Neutrophil extracellular traps promote macrophage inflammation in psoriasis.

Psoriasis is a chronic inflammatory skin disease connected with immune dysregulation. Macrophages are key inflammatory cells in psoriasis but the specific mechanism of their activation is not fully understood. Neutrophil extracellular traps (NETs) have been shown to regulate macrophage function. Here, we found that NET deposition was increased in psoriasis lesions. Peptidylarginine deaminase 4 (PAD4, a key enzyme for NET formation) deficiency attenuated skin lesions and inflammation in an imiquimod-induced psoriatic mouse model. Furthermore, the STING signaling pathway was markedly activated in psoriasis and abolished by PAD4 deficiency. PAD4-deficient mice treated with the STING agonist DMXAA exhibited more severe symptoms and inflammation than control mice. Mechanistically, the STING inhibitor C-176 inhibited NET-induced macrophage inflammation and further inhibited the proliferation of HaCaT cells. Our findings suggest an important role of NETs in the pathogenesis of psoriasis, and activation of macrophage STING/NF-κB signaling pathway might involve in NETs related psoriasis.

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.

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.

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.

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.

Progranulin Promotes Bleomycin-Induced Skin Sclerosis by Enhancing Transforming Growth Factor-ß/Smad3 Signaling through Up-Regulation of Transforming Growth Factor-ß Type I Receptor.

Progranulin (PGRN) is an autocrine growth factor with numerous physiological and pathologic roles. Previous reports demonstrated PGRN could increase dermal fibroblasts in wound healing and activate cancer-associated fibroblasts in some cancers. Because systemic sclerosis (SSc) is a prototypical fibrosis-related disorder, here, the aim was to clarify the role and mechanism of PGRN in bleomycin (BLM)-induced model of SSc for the first time. It was observed that the serum PGRN levels were increased in SSc patients compared with healthy controls. Immunohistology and quantitative RT-PCR demonstrated that PGRN was also elevated in the lesion from the mice model of BLM-induced dermal fibrosis. In addition, in BLM-treated mice, PGRN deficiency not only attenuated dermal fibrosis but also decreased the differentiation of myofibroblasts. The reduced progression of skin sclerosis in PGRN-deficient mice was associated with down-regulation of transforming growth factor (TGF)-ß receptor I (TßR I) and decreased level of phosphorylated Smad3, with correspondingly impaired expression of its downstream target gene connective tissue growth factor (CTGF) in skin lesion. In contrast, exogenous PGRN significantly increased the level of TßR I and phosphorylated Smad3 in cultured mouse fibroblasts. This study demonstrates that PGRN plays a promoting role in the development of dermal fibrosis through the activation of the TGF-ß/Smad3 signaling via up-regulation of TßR I. PGRN may be a new therapeutic target in SSc.

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.

Quantification of serum HBXAP DNA in lung cancer patients by quantitative fluorescent polymerase chain reaction.

Hepatitis B virus x associated protein (HBXAP), as a subunit of chromatin remodeling and spacing factor, plays a critical role in cancer development through gene amplification. In this study, we aimed to quantify the levels of serum HBXAP DNA, to analyze and compare its diagnostic value with existing clinical parameters in lung cancer, and to potentially provide a novel tumor marker for lung cancer. Serum HBXAP DNA from 65 lung cancer patients and 20 healthy controls was quantified using real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) analysis. The data were analyzed by statistical software SPSS 13.0. We found that serum HBXAP DNA levels in lung cancer patients were higher compared to healthy controls (u = 219.0, p = 0.001) and were closely associated with TNM stage and lymph node metastasis (p = 0.015 and p = 0.016, respectively). However, serum HBXAP DNA levels were not associated with patient age, gender, smoking status, histological type, or tumor size (p > 0.05). We identified a sensitivity of 61.9 % and a specificity of 93.7 % for the ability of HBXAP DNA levels to detect lung cancer at a cutoff value of 1,557.6 copies/µl. The sensitivity for existing lung-tumor markers, such as squamous cell carcinoma antigen, cytokeratin fragment 21-1, and neuron specific enolase, was increased from 35.7 %, 53.5 %, and 56.0 % to 75.0 %, 86.0 %, and 80.0 %, respectively, by inclusion of serum HBXAP DNA. Taken together, quantification of serum HBXAP DNA by FQ-PCR could potentially serve as a novel complementary tool for the clinical screening and detection of lung cancer.

