2000, with a total of 443 cases, and carefully studied cases of tumors arising in NS from multiple centers since 2010, with a total of 54 cases. There were 497 cases in this study; 90.3% were benign tumors (n = 449), and the rest were malignant tumors (9.7%, n = 48). Syringocystadenoma papilliferum was the most common benign tumor, followed by trichoblastoma and trichilemmoma. Basal cell carcinoma was the most common secondary malignant tumor to NS, followed by squamous cell carcinoma. Two of these cases developed metastasis. Secondary malignancies developed at an earlier age in Caucasians than in Hispanics and Asians. CONCLUSION: The present study is the largest analysis of tumors secondary to NS. Racial differences were seen in secondary tumors to NS and may contribute to healthcare disparities between races.

Metastasis of a basosquamous carcinoma arising in a nevus sebaceus.

Nevus sebaceus (NS) is a congenital hamartoma of skin structures including the epidermis, sweat sebaceous glands, and hair follicles. It is known that secondary tumors can occur in NS. However, secondary metastatic malignancies are rare. Basosquamous carcinoma (BSC) is an aggressive type of basal cell carcinoma (BCC) characterized by squamous differentiation. Herein, we report a case of metastatic BSC that developed in a 73-year-old male with NS. The clinical presentation of this patient was that of an ulcerative nodule developing in a longstanding plaque-like lesion consistent with NS. Histopathological examination revealed characteristic features of BCC with some areas of squamous differentiation in addition to the structure of a typical NS. Immunohistochemical expression of Ber-EP4, AE1/AE3, and epithelial membrane antigen helped to make the diagnosis of BSC.

Expression of Hedgehog Signaling Pathway Proteins in Basal Cell Carcinoma: Clinicopathologic Study.

Objective: Basal cell carcinoma (BCC) is the most common type of cancer with a growing incidence rate over recent decades. The increasing economic burden and incidence of BCC have generated major interest in developing targeted therapies for this disease. The critical role of the Hedgehog (Hh) pathway in the pathogenesis of BCC has become evidently demonstrated. The purpose of this study was to observe the expression of PTCH1 and Gli1 in BCC and further evaluate their relationship with clinicopathological features. Methods: This retrospective study included 84 patients with BCC. Information of 84 patients with pathologically diagnosed BCC (including location, sex, tumor size, pathological type, and depth of invasion) were collected, and tissue paraffin blocks were collected for immunohistochemical staining. Western blot analysis for PTCH1 and Gli1 were also performed. The staining intensity and percentage of stained cells were expressed as a histochemical score (HSCORE). Results: PTCH1 and Gli1 were overexpressed in BCC compared with adjacent normal epidermis. Our study found that the expression of PTCH1 and Gli1 in BCC in exposed sites was significantly higher than in non-exposed sites. Moreover, no significant difference was observed in sex, Breslow thickness, tumor size or pathological type (P>0.05). Conclusion: PTCH1 and Gli1 were overexpressed in BCC. Higher PTCH1 and Gli1 expression were in exposed sites lesions. Our study suggests that UV radiation may be associated with aberrant activation of the Hh-PTCH1-Gli1 intercellular signaling pathway in BCC. The molecular mechanism of UV-related PTCH1 and Gli1 differential expression deserves more rigorous research in the future.

Targeting HIF-1α/NOTCH1 pathway eliminates CD44+ cancer stem-like cell phenotypes, malignancy, and resistance to therapy in head and neck squamous cell carcinoma.

Poor prognosis of head and neck squamous cell carcinomas (HNSCCs) results from resistance to chemotherapy and radiotherapy. To uncover the drivers of HNSCC resistance, including stemness and hypoxia, in this study, we compared the gene expression between CD44+ and CD44- HNSCC cells and assessed the correlation of CD44 and hypoxia-inducible factor 1α (HIF-1α) expression with mouse features and outcomes of patients with HNSCC. We combined the knockdown or activation of HIF-1α with in vitro and in vivo assays to evaluate effects on stemness and resistance of HNSCC cells. Analysis of clinical data showed that activation of HIF-1α in CD44+ patients with HNSCC was correlated with worse prognosis. Functional assays showed that HIF-1α promoted stemness, resistance, and epithelial-mesenchymal transition in HNSCC CD44+ cells. HIF-1α activated NOTCH1 signaling in HNSCC stem-like cells characterized by CD44 expression. Moreover, inhibition of these signaling proteins using shRNA or Evofosfamide (Evo) development for cancer treatment, reversed chemoresistance in vitro and in vivo. Taken together, our results indicated that targeting HIF-1α attenuated NOTCH1-induced stemness, which regulates responses to chemotherapy or radiotherapy and malignancy in CD44+ HNSCCs. HIF-1α/NOTCH1 signaling may represent a target for HNSCC treatment.

