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Pemphigus vulgaris (PV) is a chronic and potentially life-threatening autoimmune blistering disease. Aberrant mTOR pathway activity is involved in many autoimmune diseases. This study investigated the correlation of mTOR pathway (PI3K/AKT/mTOR/p70S6K) activity with the loss of balance in T helper 2/regulatory T (Th2/Treg) cells in the peripheral blood of PV patients. CD4+ T cells were isolated from 15 PV patients and 15 healthy controls (HCs), the ratios of Th2/CD4+ T cells and Treg/CD4+ T cells, the activity of the mTOR pathway (PI3K/AKT/mTOR/p70S6K), the transcription factors and cytokines of Th2 and Treg cells were detected. Primary CD4+ T cells from PV patients were cultured under Th2- or Treg-polarizing conditions with or without rapamycin in vitro. We found that PV patients showed significantly elevated serum IL-4 when compared with HCs, and serum IL-4 level was positively correlated with the titer of anti-Dsg1/3 antibody and disease severity, while the serum TGF-β level was negatively correlated with the titer of anti-Dsg3 antibody and disease severity. Meanwhile, PV patients showed increased Th2/CD4+ T cell ratio; decreased Treg/CD4+ T cell ratio; elevated mRNA of PI3K, AKT, mTOR and protein of PI3K (P85), AKT, p-AKT (Ser473), mTOR, p-mTOR (Ser2448), p-p70S6K (Thr389), GATA3; reduced protein of forkhead box protein 3. Rapamycin inhibited Th2 cell differentiation and promoted Treg cell differentiation in vitro. These data suggest a close association between mTOR pathway activation and the loss of balance in Th2/Treg cells in peripheral blood of PV patients. Inhibiting mTORC1 can help restore the Th2/Treg balance.

Background New therapeutics are urgently needed for infectious diseases, especially for the fungal infection like Fonsecaea monophora. Photodynamic therapy has been showing antimicrobial activity on some pathogens. The combination of antimicrobial medicines and photodynamic therapy (PDT) might be a practical approach. However, whether the treatment of PDT could do benefits to the host immunity remains poorly documented. Results In this study, Galleria mellonella larvae were employed as a model organism to evaluate the activity of PDT, and also to investigate the regulation of humoral immunity by PDT. Photosensitizer 5-aminolevulinic acid (ALA) was applied to the G. mellonella infection model. It was found that ALA-mediated PDT was non-toxic to G. mellonella, and could extend the median survival of infected larvae from 3 days to 5.5 days. We observed that larval hemocytes inhibited the growth of Candida albicans and Staphylococcus aureus, without any contribution by ALA-PDT. Furthermore, the application of ALA-PDT demonstrated the immunomodulation of larval innate immunity as increased hemocyte density counting, cell morphological transformation, and sensitivity to pathogens. Conclusions G. mellonella could be considered as a useful model to study the immunoregulation of PDT. This model revealed that ALA-PDT positively defense against infections through inducing humoral immune responses of larvae.

This report describes a PTCH1 c.1804C > T (p.Arg602*) mutation causing a Chinese nevoid basal cell carcinoma syndrome (NBCCS) with multiple basal cell carcinoma (BCC) phenotype. Multiple modalities including microwave ablation, photodynamic therapy, and excision surgery have a good respond to the NBCCS. The current results broaden the spectrum of PTCH1 mutations responsible for NBCCS.

In the ongoing fight against the epidemic of COVID-19, the medical staff has been under tremendous pressure. Wearing the protective equipment (masks, goggles, and protective screens) with a poor breathability for a long time causes various skin problems, such as allergies, excessive skin hydration, local mechanical injuries, and even secondary infections. In addition, in a closed environment, compression and friction aggravate skin reactions, which may compromise duty performance of the medical staff. It is therefore essential to provide timely treatment opinions and prevention methods for common skin problems. We also give suggestions concerning the preparation of medical kit for skin protection in the epidemic area.

Cutibacterium acnes is capable of inducing inflammation in acne and can lead to a chronic prostatic infection. The diverse pathogenicity among different strains of C. acnes has been presented, but simple appropriate animal models for the evaluation of this bacterium are lacking. In this study, the nematode Caenorhabditis elegans was used as an invertebrate infection model. We revealed that C. acnes type strain ATCC 6919 caused lethal infections to C. elegans in solid and liquid culture media (p

Melanoma is the most lethal skin cancer caused by the malignant transformation of epidermal melanocytes. Recent progress in targeted therapy and immunotherapy has significantly improved the treatment outcome, but the survival of patients with advanced melanoma remains suboptimal. Ferroptosis, a cell death modality triggered by iron-dependent lipid peroxidation, reportedly participates in cancer pathogenesis and can mediate the effect of anti-PD-1 immunotherapy in melanoma. However, the detailed regulatory mechanism of ferroptosis remains far from being understood. In this study, we report that CAMKK2 defines the ferroptosis sensitivity of melanoma cells by regulating the AMPK‒NRF2 pathway. We first found that CAMKK2 was prominently activated in ferroptosis. Then we proved that CAMKK2 negatively regulated ferroptosis through the activation of NRF2 and the suppression of lipid peroxidation. Subsequent mechanistic studies revealed that AMPK connected CAMKK2 upregulation to NRF2-dependent antioxidative machinery in ferroptosis. In addition, the suppression of CAMKK2 increased the efficacy of ferroptosis inducer and anti-PD-1 immunotherapy in the preclinical xenograft tumor model by inhibiting the AMPK‒NRF2 pathway and promoting ferroptosis. Taken together, CAMKK2 plays a protective role in ferroptosis by activating the AMPK‒NRF2 pathway. Targeting CAMKK2 could be a potential approach to increase the efficacy of ferroptosis inducers and immunotherapy for melanoma treatment.

