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Objective:To analyze clinical and histopathological features of cutaneous horns, and to explore their relationship.Methods:A total of 204 patients with cutaneous horns confirmed by clinical and histopathological examinations were collected from Department of Pathology, Shanghai Skin Disease Hospital between January 2014 and May 2020, and their clinical and histopathological data were retrospectively analyzed.Results:Among 204 patients, there were 88 males and 116 females with the age being 70.47±14.76 years and median ( P25, P75) course being 6 (6, 24) months. Cutaneous horns were solitary in 201 cases, and multiple in 3. There were a total of 207 cutaneous horns, including 163 (78.74%) located on the head, face and neck, 18 (8.70%) on the trunk and 26 (12.56%) on the extremities. According to histopathological conditions at the base of the cutaneous horns, 154 (74.40%) cutaneous horns were considered to arise from benign lesions (named as benign horns) , including viral warts ( n=129) , seborrheic keratosis ( n=15) , inverted follicular keratosis ( n=3) , trichilemmomas ( n=5) , pyogenic granuloma ( n=1) and calcifying epithelioma ( n=1) ; 40 (19.32%) were considered to arise from premalignant lesions (actinic keratosis) and named as premalignant horns; 13 (6.28%) were considered to arise from malignant lesions (named as malignant horns) , including Bowen′s disease ( n=5) and squamous cell carcinoma ( n=8) . The average ages of patients with premalignant and malignant horns were significantly higher than those of patients with benign horns ( H=4.05, 3.16, respectively, both P < 0.01) . The base width of the malignant horns was significantly higher than that of the premalignant and benign horns ( H=2.74, 3.49, P < 0.05, 0.01, respectively) , and there was no significant difference between the premalignant and benign horns ( H=0.73, P > 0.05) . The height to base width ratio was significantly lower in the premalignant and malignant horns than in the benign horns ( H=4.06, 3.72, respectively, both P < 0.01) . The incidence rate of basal erythema was significantly higher in the premalignant and malignant horns than that in the benign horns ( χ2=29.57, 6.23, P < 0.01, 0.05, respectively) , and bleeding and crusting occurred more frequently in the malignant horns compared with the benign horns ( χ2=4.89, P < 0.05) . Conclusions:The base of most cutaneous horns is benign, which mainly includes viral warts, and premalignant and malignant horns account for about a quarter. Male, older age, wide base, low ratio of the height to base width, basal erythema, history of bleeding and crusting can serve as clues to early recognition of malignant lesions at the base of cutaneous horns.
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Objective To analyze histopathological and clinical features of dermatofibroma,and to explore the relationship between them.Methods Clinical and histopathological data were collected from 150 patients with histopathologically confirmed dermatofibroma in Department of Pathology,Shanghai Skin Disease Hospital from September 2017 to August 2018,and analyzed retrospectively.Results Among the 150 patients,65 were males,and 85 were females.Their age was 42 ± 13.8 years,and the course of disease ranged from 3 months to 30 years.Some of the patients had concomitant symptoms,mainly manifesting as itching,some had spontaneous pain and mild tenderness,and 18 patients had a history of injury,insect bite or infection at lesion sites.Skin lesions mainly occurred on the extremities (107 cases,71.3％),and most were solitary (105 cases,70％).Before pathological examinations,102 cases were clinically diagnosed as dermatofibroma,16 as epidermoid cyst,13 as pigmented nevus,3 as keloid,12 as skin mass,1 as malignant melanoma,1 as xanthogranuloma,1 as prurigo nodularis,and 1 as neurofibroma.Among 169 hematoxylin and eosin (HE)-stained sections,25 (14.8％) appeared to be consistent with aneurysmal dermatofibroma,66 (39.1％)with cellular dermatofibroma,36 (21.3％) with sclerosing dermatofibroma,and 22 (13.0％)with epithelioid dermatofibroma.Coexistence of two or more subtypes could be seen in 12 sections.There were also a few new variants,such as dermatofibroma with hyperplastic sweat duct (1 case),deep dermatofibroma (3 cases),dermatofibroma with epithelioid cells intermingled with hyperplastic collagen (1 case).The duration of aneurysmal dermatofibroma varied from 7 months to 30 years,and most manifested as skin masses on the lower extremities.A relatively short course of disease was observed in patients with cellular dermatofibroma,who often visited a hospital several months after the onset,and cellular dermatofibroma was commonly observed on the extremities and frequently accompanied with itching and pain.The duration of sclerosing or atrophic dermatofibroma was usually long for years or decades,and it commonly occurred on the upper limbs without concomitant symptoms.Epithelioid dermatofibroma of varied durations had various clinical manifestations,frequently occurred on the lower limbs without concomitant symptoms.Conclusions The clinical and pathological manifestations of dermatofibroma are diverse.Different dermatofibroma lesions can share similar typical histopathological manifestations,and atypical pathological features can interfere with the diagnosis of dermatofibroma.