Adipophilin expression in skin lesions with clear cell histology.

AIMS: Clear cells formed due to depositions of glycogen or lipids in the cytoplasm commonly occur in various tissues. Adipophilin (ADP), a lipid regulatory protein, is closely related to lipid droplets. This study aims to examine adipophilin expression in clear cells of various skin lesions. METHODS: ADP expression was examined using immunohistochemistry in 108 sections from 15 skin lesion types with clear cell histology, namely, sebaceoma (n=16), sebaceous adenoma (n=3), sebaceous carcinoma (n=12), xanthomata cutis (n=10), xanthogranuloma (n=8), Paget's disease (n=10), Bowen disease (n=10), hidradenoma (n=9), atypical lipoma (n=5), superficial lipomatous nevus (n=5), metastatic renal cell carcinoma (n=5), squamous cell carcinoma (n=4), seborrheic keratosis (n=4), dermatofibroma (n=4) and clear cell sarcoma (n=3). RESULTS: ADP was not expressed in Bowen disease, hidradenoma or seborrheic keratosis. Four expression patterns, foamy, reticular, granular and punctate, were summarised based on their expression in clear cells. Different expression patterns were related to tissue origin and differentiation degree. Foamy expression was commonly observed in lesions with mature sebaceous glands and xanthomas; reticular expression in adipocytes; granular expression in xanthoma, xanthogranuloma and metastatic renal carcinoma and punctate expression in sebaceoma, sebaceous carcinoma, Paget's disease, squamous cell carcinoma and clear cell sarcoma. Furthermore, stronger staining with focal vesicular labelling was noted in sebaceoma than in sebaceous carcinoma. Characteristic labelling was noted, including the circular distribution in Touton giant cells of xanthogranulomas and focal distribution in the clear cells along the edge of necrotic tissue in clear cell sarcoma. CONCLUSIONS: ADP is useful in identifying intracytoplasmic lipids and can be used to diagnose skin lesions with clear cell histology, especially in some lesions with characteristic labelling.

HSP105 expression in cutaneous malignant melanoma: Correlation with clinicopathological characteristics.

BACKGROUND: Heat shock proteins can protect against stress-associated cellular challenges, but they can also protect some tumors from human immune system monitoring. Heat shock protein 105 (HSP105/110) is a high molecular weight protein whose expression has been reported in many cancers, but few studies on its role in cutaneous malignant melanoma have been published. In this study, we analyzed the relationship between HSP105 expression and the clinicopathological characteristics of CMM. METHODS: This retrospective study included 91 patients with CMM. The clinicopathological characteristics of CMM patients, including age, lesion duration, location, pathological classification, Clark's level, Breslow thickness, metastasis and recurrence, were collected. Immunohistochemical staining and Western blot analysis for HSP105 were performed. Pigmented nevi (n = 20) served as a control. The staining intensity and percentage of stained cells were expressed as a histochemical score (HSCORE). RESULTS: HSP105 was overexpressed in melanoma compared with nevi. Differences in the HSCORE between nevi (HSCORE = 1.05(0.15,1.50)) and CMM (HSCORE = 2.68(1.80,3.60)) were remarkable (P<0.001). Exposed site lesions, recurrent and metastatic lesions, nodular melanoma and lentigo maligna melanoma were closely associated with higher HSP105 expression (P = 0.011, P = 0.001 and P = 0.001, respectively). Moreover, no significant difference was observed in Clark's level, Breslow thickness, or lesion duration (P>0.05). CONCLUSION: HSP105 is overexpressed in CMM. Higher HSP105 expression in lesions is associated with different clinicopathological variables. HSP105 may be a potential target for the diagnosis, treatment and prognostic prediction of CMM.

Bullous Scabies: Clinical, Dermoscopic, and Pathologic Characteristics of Ten Patients.

