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Objective:To investigate immune effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) on mouse models of cutaneous squamous cell carcinoma (cSCC) .Methods:Ultraviolet-induced SKH-1 hairless mouse models of cSCC were established, and 40 tumor-bearing mice were randomly and equally divided into several groups: control group receiving no treatment, and 7 treatment groups treated with ALA-PDT for 1, 3, 6, 12 and 24 hours, as well as 3 and 7 days respectively. After treatment, these mice were sacrificed at different time points, and skin tissues measuring 5 mm 3 in size were resected. Immunohistochemical study and flow cytometry were performed to detect local infiltration of immune cells in cSCC tissues at different time points, including neutrophils, macrophages, T cells, B cells, natural killer cells and dendritic cells. Statistical analysis was done by the two-sample t test using SPSS 16.0 software. Results:The number and proportion of local neutrophils and macrophages showed the most significant increase in mouse cSCC tumors 1 hour after ALA-PDT compared with those before treatment (immunohistochemical results [number of cells per 400 × field]: 61.22 ± 6.65 vs. 22.56 ± 4.13, 59.67 ± 4.30 vs. 21.89 ± 3.26, respectively, both P < 0.05; flow cytometry results: 35.64% ± 15.33% vs. 5.46% ± 2.44%, 12.15% ± 4.86% vs. 1.98% ± 1.49%, respectively, both P < 0.05) . Both immunohistochemical study and flow cytometry showed that the expression of T cells, B cells, natural killer cells and dendritic cells significantly increased in cSCC tissues 6 hours after treatment (all P < 0.05) . After reaching the peak, the number and proportion of the above-mentioned cells decreased in cSCC tissues, but were still higher than those before treatment, and the increase continued until the end of this study, that is, day 7 after treatment. Conclusion:ALA-PDT may exert anti-tumor effects by recruiting immune cells, especially neutrophils and macrophages.
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Objective:To investigate clinical manifestations and dermoscopic characteristics of lichen planus-like keratosis (LPLK) .Methods:Clinical data were collected from 21 patients with LPLK who visited Shanghai Skin Disease Hospital and underwent both dermoscopic and histopathological examinations from January 2017 to September 2019, and clinical and dermoscopic features were retrospectively analyzed.Results:These patients were aged 64.69 ± 13.29 years, and the ratio of males to females was 1∶2. Skin lesions were located on the face of 18 cases and legs of 3 cases, and were red/violaceous in color in 7 cases, reddish-brown in 5, brown/gray in 8, and brown/reddish in 1. There were 3 types of skin lesions, including plaque-like type in 10 cases, flat pigmented patch type in 6, and flat erythema-like type in 5. As dermoscopy showed, 12 cases were non-pigmented LPLK, and 9 were pigmented LPLK. Pigment granules were found in 13 lesions, and there was no significant difference in the prevalence of pigment granules between pigmented and non-pigmented LPLK ( P=0.07) ; pigment granules were often diffusely distributed (9/13) , and the diffuse distribution pattern was common paticularly in pigmented LPLK (8/9) ; locally distributed pigment granules were found in 4 cases of non-pigmented LPLK. Coarse pigment granules were seen in 10 cases (10/13) , including 8 of pigmented LPLK and 2 of non-pigmented LPLK, and the prevalence rate of coarse pigment granules significantly differed between the pigmented LPLK and non-pigmented LPLK groups ( P=0.002) . Moreover, special distribution patterns of pigment granules included the annular granular pattern (8/13) and peppered pattern (7/13) , and no significant difference was observed in the prevalence of the 2 special distribution patterns between the pigmented LPLK and non-pigmented LPLK groups (both P > 0.05) . Scales were seen in 13 cases (13/21) , and vascular structures in 7 (7/21) , and there was no significant difference in the prevalence of the 2 structures between the pigmented and non-pigmented LPLK groups ( P=0.67, 0.16, respectively) . Conclusions:LPLK mostly occurs on the face, and manifests as solitary red, reddish-brown or brownish-gray plaques or patches, whose surfaces may be covered with scales. The characteristic dermoscopic feature of LPLK is the presence of pigment granules, which are coarse, often diffusely distributed, and commonly observed in pigmented LPLK.
