WTAP-Mediated N6-Methyladenosine of RNAs Facilitate the Pathophysiology of Atopic Dermatitis.

N6-methyladenosine (m6A) is the most abundant dynamic and reversible internal chemical modification of RNA in eukaryotic cells and is essential in multiple pathophysiological processes. However, it has not been reported in atopic dermatitis (AD). We used Arraystar m6A-mRNA epitranscriptomic microarray to screen for differentially expressed genes and their m6A levels and m6A-related enzymes in patients with AD. We confirmed that the m6A RNA methyltransferase WTAP and 2 candidate differentially expressed genes (S100A9 and SERPINB3) were significantly upregulated in keratinocytes in public data and epidermal lesions of patients with AD. In vitro cell experiments confirmed that WTAP influenced the expression of the 2 candidate differentially expressed genes and promoted primary human epidermal keratinocyte proliferation while inhibiting human epidermal keratinocyte differentiation. Furthermore, we showed that WTAP, S100A9, and SERPINB3 expression correlated with AD severity. Our findings revealed that WTAP-mediated m6A modification promoted the expression of S100A9 and SERPINB3 to aggravate human epidermal keratinocyte proliferation and dysdifferentiation contributing to the pathophysiological development of AD.

The impact of the COVID-19 pandemic on undergraduate and postgraduate students: A cross-sectional survey.

Background: The COVID-19 pandemic has impacted many facets of life. This study focuses on undergraduate and postgraduate students in China to explore how the pandemic has affected health status, daily life, learning situations, graduation-related situations, and their studies or work planning. Methods: This study sent online questionnaires to 2,395 participants to investigate the extent to which they were affected by the epidemic in the various aspects mentioned above and to understand what help they tend to get in the face of these effects. Results: A total of 2,000 valid questionnaires were collected. The physical health of 82.90% of the respondents was affected to varying degrees, with male students, non-medical students, and graduates being more affected than female students, students with medical majors, and non-graduates, respectively. The proportion of students affected by mental health, the total amount of physical exercise, emotional life, and interpersonal communication was 86.35, 88.65, 80.15, and 90.15%, respectively. Compared with medical students and non-graduates, non-medical students and graduates were more affected. In addition, students' learning and graduation conditions have also been affected to a certain extent: 13.07% of students may not be able to graduate on time, and the proportion of postgraduate students' graduations affected was higher than that of undergraduate students. Conclusion: The COVID-19 pandemic has affected the health status of students, their daily lives, learning situations, and so on to varying degrees. We need to pay attention to the issues, provide practical solutions, and provide a basis for better responses to similar epidemics in the future.

Identify the immune characteristics and immunotherapy value of CD93 in the pan-cancer based on the public data sets.

CD93 is a transmembrane receptor that is mainly expressed on endothelial cells. A recent study found that upregulated CD93 in tumor vessels is essential for tumor angiogenesis in several cancers. However, the underlying mechanisms are largely unexplored. Our present research systematically analyzed the characteristics of CD93 in tumor immunotherapy among 33 cancers. CD93 levels and co-expression of CD93 on cancer and stromal cells were detected using public databases and multiple immunofluorescence staining. The Kaplan-Meier (KM) analysis identified the predictive role of CD93 in these cancer types. The survival differences between CD93 mutants and WT, CNV groups, and methylation were also investigated. The immune landscape of CD93 in the tumor microenvironment was analyzed using the SangerBox, TIMER 2.0, and single-cell sequencing. The immunotherapy value of CD93 was predicted through public databases. CD93 mRNA and protein levels differed significantly between cancer samples and adjacent control tissues in multiply cancer types. CD93 mRNA expression associated with patient prognosis in many cancers. The correlation of CD93 levels with mutational status of other gene in these cancers was also analyzed. CD93 levels significantly positively related to three scores (immune, stromal, and extimate), immune infiltrates, immune checkpoints, and neoantigen expression.. Additionally, single-cell sequencing revealed that CD93 is predominantly co-expressed on tumor and stromal cells, such as endothelial cells, cancer-associated fibroblasts (CAFs), neutrophils, T cells, macrophages, M1 and M2 macrophages. Several immune-related signaling pathways were enriched based on CD93 expression, including immune cells activation and migration, focal adhesion, leukocyte transendothelial migration, oxidative phosphorylation, and complement. Multiple immunofluorescence staining displayed the relationship between CD93 expression and CD8, CD68, and CD163 in these cancers. Finally, the treatment response of CD93 in many immunotherapy cohorts and sensitive small molecules was predicted from the public datasets. CD93 expression is closely associated with clinical prognosis and immune infiltrates in a variety of tumors. Targeting CD93-related signaling pathways in the tumor microenvironment may be a novel therapeutic strategy for tumor immunotherapy.