Bullous scabies (BS) is a rare atypical clinical variant of scabies and is easily confused with bullous disorders. The diagnosis of BS is always a challenge, and physicians often misdiagnose BS patients. Patients with BS admitted from 2012 to 2020 were enrolled in this study. The clinical, dermoscopic, and pathological characteristics of the patients were analyzed retrospectively. Ten patients with BS were enrolled in this study. Seven of the 10 patients were male. The bullae were most commonly found on the thighs and arms (80% of patients). Only 30% of patients (3/10) tested positive for mites and/or eggs by the initial skin scraping, but 100% (5/5) of the patients who received dermoscopy tested positive. Among these 10 patients, only five received a skin biopsy. Subepidermal (4/5) and intraepidermal (1/5) bullae with eosinophil and neutrophil infiltration were observed in five patients. Direct immunofluorescence (DIF) indicated linear deposition of IgG in the basement membrane zone in three patients. Physicians should consider the possibility of BS in patients with blisters, pruritus, and poor response to corticosteroids. Dermoscopy should be prioritized for the differential diagnosis of BS to exclude other bullous disorders. Finally, a biopsy should be performed on each patient with bullae.

Expression of Heat Shock Protein 105 in Cutaneous Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics.

BACKGROUND: Heat shock proteins (HSPs), a group of heat stress proteins, are characterized by highly conserved properties. Malignant transformation is a cellular stress, and the expression of HSPs may be affected during this process. Heat shock protein 105 (HSP105) is a protective protein that has long been observed in many cancer types, but little attention has been given to cutaneous squamous cell carcinoma (CSCC). As such, the objectives of this study were to observe the expression of HSP105 on CSCC and evaluate its correlation with clinicopathological characteristics. METHODS: This retrospective study enrolled 60 patients with CSCC. The patients' clinical data, including sex, age, tumor location, tumor type, and degree of pathological differentiation, were collected. The expression of HSP105 was measured by Western blot and immunohistochemical staining. RESULTS: HSP105 expression was decreased in CSCC (HSCORE=0.65 (0.30, 1.98)) compared with normal skin (HSCORE=2.20 (1.50, 2.80)) (P<0.001). These results were consistent with the Western blot analysis. HSP105 immunostaining of Bowen disease (HSCORE=1.28 (1.08, 2.40)) revealed higher expression than in verrucous carcinoma (HSCORE=0.30 (0.23, 0.85)), keratoacanthoma (HSCORE=0.53 (0.29, 0.93)) and acantholytic squamous cell carcinoma (HSCORE=0.53 (0.41, 0.68) (P<0.01)). Poorly differentiated CSCC showed significantly higher expression of HSP105. CONCLUSION: Our study reveals for the first time that the expression of HSP105 is decreased in CSCC. We suggest that the molecular mechanisms underlying the differential expression of HSP deserve a more rigorous future study, the results of which might explain its role in carcinogenesis and its potential as a target for selective tumor therapy.

Diagnostic efficacy of anti-SARS-CoV-2 IgG/IgM test for COVID-19: A meta-analysis.

The serological testing of anti-SARS-CoV-2 immunoglobulin G (IgG) and/or IgM is widely used in the diagnosis of COVID-19. However, its diagnostic efficacy remains unclear. In this study, we searched for diagnostic studies from the Web of Science, PubMed, Embase, CNKI, and Wanfang databases to calculate the pooled diagnostic accuracy measures using bivariate random-effects model meta-analysis. As a result, 22 from a total of 1613 articles, including 2282 patients with SARS-CoV-2 and 1485 healthy persons or patients without SARS-CoV-2, were selected for a meta-analysis. Pooled sensitivity, specificity, and area under curve of the summary receiver operator curve (SROC) were: (a) 0.85 (95% confidence interval [CI]: 0.79-0.90), 0.99 (95% CI: 0.98-1.00), and 0.99 (95% CI: 0.97-0.99) for anti-SARS-CoV-2 IgG and (b) 0.74 (95% CI: 0.65-0.81), 0.99 (95% CI: 0.97-1.00), and 0.95 (95% CI: 0.93-0.97) for IgM. A subgroup analysis among detection methods indicated the sensitivity of IgG and IgM using enzyme-linked immunosorbent assay were slightly lower than those using gold immunochromatography assay (GICA) and chemiluminescence immunoassay (P > .05). These results showed that the detection of anti-SARS-CoV-2 IgG and IgM had high diagnostic efficiency to assist the diagnosis of SARS-CoV-2 infection. And, GICA might be used as the preferred method for its accuracy and simplicity.

Clinical significance of serum human epididymis protein 4 in liver fibrosis: An experimental study.