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Objective:To establish a model for predicting the mental health status of nurses based on machine learning algorithm.Methods:In February 2020, the nurses from Shantou Central Hospital and Cancer Hospital of Shantou University Medical College were recruited by convenience sampling, investigated using the Self-reporting Inventory, Coping Style Questionnaire, Social Support Rating Scale and Work Attitude Scale. Mental health status was treated as a dichotomous variable, and candidate predictors were screened out by univariate and multivariate Logistic regression analysis. The subjects were randomly divided into a training set (80%) and a test set (20%). Then five prediction models of nursing staff mental health status were constructed using the five machine learning methods (Logistic Regression, Artificial Neural Network, C5.0 Decision Tree, Bayesian Network and Support Vector Machine), verified and compared to screen out the model with the highest predictive efficiency.Results:A total of 415 nurses were enrolled, and the positive detection rate of mental health symptoms was 20.48%. According to univariate and multiple Logistic regression analysis, candidate predictors were work attitude ( OR=1.098, 95% CI 1.028-1.174), self-accusation ( OR=7.703, 95% CI 2.014-29.468), problem-solving( OR=0.131, 95% CI 0.025-0.686), the number of night shifts per month ( OR=0.204, 95% CI 0.073-0.573)and support availability ( OR=0.830, 95% CI 0.701-0.984). The accuracy of prediction of Logistic Regression, Artificial Neural Network, C5.0 Decision Tree, Bayesian Network and Support Vector Machine were 84.21%, 85.53%, 82.89%, 78.95%, 84.21%. The area under the ROC curve was 0.801, 0.825, 0.777, 0.583, 0.774. Artificial Neural Network was significantly more effective than Logistic regression, C5.0 Decision Tree, Bayesian Network and Support Vector Machine (DeLong test, P<0.05). Conclusions:The machine learning based predictive models for nursing staff mental health status has higher predictive value, which can be applied into nursing staff mental health screening decisions to accurately grasp its dynamic changes, early identification of high-risk mental health abnormalities and early intervention. Work attitude, self-accusation, problem-solving, the number of night shifts per month and support availability was predictors to construct predictive models.
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Photoacoustic imaging is a kind of non-invasive technology without ionizing radiation that can be used to image optical absorbers in tumor tissues according to the principle of "light in and sound out". It has the advantages of high contrast of optical imaging as well as high penetrability of acoustic imaging. However, current researches on photoacoustic imaging are still limited in the laboratory. This technology can be used for detection of cutaneous melanoma in situ and non-melanoma skin cancer, sentinel lymph node imaging, detection and eradication of circulating tumor cells by combining real-time laser ablation technique, and versatile imaging and treatment with the aid of exogenous imaging agents. This review summarizes preclinical experiments about photoacoustic imaging technology in skin tumors, with a view to promoting its clinical application at an early date.
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OBJECTIVE@#To explore the genetic basis for a sporadic case with neurofibromatosis type 1 (NF1).@*METHODS@#Peripheral blood samples were collected from the patient, his unaffected parents and 100 healthy controls. The NF1 gene was detected by PCR and direct sequencing.@*RESULTS@#The patient was found to carry a novel nonsense variant c.4339C>T (p.Q1447X) in exon 33 of the NF1 gene. The same variant was not found in his unaffected parents and the 100 healthy controls.@*CONCLUSION@#The c.4339C>T (p.Q1447X) variant probably underlies the pathogenesis of NF1 in this patient.
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Objective To establish a photoacoustic detection system and data processing methods for skin tumors,and to explore photoacoustic imaging and photoacoustic spectrum in mouse models of cutaneous squamous cell carcinoma (CSCC).Methods A total of 60 healthy specific pathogen-free (SPF) female BALB/C nude mice aged 6-8 weeks were randomly and equally divided into 2 groups to be inoculated with a murine CSCC cell line XL50 and a human CSCC cell line A431 respectively on the right back near the upper limbs,and mouse models of murine CSCC (n =20) and human CSCC (n =20) were successfully established.The 850-nm photoacoustic detection system was applied in the above 2 kinds of mouse models,and photoacoustic imaging and photoacoustic spectrum data were collected.The fitted slope of acoustic power spectrum curves was compared between squamous cell carcinoma tissues and normal skin on the left back of the mouse model.After the photoacoustic detection,tumor tissues and normal skin at the opposite side were excised from the 2 kinds of mouse models,and subjected to histopathological examination.The fitted slope of different tissues was compared by using t test.Results Photoacoustic imaging showed higher photoacoustic signals of hemoglobin in squamous cell carcinoma tissues compared with the normal skin tissues.In the model of murine CSCC,the fitted slope of acoustic power spectrum curve was significantly lower in the tumor tissues (-1.827 ± 0.153 1) than in the normal skin tissues (-1.059 ± 0.117 8,t =3.973,P ＜ 0.001).In the model of human CSCC,the fitted slope of acoustic power spectrum curve was also significantly lower in the tumor tissues (-1.537 ± 0.125 5) than in the normal skin tissues (-0.960 ± 0.259 7,t =2.166,P =0.043).Histopathological examination showed that the number of vessels increased in the tumor tissues compared with the normal skin tissues.Conclusion CSCC tissues are different from normal skin tissues in photoacoustic imaging signals and the fitted slope of acoustic power spectrum,which may lay a foundation for non-invasive photoacoustic diagnosis of CSCC.