Characteristics of lung metastasis in testicular cancer: A large-scale population analysis based on propensity score matching.

Background: This study aims to systematically evaluate predictive factors for lung metastasis (LM) in patients with testicular cancer (TC) and to investigate cancer-specific survival (CSS) and overall survival (OS) of LM in TC patients based on a large population-cohort. Methods: A total of 10,414 patients diagnosed with TC during 2010-2015 were adopted from the Surveillance, Epidemiology, and End Results (SEER). After propensity score matching (PSM), 493 patients with LM were included for subsequent analysis. Univariate and multivariate logistic regression analyses were employed to identify risk factors, a nomogram was developed, and the receiver operating characteristic (ROC) curve was utilized to confirm the validation of the nomogram. Prognostic factors for OS and CSS among TC patients with LM were estimated via Cox proportional hazards models. Results: Postmatching indicated that 11 parameters were successfully balanced between both groups (P > 0.05). After PSM, TC patients with LM presented an undesirable prognosis in both CSS and OS than those without LM (P < 0.001). The logistic regression model showed that tumor size; T stage; N stage; liver, brain, and bone metastases; and histology were positively associated with LM (P < 0.05). A nomogram was developed to predict diagnostic possibilities based on the independent risk variables, and the ROC curve verified the predictive capacity of the logistic regression model [area under the curve (AUC) = 0.910]. Conclusion: The selected variates in the nomogram can be predictive criteria for TC patients with LM. Brain metastasis, liver metastasis, and larger tumor size were prognostic factors for CCS and OS among TC patients with LM.

Proton pump inhibitors-related subacute cutaneous lupus erythematosus: Clinical characteristics, management, and outcome.

PURPOSE: Previous knowledge about the association between proton pump inhibitors (PPIs) exposure and subacute cutaneous lupus erythematosus (SCLE) was mainly based on limited case reports or few review studies. We aim to evaluate the clinical characteristics, management, and outcome in patients with PPIs-induced SCLE. METHODS: Case reports and case series from 2000 to December 31, 2021, on SCLE induced by PPIs were collected and retrospectively analyzed. RESULTS: A total of 29 patients (6 male and 23 female) were included from 19 studies, the median age was 61 years (range 19-85), and 65.5% of patients were ≥60 years old. 37.9% of patients had the history of autoimmune diseases. The incubation period of PPIs intro to SCLE was 6 weeks for PPI-naive patients and 2 weeks for those re-administration of PPIs. The most common symptoms were annular and polycyclic erythematous (74.1%), rash or maculopapular (48.1%), and scaly plaques (40.7%). Trunk (69.2%), extremities (69.2%), face (26.9%), chest (26.9%), and back (26.9%) were common involved locations. Antinuclear antibodies, anti-Ro/SSA antibodies, and anti-La/SSB antibodies were positive in 24 patients (82.8%), 24 patients (82.8%), and 6 patients (20.7%), respectively. Direct immunofluorescence was positive in 50% of cases. Complete clinical remission (92.6%) was observed (median time: 4 weeks) with discontinuation of PPIs and treatment of oral corticosteroids (61.1%), hydroxychloroquine (44.4%), or topical steroids (16.7%). CONCLUSION: PPIs-related SCLE is a rare adverse reaction based on clinical manifestations associated with immunological abnormalities and suggestive histological findings. PPIs should be suspected when considering possible culprits for drug-related SCLE.

CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway.

BACKGROUND: Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. METHODS: Epidermal CD147-overexpression or knockout (EpiCD147-OE or EpiCD147-KO) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. RESULTS: We found that specific overexpression of CD147 in the epidermis (EpiCD147-OE) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in EpiCD147-OE transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in EpiCD147-OE transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of CD147D207-230. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. CONCLUSION: Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway.

DNA methylation regulatory patterns and underlying pathways behind the co-pathogenesis of allergic rhinitis and chronic spontaneous urticaria.