Significance of CAVI, hs-CRP and homocysteine in subclinical arteriosclerosis among a healthy population in China.

PURPOSE: The purpose of this study is to evaluate the ability of cardio-ankle vascular index (CAVI), high-sensitivity C-reactive protein (hs-CRP) levels and homocysteine (Hcy) levels to screen for subclinical arteriosclerosis (subAs) in an apparently healthy population, with the view to obtaining an optimal diagnostic marker or profile for subAs. METHODS: Subjects (152) undergoing routine health examinations were recruited and divided into two groups: carotid arteriosclerosis (CA) and non-carotid arteriosclerosis (NCA), according to carotid intima-media thickness (CMIT). CAVI was calculated based on blood pressure and pulse wave velocity. Serum hs-CRP and Hcy levels were also measured. A Receiver Operating Characteristic (ROC) curve was plotted to evaluate the efficacy of each in carotid arteriosclerosis screening. Ten parameter combinations, designated W1 to W10, were compared in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: The levels of all three parameters were significantly higher in the CA group, compared with the NCA group. ROC curves showed that the area under the curve (AUC) for CAVI was 0.708 (95%CI: 0.615-0.800), which is significantly larger than that of either hs-CRP (0.622) or Hcy (0.630), respectively (P < 0.001). Maximum sensitivity (100%) and NPV (100%) were attained with W10, while maximum specificity (86.2%) and PPV (46.7%) were obtained with W7. With W9, the maximum Youden index (0.416) was obtained, with a sensitivity of 77.8% and specificity of 63.8%. CONCLUSIONS: CAVI is more effective than hs-CRP or Hcy for subAs screening. The optimal profile was obtained with a combination of CAVI and other parameters.

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.

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.

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.

Retrospective analysis of the predictive effect of coagulogram on the prognosis of intracerebral hemorrhage.

OBJECTIVE: To determine the effective index of coagulogram after acute intracerebral hemorrhage (ICH) for predicting the outcome of ICH. METHODS: A total of 641 patients with ICH were divided into two groups: the effective treatment group (healing well and improving) and ineffective treatment group (non-improving and dying). The coagulogram results of the two groups were analyzed with SPSS software 13.0, including PT, APTT, TT, and Fbg. The differences in these parameters were found by independent samples T test and Kruskal-Wallis test between the two groups. Then, the different parameters were obtained by logistic regression, which were significantly associated with the prognosis of acute cerebral hemorrhage patients. In addition, the odds ratio for the special indicators was calculated by chi-square test. RESULTS: Only PT had a significant difference between the groups (p<0.05) among the four parameters. The binary logistic regression analysis indicated that PT (p=0.003) and APTT (p=0.043) were related to the outcome of ICH patients. According to the chi-square test, the OR (odds ratio) of prolonged PT is 2.40 (1.34-4.29 with 95% CI) and that of prolonged APTT is 1.57 (1.01-2.42 with 95% CI). CONCLUSION: Prolonged PT and APTT are risk factors affecting the prognosis of ICH patients. Monitoring and controlling PT and APTT are advisable for improving the prognosis of ICH patients.

Retrospective analysis of the predictive effect of routine biochemical results on the prognosis of intracerebral hemorrhage.

OBJECTIVE: To find the effective biochemical factors for predicting the outcome of acute intracerebral hemorrhage (ICH). METHODS: According to the outcome, 497 ICH patients were divided into two groups (effective treatment group, ineffective treatment group). The routine biochemical results were analyzed between groups with SPSS software 13.0, including TC, TG, HDL-c, LDL-c, UA, and Glu. The differences of these items were found by independent sample T test and Kruskal-Wallis test between groups. Then the items, which were significantly associated with the prognosis of ICH patients, were obtained by the logistic regression. In addition, we calculated the odds ratio (OR) for the special indicators by chi-square test. RESULTS: Only UA, Glu, and HDL-c had significant differences between groups (P<0.05) among the six biochemical items. The binary logistic regression analysis indicated that high Glu and UA were related to the outcome of ICH (P<0.01). By chi-square test, the OR of high Glu was 3.95 (2.27-6.87 with 95% CI) and that of high UA was 2.19 (1.16-4.11 with 95% CI), but HDL-c's OR was only 0.90 (0.41-1.98 with 95% CI) without statistical significance. CONCLUSION: High Glu and UA were risk factors for the prognosis of ICH; monitoring and controlling the Glu and UA may be advisable improving the prognosis of ICH.