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Objective To investigate clinical manifestations and histopathological features of cutaneous metastasis of malignant visceral tumors,to improve diagnosis of cutaneous metastasis of malignant visceral tumors.Methods A total of 50 patients with cutaneous metastasis of malignant visceral tumors were enrolled from Shanghai Skin Disease Hospital between January 2012 and June 2018,and the features of the skin lesions,source of tumors,histological and immunohistochemical features were retrospectively analyzed.Results There were 24 males and 26 females among the 50 patients,with an average age of 67.0 years (range,28-93 years).The average duration from the notice of cutaneous metastasis of malignant visceral tumors to the first clinic visit was 4.4 months (range,2 weeks-13 months).Cutaneous metastasis of malignant visceral tumors mostly occurred on the chest (16 cases),followed by the lower limbs (7 cases),the head and neck (5 cases),the back (5 cases),the abdomen (4 cases),the external genitalia (4 cases) and the upper limbs (3 cases).Cutaneous metastasis of malignant visceral tumors simultaneously or successively occurred on multiple sites in 6 cases.The most common skin lesion was solitary lump (35 cases,70％),followed by multiple papules and nodules (13 cases,26％),infiltrative plaques (1 case,2％) and non-infiltrative erythema (1 case,2％).The most common types of primary cancers were breast cancer (11 cases,22％),lung cancer (9 cases,18％) and gastric cancer (6 cases,12％),and the most common histological types were adenocarcinoma (32 cases,64％) and squamous cell carcinoma (8 cases,16％).Conclusions Cutaneous metastasis of malignant visceral tumors mostly occur in the elderly and on the chest.The most common skin lesion was solitary lump.Breast carcinoma,lung cancer and gastric cancer are the most common primary tumors,and adenocarcinoma and squamous cell carcinoma are the most common histological types.
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Objective To investigate the association of tumor necrosis factor-ot (TNF-α) gene promoter polymorphisms with generalized pustular psoriasis.Methods Totally,91 patients of Han nationality with generalized pustular psoriasis (generalized pustular psoriasis group) and 102 health checkup examinees (healthy control group) were enrolled into this study.PCR and direct sequencing were performed to analyze the-238,-308 and-857 polymorphic sites of the TNF-α promoter.Results The frequency of the A allele at TNF-α-238 site was significantly higher in the generalized pustular psoriasis group than in the healthy control group (P =0.003,OR =4.819,95％ CI:1.581-14.694),so was the frequency of GA/AA genotype (P =0.006,OR =4.455,95％ CI:1.410-14.077).However,no significant differences were observed in the frequencies of G/A alleles (P =0.794) and GG/GA/AA genotypes (P =0.786) at TNF-o-308 site,or in the frequencies of C/T alleles (P =0.474) and CC/CT/TT genotypes (P =0.453) at TNF-α-857 site,between the generalized pustular psoriasis group and healthy control group.Conclusion TNF-α-238G ＞ A polymorphisms may be associated with the occur-rence of generalized pustular psoriasis.