Background: Allergic rhinitis (AR) and chronic spontaneous urticaria (CSU) are often concurrent in patients. Changes in DNA methylation affect T cell biological processes, which may explain the occurrence and progression of comorbidity. However, downstream regulatory pathways of DNA methylation in two diseases and the underlying mechanisms have not been fully elucidated. Methods: The GSE50101, GSE72541, GSE50222 and OEP002482 were mined for the identification of differentially expressed genes (DEGs) or co-expressed genes and differentially methylated genes (DMGs) in AR and CSU patients. We applied GO analysis and consensus clustering to study the potential functions and signal pathways of selected genes in two diseases. GSVA and logistic regression analysis were used to find the regulatory pathway between DNA methylation and activation patterns of CD4+ T cells. Besides, we used the Illumina 850k chip to detect DNA methylation expression profiles and recognize the differentially methylated CpG positions (DMPs) on corresponding genes. Finally, we annotated the biological process of these genes using GO and KEGG pathway analysis. Result: The AR-related DEGs were found closely related to the differentiation and activation of CD4+ T cells. The DEGs or co-expressed genes of CD4+ T cells in AR and CSU patients were also clustered using GO and KEGG analysis and we got 57 co-regulatory pathways. Furthermore, logistic regression analysis showed that the regulation of cellular component size was closely related to the activation of CD4+ T cells regulated by DNA methylation. We got self-tested data using the Illumina 850k chip and identified 98 CpGs that were differentially methylated in patients. Finally, we mapped the DMPs to 15 genes and found that they were mainly enriched in the same CD4+T cell regulating pathway. Conclusion: Our study indicated that DNA methylation affected by pollen participated in the activation patterns of CD4 + T cells, providing a novel direction for the symptomatic treatment of the co-occurrence of AR and CSU.

Application of blended teaching model based on SPOC and TBL in dermatology and venereology.

BACKGROUND: In this study, we applied the small private online course (SPOC) and team-based learning (TBL) blended teaching model to dermatology and venereology to ensure a higher quality learning experience for clinical medical students. METHODS: A total of 52 fifth-grade clinical undergraduates from Xiangya School of Medicine of Central South University were randomly divided into an experimental (n = 26) and a control group (n = 26). In March 2018, we used the SPOC and TBL blended teaching model in the experimental group and explored the effects of innovative teaching in the dermatology and venereology course, compared with the control group receiving the conventional teaching method. We analyzed the two groups' theoretical assessment scores and questionnaire results to evaluate the efficiency of the new pedagogy. RESULTS: Students in the experimental group had a better understanding than the control group of the dermatology and venereology content and higher scores on the case analysis questions in the final theoretical examination. The results revealed that the majority of the experimental group students agreed that the novel teaching model blended with SPOC&TBL helped them significantly stimulate motivation and develop their ability in self-directed learning, independent thinking, literature retrieval, presentation board, teamwork, communication, and systematic clinical thinking. The teaching satisfaction survey of the two groups showed that the students' satisfaction in the experimental group was significantly higher than in the control group (p < 0.05). CONCLUSIONS: The SPOC&TBL teaching model is better than the traditional one in enriching students' professional knowledge and cultivating their comprehensive ability. It can effectively promote educational quality, improve students' learning effects, and enhance their satisfaction. This method has broad application prospects.

Photodynamic therapy should be considered for the treatment of folliculitis decalvans.

BACKGROUND: Different therapies such as clindamycin, rifampicin, isotretinoin, or corticosteroids have been used for folliculitis decalvans with poor results. Recently, PDT has been used for treating folliculitis decalvans more frequently. However, the efficacy of PDT for treating folliculitis decalvans is lacking consensus. In this study, we conducted a retrospective analysis to evaluated the status of PDT for the treatment of folliculitis decalvans. METHODS: 13 cases of folliculitis decalvans patients were treated with ALA-PDT. The treatment totals 3 times, and the interval between each treatment was 10-14 days. A follow-up was conducted at 12 months after the last treatment. The condition was graded according to the following evaluation criteria: recovery, significant improvement, moderate improvement, ineffective. RESULTS: A total of 7 cases improved significantly, and 6 cases improved moderately followed the first treatment. After the second treatment, 10 cases showed significant improvement, and 2 cases responded poorer than the first treatment. After the third treatment, 4 cases recovered, 7 cases improved significantly, and 2 case moderately improved. At the 12-months follow-up, 9 out of 13 patients were well controlled and with no recurrence. The other 4 patients relapsed. CONCLUSION: In summary, photodynamic therapy shows overall favorable effect on folliculitis decalvans and should be considered as a method for the treatment of folliculitis decalvans.

