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Objective:To investigate clinical characteristics of bullous pemphigoid (BP) developing after the treatment with dipeptidyl peptidase-Ⅳ inhibitors (DPP4i) in patients with diabetes mellitus.Methods:A total of 116 inpatients with BP complicated by diabetes mellitus were collected from the Seventh People′s Hospital of Shenyang between January 2014 and December 2020, and divided into 2 groups: DPP4i-BP group treated with DPP4i before the onset of BP, and general BP group receiving no treatment with DPP4i. General clinical data, skin lesion area, laboratory indicators, treatment regimens, and prognosis were analyzed and compared between the above 2 groups, the time interval from the administration of DPP4i to the diagnosis of BP was recorded in the DPP4i-BP group. One-way analysis of variance was used to compare measurement data among multiple groups, two-independent-sample t test was used for comparisons between two groups, and paired t-test for intra-group comparisons before and after treatment; chi-square test was used to compare enumeration data between groups. Results:There were 32 patients aged 77.17 ± 15.32 years in the DPP4i-BP group, with a male-to-female ratio being 15∶17; there were 84 patients aged 76.65 ± 19.32 years in the general BP group, with a male-to-female ratio being 43∶41. The time interval from the administration of DPP4i to the diagnosis of BP was 14.61 ± 3.93 months in the DPP4i-BP group. The time interval for vildagliptin was the shortest (5.42 ± 2.84 months) , and there was a significant difference in the time interval among vildagliptin, sitagliptin, linagliptin and saxagliptin ( F= 8.93, P < 0.001) . The proportion of patients with severe BP was significantly higher in the DPP4i-BP group (16 cases, 50%) than in the general BP group (25 cases, 29.76%; Z= 2.63, P= 0.008) . There was no significant difference in the positivity rate of anti-BP180 antibody between the two groups ( χ2= 0.03, P= 0.870) . However, the level of anti-BP180 antibody was significantly higher in the DPP4i-BP group than in the general BP group before and after treatment ( P= 0.015, < 0.001, respectively) , and the decrease in the level of anti-BP180 antibody was significantly less in the DPP4i-BP group than in the general BP group after treatment ( t= 5.11, P < 0.001) . There was no significant difference in the average effective dose of glucocorticoids required to control the disease between the two groups ( t= 1.00, P= 0.322) . However, the DPP4i-BP group showed a significant increase in the average time required to control the disease and in the proportion of patients requiring combined treatment with immunosuppressants or other drugs compared with the general BP group ( t= 6.72, 10.05, P < 0.001,= 0.002, respectively) . Within 6 months after the start of systemic treatment, the recurrence rate was significantly higher in the general BP group (17 cases, 27.86%) than in the DPP4i-BP group (2 cases, 7.69%; χ2= 4.35, P= 0.037) ; at 6 months, the average dose of glucocorticoids was also significantly higher in the general BP group than in the DPP4i-BP group ( t= 7.04, P < 0.001) . Conclusions:Among the DPP4i hypoglycemic drugs, vildagliptin was the most common drug administrated by patients before the onset of BP, with the shortest interval from the administration to the onset of BP. DPP4i-BP may be difficult to control at the early stage, but the prognosis is good.
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ObjectiveTo analyze the distribution and density of Langerhans cells and dermal CD68 positive histiocytes in lesions of secondary keloid.MethodsTissue specimens were resected from the lesions of 30 patients with secondary keloid and normal skin of 14 human controls.Immunohistochemistry was performed to observe the expressions of CD68 and CD1a in these specimens.A micrometer was used to count the number of positively stained cells per unit area.The Student's t test was conducted for data analysis by using the SPSS software.ResultsThe density of CD1a+ Langerhans cells was (61 ± 49) cells/mm2 in the epidermis of secondary keloid lesions, (258 ± 61 ) cells/mm2 in the control epidermis,and(40 ± 65) cells/mm2 in the dermis of keloid lesions.CD68+ cells were absent in the epidermis of keloid lesions.Significant differences were observed in the density of CD1a+ Langerhans cells between the lesional and normal control epidermis(t =9.88,P ＜ 0.001 ) and in the percentage of CD68+ cells in nucleated cells between the superficial dermis of lesions and control skin(62％ ± 12％ vs.70％ ± 14％,t =2.66,P ＜ 0.05).The density of dermal CD68+ histiocytes was similar between the lesions and control skin ((287 ± 73) cells/mm2 vs.(290 ± 22) cell/mm2,t =0.02,P ＞ 0.05).Conclusions In keloid lesions,Langerhans cells decrease in the epidermis but increase in the dermis,CD68+ histiocytes are absent in the epidermis,and reduced in the dermis with a declined percentage in nucleated cells.