BACKGROUND: Human epididymis protein 4 (HE4) has been identified as marker for renal fibrosis. Present study aimed to investigate the clinical significance of serum HE4 in liver fibrosis. METHODS: Serum from 65 liver fibrosis patients, 68 hepatic patients without fibrosis, and 50 controls was collected respectively. Serum HE4 levels were measured by chemiluminescence immunoassay and compared among the groups. The relationships between serum HE4 levels and the clinical characteristics of liver fibrosis were also analyzed. A receiver operator characteristic curve was plotted to investigate the diagnostic efficacy of serum HE4 for liver fibrosis. Child-Pugh (C-P) score and liver fibrosis score were also evaluated. Data were analyzed by statistical software 13.0. RESULTS: Serum HE4 levels were significantly higher in liver fibrosis than that of controls [105.35 (82.64, 164.18) vs 46.2 (39.9, 58.9) pmol L, P = .00] and hepatic patients without liver fibrosis [105.35 (82.64, 164.18) vs 51.00 (44.02, 65.65) pmol L, P < .01]; Serum HE4 levels in liver fibrosis patients with C-P class C were significantly higher than those with C-P class A [143.75 (106.50, 186.08) vs 81.42 (69.73, 99.26) pmol L, P = .005] and C-P class B [143.75 (106.50, 186.08) vs 113.10 (88.92, 169.50) pmol L, P = .01]; the diagnostic sensitivity and specificity of serum HE4 levels for liver fibrosis detection were 87.5% and 81.1%, at a cutoff value of 69 pmol L; Serum HE4 levels in alcoholic liver fibrosis were higher than that of liver fibrosis with hepatitis B virus infection [131.30 (100.67, 228.35) vs 89.46 (73.74, 116.45) pmol L, P < .01]. CONCLUSION: Serum HE4 was closely correlated with C-P class and might be a potential marker for liver fibrosis.

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.

Laboratory findings of COVID-19: a systematic review and meta-analysis.

The Coronavirus Disease (COVID-19) pandemic first broke out in December 2019 in Wuhan, China, and has now spread worldwide. Laboratory findings have been only partially described in some observational studies. To date, more comprehensive systematic reviews of laboratory findings on COVID-19 are missing. We performed a systematic review with a meta-analysis to assess laboratory findings in patients with COVID-19. Observational studies from three databases were selected. We calculated pooled proportions and 95% confidence interval (95% CI) using the random-effects model meta-analysis. A total of 1106 articles were identified from PubMed, Web of Science, CNKI (China), and other sources. After screening, 28 and 7 studies were selected for a systematic review and a meta-analysis, respectively. Of the 4,663 patients included, the most prevalent laboratory finding was increased C-reactive protein (CRP; 73.6%, 95% CI 65.0-81.3%), followed by decreased albumin (62.9%, 95% CI 28.3-91.2%), increased erythrocyte sedimentation rate (61.2%, 95% CI 41.3-81.0%), decreased eosinophils (58.4%, 95% CI 46.5-69.8%), increased interleukin-6 (53.1%, 95% CI 36.0-70.0%), lymphopenia (47.9%, 95% CI 41.6-54.9%), and increased lactate dehydrogenase (LDH; 46.2%, 95% CI 37.9-54.7%). A meta-analysis of seven studies with 1905 patients showed that increased CRP (OR 3.0, 95% CI: 2.1-4.4), lymphopenia (OR 4.5, 95% CI: 3.3-6.0), and increased LDH (OR 6.7, 95% CI: 2.4-18.9) were significantly associated with severity. These results demonstrated that more attention is warranted when interpreting laboratory findings in patients with COVID-19. Patients with elevated CRP levels, lymphopenia, or elevated LDH require proper management and, if necessary, transfer to the intensive care unit.

Diagnostic Accuracy of Dermoscopy for Scabies.

The diagnostic accuracy of dermoscopy (DS) for scabies, a highly contagious parasitic disease, remains disputed. This study aimed to assess the diagnostic accuracy of DS in scabies, analyze the factors influencing DS, and explore its role in post-treatment evaluation. Patients with suspected scabies were randomly divided into 2 groups: 71 patients in the skin scraping (SS) group and 73 patients in the DS group. The diagnostic efficiencies of SS and DS in these groups were calculated. We also analyzed the influence of body part and investigator competence on the accuracy of DS. Then 16 body parts with typical signs of scabies were monitored by DS 2 and 4 day after sulfur ointment treatment. The sensitivity and specificity of DS were 98.3% and 88.5%, respectively. Hands, arms, and the abdomen had higher positivity rates than other body parts (P<0.001). The accuracy of dermatologists' interpretations of images negative for scabies in the intermediate- and high-level groups was higher than that in the low-level group (P<0.001). At follow-up, the mites were still visible on 43.8% to 62.5% of the skin lesions 2 and 4 day after sulfur ointment treatment. These results showed that DS could significantly increase the accuracy of diagnosing scabies owing to its high sensitivity and specificity. Therefore, it may be useful for monitoring clinical responses to anti-parasitic treatment.