Application and challenge of reflectance confocal microscopy in the diagnosis of pigmented nevus.

OBJECTIVE: To investigate the application and challenge of reflectance confocal microscopy (RCM) in the diagnosis of pigmented nevus. METHOD: A total of 997 patients with clinical diagnosis of pigmented nevus were included in the study, and RCM imaging was performed on the lesion of each patient. A biopsy was performed in 78 of these patients for histological diagnosis. We retrospectively analyzed the results of RCM diagnosis and histological diagnosis and then found the RCM characteristics of the histologically confirmed lesion. RESULTS: According to the RCM images, 823 of the 997 (82.55%) patients were diagnosed with pigmented nevus, while 113 (11.33%) were not diagnosed by dermatologists using RCM. Of the 78 biopsy lesions, 36 of the 46 (78.26%) cases diagnosed with pigmented nevus were consistent with histological diagnosis, while three were rediagnosed with dermatofibromas, four were seborrheic keratosis, one was malignant melanoma in situ, and two were lentigo. CONCLUSION: RCM exhibits a high diagnostic accuracy for patients with clinical diagnosis of pigmented nevus. However, due to the limitation of RCM scanning depth and the commonality of the microscopic characteristics of related diseases, RCM still faces certain challenges in the diagnosis of pigmented nevus.

Ozone therapy promotes the differentiation of basal keratinocytes via increasing Tp63-mediated transcription of KRT10 to improve psoriasis.

Psoriasis is a chronic immune-mediated inflammatory dermatosis. Recently, ozone therapy has been applicated to psoriasis treatment; however, the mechanism by which ozone therapy improves psoriasis remains unclear. The excessive proliferation and the differentiation of basal keratinocytes have been considered critical issues during pathological psoriasis process, in which keratin 6 (KRT6) and KRT10 might be involved. In the present study, KRT6, IL-17 and IL-22 protein within psoriasis lesions was decreased, while KRT10 and Tp63 protein in psoriasis lesions was increased by ozone treatment in both patient and IMQ mice psoriatic tissues. In the meantime, ozone treatment down-regulated KRT6 mRNA and protein expression while up-regulated KRT10 mRNA and protein expression within IL-22 treated primary KCs; the cell viability of KCs was suppressed by ozone treatment. Moreover, Tp63 bound to KRT10 promoter region to activate its transcription in basal keratinocytes; the promotive effects of ozone on Tp63 and KRT10 were significantly reversed by Tp63 silence. Both TP63 and KRT10 mRNA expression were significantly increased by ozone treatment in psoriasis lesions; there was a positive correlation between Tp63 and KRT10 expression within tissue samples, suggesting that ozone induces the expression of Tp63 to enhance the expression of KRT10 and the differentiation of keratinocytes, therefore improving the psoriasis. In conclusion, the application of ozonated oil could be an efficient and safe treatment for psoriasis; ozone promotes the differentiation of keratinocytes via increasing Tp63-mediated transcription of KRT10, therefore improving psoriasis.

BCL-6 suppresses miR-142-3p/5p expression in SLE CD4+ T cells by modulating histone methylation and acetylation of the miR-142 promoter.

The reduced expression of miR-142-3p/5p in CD4+ T cells of SLE patients caused T cell hyperactivity and B cell hyperstimulation. This study aimed to investigate the mechanisms of regulating miR-142-3p/5p expression in SLE CD4+ T cells. The BCL-6 expression was significantly increased in SLE CD4+ T cells compared with normal controls, and the BCL-6 expression was inversely correlated with miR-142-3p/5p expression. BCL-6 suppresses the expression of miR-142-3p/5p by increasing H3K27me3 level and reducing H3K9/K14ac levels in SLE CD4+ T cells. BCL-6 regulates histone modifications in miR-142 promoter by recruiting EZH2 and HDAC5. Furthermore, we observed significantly decreased CD40L, ICOS, and IL-21 expression levels in SLE CD4+ T cells with BCL-6 interference, and obviously reduced autoantibody IgG production in autologous B cells co-cultured with BCL-6 inhibited SLE CD4+ T cells. Our study found that increased BCL-6 up-regulates H3K27me3 and down-regulates H3K9/14ac at miR-142 promoter in SLE CD4+ T cells. These factors induce a declination in miR-142-3p/5p expression, consequently resulting in CD4+ T cell hyperactivity.

[Not Available].