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Objective To investigate the molecular transduction mechanisms of apoptosis in cuta-neous squamous cell carcinoma cell line SCL-1 induced by acitretin. Methods SCL-1 cells were cultured and continuously treated with various concentrations of acitretin. Apoptosis was assessed by enzyme-linked immunosorbent assay (ELISA) in these cells on day 1, 3 and 5. Apoptotic cells were observed by acridine orange staining on day 5. The protein expressions of Fas, FasL, Fas-associated death domain (FADD), cas-pase-8, caspase-3 and poly ADP-ribose polymerase (PARP) were examined using Western blot in SCL-1 cells treated with acitretin at 1 x 105 mol/L at different time points. Neutralizing anti-Fas antibody (ZB4,1 μg/mL) was utilized to pretreat SCL-1 cells before the treatment with acitretin, following that, ELISA was done to compare the apoptosis in cells treated with ZB4, acitretin, or the combination of ZB4 and acitretin,respectively. Results Acitretin induced the apoptosis of SCL-1 cells in a dose- and time-dependent manner.Morphologically, acitretin-treated SCL-1 cells showed a typical characteristic of apoptosis. Significant increase in Fas, FasL, and FADD protein expression, as well as the activation of caspase-8, caspase-3 and PARP were induced by the treatment with acitretin. The apoptosis absorbance value was 0.78 ± 0.04 in cells treated with acitretin alone, decreased to 0.41 ± 0.03 in cells treated with ZB4 and acitretin (P ＜ 0.05), .suggesting that ZB4 could block the apoptosis of SCL-1 cells inducedby acitretin. Conclusion Acitretin could induce the apoptosis of cutaneous squamous cell carcinoma cells likely by Fas signaling pathway.
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Objective To investigate the effects ofthrce generations oftretinoids on the apoptosis of and caspase expressions in human cutaneous squamous cell carcinoma cell line SCL-1. Methods SCL-1 cells were cultured in vitro in the presence of three tretinoins, namely all-trans retinoic acid (ATRA), acitrefln and tazarotene at a concentration of 1×10-5 mol/L. On day 1, 3, 5, MTT assay and ELISA were used to detect the cell proliferation and apoptosis of these SCL-1 cells respectively; on day3, flow cytometry with Annexin V/PI was applied to analyze the cell cycle and early apoptosis, Western blot to measure the protein expressions of caspase-8 and caspase-9 in these cells. Results The growth of SCL-1 cells could be inhibited by ATRA, acitretin or tazarotene of 1×10-5 mol/L in a time-dependent manner (all P<0.01). All the three tretinoids could induce the cell apoptosis of SCL-1 cells (P<0.01), arrest them in G1-phase, and activate caspase-8 and caspase-9 (F=35.50, 25.79, respectively, both P<0.01). Of the three tretinoins, acitretin exerted the strongest effect on all the parameters tested. Conclusions Tretinoins can inhibit the growth and induce the apoptosis of cutaneous squamous carcinoma cells, which may be mediated through Fas- and mitochondria-way.
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Objective To investigate the relationship of CAG repeat length polymorphism in the androgen receptor(AR)gene to the development of acne.Methods A total of 238 patients with ache vulgaris and 207 healthy human controls in Northeast China were included in this study.Genomic DNA was isolated and purified from the blood of these subjects.The CAG repeat lengths in the AR gene were analyzed by somatic microsatellites (STRs).Results A significant difference was found in the CAG repeat number between the male acne Patients(22.70±3.09)and male controls(23.48±2.83,P=0.046),but not between the female cases and controls(23.41±2.87 versus 23.85±0.21.P=0.12).In order to assess the risk associated with CAG repeats,the male and female subjects were dichotomized based on the median repeat length in the corresponding control group as the arbitrary cut-off point.Those men and women with a short CAG repeat length(＜23 in men,and＜24 in women)had a significantly increased risk for agne than those with a long CAG repeat length(men:95%confidence interval,1.21-3.54,OR=2.07,P=0.008;women:95%confidence interval.1.18-3.56,OR=2.05,P=0.01).Conclusions This study strongly indicates that the CAG repeat length in AR gene is associated with the development of acne in Northeast China,and those men with a short CAG repeat length seem to have a high risk for ague.Consequently,CAG repeat length may serve as a genetic susceptibility marker.