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ObjectiveTo study the relationship between fasting plasma glucose (FPG) level and the first cerebral infarction event in the population with diabetes.Methods This was a prospective cohort stndy.8 306 diabetic subjects who determined FPG ≥ 7.0 mmol/L or treated with insulin or hypoglycemic drugs and FPG ＜7.0 mmool/L as the observation population and were followed-up for (48.01 ± 3.14) months.During the course,cerebral infarction events were determined every 6 months.Results( 1 ) By the end of following-up,with the increasing levels of the baseline FPG,the total cholesterol (TC),triglyceride (TG) levels were gradually increased in the diabetic population,the differences were significant [ TC:( 4.93 ± 1.15,5.10 ± 1.20,5.15 ± 1.28,5.33 ± 1.35 ) mmol/L,TG:( 1.70 ± 1.26,1.83 ± 1.29,2.18 ± 1.76,2.41 ± 2.08 ) mmol/L,P＜0.05 ] ; the plasma low density lipoprotein-cholesterol (LDL-C),systolic blood pressure ( SBP),diastolic blood pressure ( DBP),and body mass index (BMI) levels were also increased significantly ( P＜0.05 ).(2) The ineidence of cerebral infarction event in the group of patients with 7.0 mnol/L ≤ FPG ＜ 9.0 mmol/L was the lowest,the differences were significant ( 2.1％,P ＜0.01 ).Compared with the group of 7.0 mmol/L≤ FPG＜9.0 mmol/L,after adjusting for age,sex,BMI,SBP,DBP,TC,TG,low density lipoprotein-cholesterol,high density lipoprotein-cholesterol,smoking,diabetic duration and treatment,the relative risk for cerebral infarction events were 1.85 (95％ CI 1.09-3.15,P＜0.05) and 1.54 (95％CI 1.16-2.05,P ＜ 0.01 ) for those groups with 6.1 mmol/L ≤ FPG ＜ 7.0 mmol/L and FPG ≥ 9.0 mmol/L respectively.ConclusionThe risk of new in cidence of cerebral infarction events seems to be the lowest in the group of diabetic patients whose FPGs are wihin 7.0-9.0 mmol/L range.
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Objective To study the expression of cellular FLICE inhibitory proteins(c-FLIP)in peripheral blood B lymphocytes in patients with systemic lupus erythematosus (SLE)and its correlation with clinical features.Methods Blood samples were obtained from 53 patients with SLE and 30 normal human controls.Flow cytometry and ELISA were performed to measure the expression of c-FLIP in pefipheral blood B lymphocytes and serum levels of IL-4 and IL-10,respectively.Relevant laboratory examinations were carried out for these patients.SLE disease activity index(SLEDAI)score was calculated for patients.Results The positivity rate of c-FLIP in B lymphocytes was 3.11%±0.70%in 18 patients with active SLE.significantly higher than that in 35 patients with inactive SLE (0.78%±0.28%)and normaI controls(0.68%±0.12%),while no statistical difierence was found between inactive patients and controls(t=1.56,P＞0.05).In SLE patients,the expression of c-FLIP showed a positive correlation with SLEDAl score(r=0.96.P＜0.05),erythrocyte sedimentation rate(r=0.96,P＜0.01),serum level of C reactive protein(r=0.92.P＜0.01)and the titer of antinuclear antibodies(r=0.86,P＜0.01),whereas in 36 patients with leucopenia.a negative correlation was noticed between white blood cell count and the expression level of c-FLIP(r=-0.94,P＜0.0 1).The 23 patients with lupus nephritis had a higher level of c-FLIP than those without lupus nephritis(3.04%±1.09%vs 1.76%±1.09%,t=4.23,P＜0.05).Additionally.the expression of c-FLIP positively correlated with the serum level of IL-4 and IL-10(r=0.80,0.89.respectively,both P＜0.01).Conclusions In patients with active SLE,the expression of c-FLIP is upregulated in peripheral blood B lymphocytes,and positively correlated with the severity of SLE as well as the serum level of IL-4 and IL-10.The upregulation of c-FLIP in B cells might play a certain role in deficient apoptosis or clearance of activated B cells in SLE.