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Objective To evaluate the protective effect of dietary n-3 polyunsaturated fatty acids (PUFA) on ultraviolet-induced acute skin photodamage in SKH-1 hairless mice,and to explore its mechanism.Methods Totally,50 SKH-1 hairless mice were equally divided into 5 groups to be fed with forages with the ratios of n-3 PUFA to fatty acid being 0,12.5％,25％,50％ and 100％ respectively (control group,12.5％,25％,50％ and 100％ n-3 PUFA groups).On day 8 after feeding,the back of mice in the 5 groups were irradiated by a solar ultraviolet simulator at 2 minimum erythema doses (MED) to establish an acute photodamage model.After 24 hours,cutaneous reactions on the back of mice were observed by naked eyes and dermoscopy,and skin biopsy specimens were subjected to hematoxylin and eosin (HE) staining for observing the epidermal structure,intercellular edema,inflammatory cell infiltration and photodamaged cells.Immunohistochemical staining was performed to determine the expression of inflammatory cytokines including interleukin-1 beta (IL-1β),IL-6 and tumor necrosis factor alpha (TNF-α),and enzyme-linked immunosorbent assay (ELISA) to measure the protein expression of the above 3 inflammatory cytokines in the tissue homogenate.Results Compared with the control group and 12.5％ n-3 PUFA group,the 25％,50％ and 100％ n-3 PUFA groups all showed a milder degree of acute skin photodamage,epidermis thickening,intercellular edema,and inflammatory cell infiltration.The number of photodamaged cells per high-power field (× 100) was significantly higher in the control group and 12.5％ n-3 PUFA group (17.50 ± 4.93,14.25 ± 1.71,respectively) than in the 25％,50％ and 100％ n-3 PUFA groups (6.50 ± 1.73,4.75 ± 2.06,4.50 ± 1.73,respectively;F =19.1,P ＜ 0.001).Immunohistochemical results showed that IL-1β,IL-6 and TNF-α were expressed to different extents in the epidermis and dermis among the 5 groups at 24 hours after ultraviolet radiation.Compared with the control group and 12.5％ n-3 PUFA group,the 25％,50％ and 100％ n-3 PUFA groups showed significantly lower expression of the above 3 inflammatory cytokines (P ＜ 0.001).ELISA revealed that the levels of IL-1β,IL-6 and TNF-α in the skin tissues of the mice were significantly lower in the 25％,50％ and 100％ n-3 PUFA groups than in the control group and 12.5％ n-3 PUFA group (P ＜ 0.05).Conclusions When the ratio of n-3 PUFA to fatty acid reaches more than 25％,dietary n-3 PUFA has protective effects against ultraviolet-induced acute photodamage,.Moreover,the higher the content of n-3 PUFA is,the stronger the protective effect is.It is suggested that n-3 PUFA may inhibit the inflammatory reaction through the arachidonic acid pathway.
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<p><b>OBJECTIVE</b>To detect mutations of the NF1 gene in two sporadic cases with neurofibromatosis type 1 (NF1) and explore their molecular mechanisms.</p><p><b>METHODS</b>Clinical data of the two patients was collected. Genomic DNA was extracted from peripheral blood samples. Specific primers were designed to exclude pseudogenes. PCR was performed to amplify all coding exons of the NF1 gene. PCR products were directly sequenced.</p><p><b>RESULTS</b>Two novel mutations of the NF1 gene (c.1019-1020delCT in exon 9 and c.7189G to A in exon 48) were respectively identified in the two patients but not among their unaffected parents or 100 healthy controls.</p><p><b>CONCLUSION</b>Mutations of the NF1 gene may have predisposed to the NF1 in the two patients.</p>
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<p><b>OBJECTIVE</b>To analyze the clinical and genetic features of 9 ethnic Han Chinese patients with disseminated superfacial actinic porokeratosis (DSAP).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples collected from the patients. PCR and direct sequencing were carried out for five patients from a family, 4 sporadic cases, and 120 healthy controls to identify potential mutations of four genes (MVK, MVD, PMVK, FDPS) involved in the mevalonate pathway as well as SLC17A9, SSH1, and SART3 genes. Pathogenecity of suspected mutations were assessed with SIFT, and Polyphen-2 scores.</p><p><b>RESULTS</b>A c.746T>C mutation was identified in the family and two sporadic cases, while a c.875A>G mutation was identified in another sporadic case. No mutation was identified in the remainder genes among all patients. Scoring has suggested that the c.746T>C and c.875A>G mutations of the MVD gene are probably pathogenic.</p><p><b>CONCLUSION</b>c.746 T>C and c.875A>G of the MVD gene are most common mutations. Skin rashes of the patients have a strong connection with the sunlight, albeit a significant difference among patients was discovered.</p>