OBJECTIVE: To evaluate the efficacy and influential factors for 308 nm excimer laser in the treatment of stable vitiligo patients.
 METHODS: A total of 207 stable vitiligo patients with 1 763 patches were treated with 308 nm excimer laser. Open-label study was carried out to investigate the efficacy and safety regarding the treatment with 308 nm excimer laser, and to compare the response under different conditions including gender, age, duration, lesion location, and hair color.
 RESULTS: After treatment, 560 (31.8%) patches achieved 100% repigmentation, 650 (36.9%) lesions showed 75%-99% repigmentation, 189(10.7%) showed 50%-75% repigmentation, 231(13.1%) showed 25%-49% repigmentation, 108(6.1%) showed 1%-24% repigmentation, 25(1.4%) displayed no response. The rates of total excellent response (50%-100% repigmentation) in underage patients was 86.9%, much higher than that in adult patients (P<0.001). Total excellent response rates was 90.6% in disease duration <2 years, and 40.7% in disease duration ≥2 years. Lesions on the faciocervical region responded better than trunk and limbs, showing 95.4%, 70.3%, and 41.7% total excellent response, respectively. Patients with poliosis showed 54.9% in total excellent response rate, much lower than 84.5% in patients without poliosis(P<0.001). No significant response differences in gender were found.
 CONCLUSION: 308 nm excimer laser is effective and safe in treatment of vitiligo. Aging, disease duration, lesion location, and hair color in lesion may be the influential factors for 308 nm excimer laser in treatment of vitiligo patients.

Tandem repeats of TSER significantly influence the efficacy of 5-fluorouracil in the treatment of plantar warts.

AIM: To identify potential genetic risk markers associated with 5-fluorouracil (5-FU) treatment outcomes in plantar warts patients. METHODS: In this study, 126 plantar warts patients were treated with an intralesional mixture of 5-FU, lidocaine and epinephrine. Treatment outcomes were compared with DNA mutation analysis. RESULTS: More patients with TSER 3R/3R genotype failed 5-FU treatment than TSER 2R/3R+2R/2R (72.1 vs 43.8%; odds ratio: 3.32; 95% CI: 1.26-8.72; p = 0.013). In addition, the regression modeling identified patient age and TSER 3R allele as covariates of the risk of 5-FU treatment failure (p = 0.025). CONCLUSION:  TSER 3R/3R of TYMS gene was found to be the major risk of treatment failure. This genetic marker provides a potential treatment stratification target to modulate 5-FU treatment in plantar wart patients.

[Application of Confocal Laser Scanning Microscopy in Detection of Demodex Mites].

Objective: To explore the application value of confocal laser scanning microscopy（CLSM） for detection of facial Demodex mites. Methods: One hundred and twenty patients without basic diseases visiting the Department of Dermatology of the Third Xiangya Hospital for papules, pustules, erythema, and scales and suspected to have facial demodicosis were selected. Basic information and types of facial lesion were recorded. CLSM was performed to examine Demodex infection. Twenty patients with positive infection as indicated by CLSM were randomly selected for further verification with microscopy. Results: Among the 120 patients, 59 were positive for facial demodicosis as indicated by CLSM, with a detection rate of 49.2%, 61.1% of males and 39.4% of females. The 20 patients with further microscopic examination were all diagnosed as Demodex folliculorum infection. Among the 120 patients, the Demodex detection rate showed a trend of increase with age, with the highest rate （72.7%, 16/22） in the group of 40-49 yearsï¼»P<0.05 versus the 21.1% （4/19） in the group of 10-19 years and the 37.8% （14/37） in 20-29ï¼½. In addition, there was a significant difference in the percentage of patients with ＜5 mites and ≥5 mites in area of 4 mm×4 mm between type I （mainly erythema and scales）（80.6%, 29/36; 19.4%, 7/36, respectively; P<0.01） and type II lesions （mainly papules and pustules） （52.2%, 12/23; 47.8%, 11/23, respectively; P>0.05）（P<0.05）. Conclusion: CLSM is an efficient technique for detecting facial Demodex, and is advantageous as it offers in-situ, noninvasive, painless, real-time and dynamic detection.

Association of FCER1A genetic polymorphisms with risk for chronic spontaneous urticaria and efficacy of nonsedating H1-antihistamines in Chinese patients.