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Objective To investigate the effects ofendothelin-1 (ET-1) and endothelin-3 (ET-3) on the expression of transformation growth factor-beta 1 (TGF-β1) and phosphorylation of Smad 3 in malignant melanoma cell line, A375. Methods Cultured A375 cells were classified into 5 groups, i.e. control group (no stimulation), ET-1 group (stimulated with ET-1), ET-1+BQ123 group (treated with ET-1 and BQ123),ET-1 + BQ788 group (treated with ET-1 and BQ788), ET-3 group (stimulated with ET-3), to receive different stimulation. The working concentrations were 0, 0.1, 1, 10, 100 nmol/L for ET-1 and ET-3, 10 μmol/L for BQ123 and BQ788. After another 12- and 24-hour culture, ELISA, RT-PCR and Western blot were used to detect the expression of TGF-β1 protein and mRNA as well as phosphorylated Smad 3 (P-Smad 3). Results The expression of TGF-β1 in A375 cells was up-regulated by ET-1, but down-regulated by ET-3, and both of the effects were in a concentration-dependent manner. Under the stimulation with ET-1 and ET-3 of 100 nmol/L, the level of TGF-β1 reached 1289.38 ± 89.42 ng/L per 105 cells and 85.09 ± 9.37 ng/L per 105 cells, respectively, significantly different from that in unstimulated cells (both P < 0.05). BQ123 signifi-cantly blocked the up-regnlatory effect of ET-1 on the expression TGF-β1 protein(P < 0.05), but BQ788 had no significant influence on the effect, so was the case with TGF-β1 mRNA. Western blot revealed that ET-1significantly elevated the expression of P-Smad 3 in A375 cells (P <0.05), and the elevation was significantly inhibited by BQ123, but not by BQ788. The expression of P-Smad 3 was statistically decreased by ET-3 in A375 cells (P <0.05). Conclusions The expression of TGF-β1 could be enhanced by ET-1, but suppressed by ET-3. It is likely that endothelin receptor A mediates the phosphorylation of Smad 3 induced by ET-1.
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Objective To construct an eukaryotic expression vector for TAP genes fused with enhanced green fluorescent protein(EGFP)gene,and to analyze the expression and subcellular localization of the fusion protein in A375 human malignant melanoma cells transfected with the eukaryotic expression vector.Methods A375 cells were cotransfected with the combination of plasmid(P)TAP1-EGFP or pTAP2-EGFP and pDsRed2-endoplasmic reticulum(ER),or with pEGFP-TAP1 and-TAP2,or monotransfected with pTAP1-EGFP or pTAP2-EGFP alone.The monoclonal A375 cells stably expressing TAP were obtained by G418 selection.Then.the distribution and expression of fusion proteins were assessed in A375 cells by using fluorescence microscopy and Western blot,respectively.Flow cytometry was used to measure the expression of HLA class Ⅰ on A375 cells.Results Transfection of A375 cells with pTAP1-EGFP or pTAP1-EGFP and pTAP2-EGFP significantly increased the expression of TAP 1 and TAP 2 in as well as HLA class Ⅰ antigen on A375 cells.The green fluorescence of TAP1-EGFP and TAP2-EGFP overlapped with the red fluorescence of ER marker in cotransfected cells.indicating that TAP was localized subcellularly on the ER.Conclusions The expression vector for TAP-EGFP fusion gene has been constructed cuccessfully and expressed in A375 cells,and the expressed fusion protein is subcelluiarly localized to ER.This study will provide a basis for the research into subsequent immune response following induction of TAP expression.
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Objective To investigate the expression of glucose transporter type 1(GLUT-1)and hypoxia-inducible factor 1 (HIF-1)α in psoriatic lesions,and to explore their correlations with keratinocyte proliferation.Methods Biopsy specimens were obtained from 30 patients with psoriasis and 20 normal human controls.Immunohistochemistry and Western blotting were used to examine the protein expression of GLUT-1 and HIF-1α in these specimens.Results GLUT-1 and HIF-1α were mainly expressed in the basal layer of the control skin,but throughout the whole epidermis of psoriatic lesions.A significant increase was observed in the expression of GLUT-1 and HIF-1α in psoriatic lesions compared with that in the control skin (botb P＜0.01).In the case of psoriatic lesions,both the expression of GLUT-1 and HIF-1α was positively correlated with that of Ki-67(r=0.70,0.81 respectively,both P＜0.01),and positive correlation was also found between the expression of GLUT-1 and HIF-1α(r=0.85.P＜0.01).Conclusion Our data suggest that uprcgulation Of GLUT-1 and HIF-1α expression in psoriatic lesions might contribute to the proliferation of keratinocytes and psoriasis development.