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Aged, 80 and over , Female , Humans , Male , Middle Aged , Case-Control Studies , Mutation , Genetics , Pedigree , Porokeratosis , GeneticsABSTRACT
Objective To investigate the mechanisms underlying the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on cutaneous squamous cell carcinoma (SCC) in mice.Methods A model of cutaneous SCC was established in 21 SKH-1 hairless mice,which were treated with topical ALA 8％ cream followed by single irradiation with He-Ne laser at a total dose of 30 J/cm2 (ALA-PDT).Three mice were sacrificed before and at 1,3,6,12,24 hours and 7 days after the irradiation,separately,and SCC tissue was taken from the mice.Transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) were performed to determine the pattern of tumor cell death(necrosis,apoptosis and autophagy) during 1-24 hours after ALA-PDT,and immunohistochemical techniques were used to estimate the expressions of LC3B and CD34 on SCC cells,as well as the quantity of CD1a+ cells,CD4+ T and CD8+ T lymphocytes in SCC tissue 7 days after the irradiation.Statistical analysis was done by two-sample t test using SPSS 17.0 software.Results TEM showed gradual necrosis and apoptosis (especially necrosis) of tumor cells and formation of autophagosomes in macrophages within 24 hours after ALA-PDT.The number of apoptotic cells per high power field (× 400) in SCC tissue significantly increased at 24 hours compared with that before ALA-PDT (7.30 ± 2.18 vs.2.00 ± 0.69,P ＜ 0.05).As immunohistochemistry revealed,there was a significant decrease in the number of CD34+ cells (1.33 ± 0.58 vs.19.00 ± 2.66,P＜ 0.01),but a marked increase in that of CD1a+ ce1ls (23.01 ± 2.04 vs.10.33 ± 1.88,P＜ 0.05),CD4+ T cells (28.67 ± 1.76 vs.12.40 ± 2.27,P＜ 0.05),CD8+ T cells (25.79 ± 2.37 vs.11.67 ± 1.45,P ＜ 0.05) and LC3B+ interstitial cells (30.6 ± 3.21 vs.21.44 ± 4.3,P ＜ 0.05) per high power field (× 400) in SCC tissue on day 7 compared with that before ALA-PDT.Conclusions ALA-PDT may directly kill SCC cells by inducing cell necrosis and apoptosis rather than autophagy.Additionally,ALA-PDT can injure microvascular endothelial cells and cause the aggregation of dendritic cells,CD4+ T cells and CD8+ T cells in SCC tissue.
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Objective To evaluate the efficacy of light-emitting diode (LED) irradiation at 530 nm,630 nm and 850 nm in the treatment of photoaged skin.Methods A total of 14 adults with photoaged extensor forearm were recruited in this study.Three areas were selected at the extensor forearm in each of these subjects and received LED irradiation at 530 nm,630 nm and 850 nm,respectively,thrice a week for 12 sessions.Dermoscopy was used to visualize these areas before and after the irradiation,the Corueometer CM 825 to measure stratum corneum (SC) hydration,Tewameter TM 300 to determine transepidermal water loss (TEWL),and CM-2600d spectrophotometer to measure L* value and melanin index (MI).Tissue specimens were obtained from these areas irradiated with LED at 530 nm (n =5),630 nm (n =5) and 850 nm (n =4) separately before and 6 weeks after the initial irradiation,and subjected to histopathological examination.Results Both skin texture and pigmentation were improved in 10 and 7 testees after 12 sessions of LED irradiation at 630 nm and 850 nm,respectively,but the skin texture became rougher and pigmentation was increased in 7 testees after LED irradiation at 530 nm.After LED irradiation at 630 nm and 850 nm,the testees experienced an obvious increase in SC hydration ((37.9 ± 7.7) au and (34.5 ± 7.1) au at 6 weeks after the initial irradiation vs.(33.1 ± 6.1) au and (32.0 ± 7.0) au before irradiation,both P ＜ 0.05),but a significant decrease in TEWL value ((9.8-± 2.5) and (10.9 ± 2.5) g·m-2·h-1 at 6 weeks after the initial irradiation vs.(14.0 ± 1.8) and (14.2 ± 2.6) g·m-2·h-1 before irradiation),with no significant changes in L* value or MI (both P ＞ 0.05).No evident alteration was observed in SC hydration or TEWL value (both P ＞ 0.05),while the L* value significantly decreased (P ＜ 0.05) and MI increased (P ＜ 0.05) after LED irradiation at 530 nm.Histopathological examination showed photo-induced denaturation of collagen fibers and elastic fibers in the dermis of these subjects before irradiation,as well as nascent collagen fibers and elastic fibers in a more dense and regular arrangement after irradiation at the three wavelengths.Conclusions LED irradiation at both 630 nm and 850 nm can improve the appearance and barrier function of,and stimulate the proliferation and rearrangement of collagen fibers and elastic fibers in,photoaged skin,while LED irradiation at 530 nm increases skin pigmentation.