Antihistamines are the first-line treatment for chronic urticaria (CU). However, some CU patients are relatively refractory to antihistamines. The mechanism underlying the interindividual variation is still unknown. The α-chain of the high-affinity IgE receptor is crucial to the IgE-mediated allergic response. The present study is to investigate whether FCER1A polymorphisms are associated with the risk of CSU, and to determine whether these polymorphisms influence the therapeutic efficacy of nonsedating H1-antihistamines. 191 CSU patients treated by nonsedating H1-antihistamines monotherapy (including desloratadine, mizolastine or fexofenadine) were prospectively enrolled in this study. The response to antihistamines monotherapy was assessed by urticaria activity score (UAS7) after 4 weeks of treatment. FCER1A rs2298805, rs10908703 and rs2494262 genotypes were determined by Sequenom Mass Array technology or direct sequencing. There was significant difference in the allele frequency of rs2298805A between CSU patients and 177 healthy subjects (5.3 vs 10.2 %, P = 0.012, OR = 0.491, 95 % CI 0.278-0.865), and also significant difference in the allele frequency of rs2298805A between effective and ineffective groups (7.5 vs 1.0 %, P = 0.015, OR = 8.328, 95 %CI 1.1-63.039). In addition, rs2298805 polymorphism was significantly associated with total serum IgE concentrations (P = 0.011). There were no differences in the rs10908703 and rs2494262 either between CSU patients and healthy controls, or between effective and ineffective groups. These data suggest that rs2298805 might be associated with risk for CSU and the therapeutic efficacy of nonsedating H1-antihistamines in Chinese patients with CSU.

Influence of component 5a receptor 1 (C5AR1) -1330T/G polymorphism on nonsedating H1-antihistamines therapy in Chinese patients with chronic spontaneous urticaria.

BACKGROUND: The nonsedating H1-antihistamines are the first-line medicines for chronic spontaneous urticaria (CSU) patients. However, not all these patients respond well to the antihistamines, and the mechanisms underlying the interindividual differences are still unclear. C5AR1 gene encodes the component 5a receptor (C5aR) protein, which has been reported to play an important role in chronic spontaneous urticaria. OBJECTIVE: This study aimed to investigate whether the single nucleotide polymorphisms (SNPs) in C5AR1 are associated with CSU susceptibility and antihistamines therapeutic efficacy in Chinese CSU patients. METHODS: A total of 191 CSU patients and 102 healthy controls were prospectively studied in our study. CSU patients were treated by nonsedating H1-antihistamines monotherapy for 4 weeks. The C5AR1 -1330T/G (rs11673309) genotype was determined by Sequenom Massarray. RESULTS: Among these 191 CSU patients, there were 114 patients who were treated with desloratadine, 65 were treated with mizolastine, and 12 with fexofenadine. The-1330T alleles in CSU patients were significantly higher than controls (0.555 vs. 0.466, P=0.040, OR=1.429 [1.016-2.010]). The poorest response to desloratadine was observed in heterozygotes, when compared with either GG or TT homozgote (P=0.001). However, there was no significant difference in three genotypes when treated with mizolastine group (P=0.215). CONCLUSION: We concluded that the C5AR1 SNP -1330T/G may serve as a useful pharmacodynamic predictor of nonsedating H1-antihistamines efficacy in CSU patients, and -1330T alleles may be taken as a risk factor for the CSU.

Overexpression of HMGB1 in melanoma predicts patient survival and suppression of HMGB1 induces cell cycle arrest and senescence in association with p21 (Waf1/Cip1) up-regulation via a p53-independent, Sp1-dependent pathway.

Although laboratory studies have implicated the high mobility group box 1 (HMGB1) in melanoma, its clinical relevance remains unclear. We analyzed nearly 100 cases of human melanoma and found that HMGB1 was highly overexpressed in melanoma samples relative to normal skin and nevi tissues. Significantly, higher levels of HMGB1 correlated with more advanced disease stages and with poorer survival in melanoma patients. Unlike the well-documented pro-inflammatory role of the extracellular HMGB1, we found that its intracellular activity is necessary for melanoma cell proliferation. An absolute dependency of melanoma cell proliferation on HMGB1 was underscored by the marked response of cell cycle arrest and senescence to HMGB1 knockdown. We demonstrated that HMGB1 deficiency-induced inhibition of cell proliferation was mediated by p21, which was induced via a Sp1-dependent mechanism. Taken together, our data demonstrate a novel oncogenic role of HMGB1 in promoting human melanoma cell proliferation and have important implications in melanoma patient care.