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Objective To investigate the expression and distribution of cellular FLICE-inhibitory protein (c-FLIP) in peripheral blood and lesions of psoriatic patients. Methods Peripheral blood and skin samples were obtained from 30 patients with psoriasis vulgaris and 20 normal controls. Flow cytometry was used to detect intracellular c-FLIP protein in peripheral T and B lymphocytes, immunohistochemistry to examine the expression of c-FLIP in lesional tissue. Results Based on the positivity rate of c-FLIP, there was a significant increase in T lymphocytes in active psoriasis compared with regressive psoriasis and normal controls (6.32%±1.17% vs 2.64%±0.74% and 2.28%±0.54%, P＜0.01 and 0.05, respectively), while no significant difference was found in B lymphocytes among these three groups (0.78%±0.16%, 0.71%±0.32%, 0.69%±0.18%, respectively, P＞0.05). The expression intensity of c-FLIP in keratinocytes was also higher in active psoriasis than in regressive psoriasis and normal controls (89.73±5.24 vs 117.40±7.50,121.58±7.93, P＜0.01 and 0.05 respectively), and there was no difference between regressive psoriasis and normal controls (P＞0.05). Conclusions c-FLIP is highly expressed in lesions and peripheral T lymphocytes of patients with active psoriasis, suggesting the possible involvement of c-FLIP in the proliferation of T lymphocytes in psoriasis.
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Objective To explore the expression of transporter associated with antigen processing (TAP) and major histocompatibility complex class (MHC)-Ⅰ molecule in malignant melanoma cell lines. Methods Three malignant melanoma cell lines, including A375, A875, and KZ28 cells as well as normal melanocytes were cultured. Western blot, reverse transcription PCR and flow cytometry were used to detect the protein and mRNA expression of TAP as well as the membrane expression of MHC-Ⅰ in these cells. Results A significant decrease was observed in the expression of TAP mRNA (t = 5.89, 4.45 and 4.57 re-spectively, all P< 0.01) and protein (t= 5.46, 4.32 and 4.67 respectively, all P< 0.01) in A375, A875 and KZ28 cells compared with the melanocytes, with the strongest decrease occurring in A375 cells. Similarly, the expression of MHC-Ⅰ molecule was significantly lower in A375, A875 and KZ28 cells than that in the melanocytes (t= 6.16, 5.22 and 5.61 respectively, all P< 0.01).Conclusions The protein and mRNA expres-sion of TAP is down-regulated in three melanoma cell lines A375, A875 and AZ28, which may contribute to the escape of melanoma cells from human immune surveillance.
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In order to investigate the expression of endothelin receptor B (ETR-B) in human ma-lignant melanoma (MM) cells A375 and SK-mel-1 and the proliferative effects of endothelin 3 (ET3) on A375 cells, RT-PCR was applied to detect the expression of ETR-B gene in human MM cells A375 and SK-mel-1. MTT method was used to evaluate the growth enhancing effects of ET3 on A375 cell line in vitro. The results showed that ETR-B gene was expressed in both MM A375 and SK-mel-1 cells. ET3 had stronger ability to enhance the proliferation of A375 cells in vitro in a con- centration-dependent manner. It was suggested that ET3/ETR-B might play an important proliferative role in MM.
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In order to investigate the expression of endothelin receptor B (ETR-B) in human malignant melanoma (MM) cells A375 and SK-mel-1 and the proliferative effects of endothelin 3 (ET3) on A375 cells, RT-PCR was applied to detect the expression of ETR-B gene in human MM cells A375 and SK-mel-1. MTT method was used to evaluate the growth enhancing effects of ET3 on A375 cell line in vitro. The results showed that ETR-B gene was expressed in both MM A375 and SK-mel-1 cells. ET3 had stronger ability to enhance the proliferation of A375 cells in vitro in a concentration-dependent manner. It was suggested that ET3/ETR-B might play an important proliferative role in MM.