Retraction of ‘SNHG5 promotes proliferation and induces apoptosis in melanoma by sponging miR-155’ by Lu Yan et al., RSC Adv., 2018, 8, 6160–6168, https://doi.org/10.1039/C7RA12520H.

Human papillomavirus (HPV) is the most common sexually transmitted agent in the world. It can cause condyloma acuminatum, anogenital malignancies, and head and neck cancers. The host immune responses to HPV involve multiple cell types that have regulatory functions, and HPV-mediated changes to regulatory T cells (Tregs) in both the local lesion tissues and the circulatory system of patients have received considerable attention. The role of Tregs in HPV infections ranges from suppression of effector T cell (Teff) responses to protection of tissues from immune-mediated injury in different anatomic subsites. In this review, we explore the influence of Tregs in the immunopathology of HPV-related diseases and therapies targeting Tregs as novel approaches against HPV.

Background Anal canal condyloma acuminata are common, sexually transmitted lesions, most often caused by the human papillomavirus. The relatively high recurrence rate of anal canal condyloma acuminata can be attributed to the unsuccessful elimination of viruses in areas of subclinical and latent infection. This study aimed to observe and evaluate the effectiveness of 5-aminolevulinic acid-photodynamic therapy combined with monitoring of human papillomavirus load changes in patients with anal canal condyloma acuminata. Methods A total of 19 patients with anal genital warts were recruited for this study. Firstly, visible warts around the anus were removed. Next, an anoscope examination was performed. Human papillomavirus detection, using real-time polymerase chain reaction assays, was performed before every cycle of treatment. Absorbent cotton rolls soaked with a concentration of 20% 5-aminolevulinic acid were inserted into the anus for 3 h. Finally, photodynamic therapy was applied to the lesions. Each patient required multiple PDT sessions to achieve complete response. Results All patients achieved complete clinical remission one week after the last session of treatment, and human papillomavirus loads decreased significantly. Six months follow-up after completion of therapy, none of the patients had recurrence. Conclusions 5-aminolevulinic acid-photodynamic therapy is an effective and safe approach for anal canal condyloma acuminata. Dynamic human papillomavirus viral quantitative monitoring can aid in the evaluation of therapeutic effects and lead to better treatment outcomes.

This study aimed to investigate the value of miR-222 in hypertrophic scars (HS). Specific mechanisms were used to measure the level of miR-222, while MTT assay, flow cytometry, western blot and qRT-PCR were employed to detect the relative proteins after fibroblasts were transfected with the miR-222 mimic/inhibitor. The direct target of miR-222 was determined by Dual-Luciferase Reporter assay. Furthermore, qRT-PCR and western blot were employed to detect the matrix metalloproteinase 1 (MMP1) RNA/protein after fibroblasts were transfected with the miR-222 mimic/inhibitor. These results revealed that miR-222 was significantly upregulated in HS fibroblasts. The overexpression of miR-222 enhanced the HS fibroblast proliferation, increased the cell population in the S phase, inhibited the cell apoptosis, enhanced the expression levels of Col1A1, Col3A1 mRNA/protein, proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin E1 and CDK1 and reduced the expression levels of cleaved caspase-3/9. However, the miR-222 suppression triggered opposite effects. Furthermore, miR-222 played a regulatory role in HS by negatively regulating its target gene MMP1 by binding with its 3'-untranslated region. The overexpression of MMP1 reduced the expression levels of PCNA and cyclin D1, but enhanced the expression levels of cleaved caspase-3. Therefore, MiR-222 and MMP1 have potential value for HS. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Methods Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. Results HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Conclusions Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV.

Background: Melanoma is the most common malignancy of skin cancer. Small nucleolar RNA host gene 5 (SNHG5), a long non-coding RNA (lncRNA), has been demonstrated to be abnormally expressed in multiple malignances. However, the roles and molecular mechanisms of SNHG5 in melanoma progression have not been well identified. Methods: RT-qPCR assays were used to detect the expression patterns of SNHG5 and microRNA-155 (miR-155). Cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. Cell apoptosis rate was measured by flow cytometry via double-staining of fluorescein isothiocyanate (FITC)-labeled annexin V (Annexin V-FITC) and propidium iodide (PI). The interaction between SNHG5 and miR-155 was validated using bioinformatics analysis, subcellular fraction assay, luciferase assay and RNA immunoprecipitation (RIP) assay. A mouse model of melanoma was established to further verify the effect of SNHG5 on tumor growth in vivo. Results: SNHG5 expression was upregulated in melanoma tumor tissues and cell lines. Moreover, higher SNHG5 expression was associated with advanced pathogenic status and poor prognosis. Functional analysis showed that SNHG5 knockdown suppressed proliferation and facilitated apoptosis in melanoma cells. Mechanical exploration revealed that SNHG5 acted as a molecular sponge of miR-155 in melanoma cells. Restoration experiments delineated that miR-155 down-regulation partly abrogated SNHG5-knockdown-mediated anti-proliferation and pro-apoptosis effect in melanoma cells. In vivo assays further demonstrated that SNHG5 depletion hindered tumor growth through up-regulating miR-155 expression. Conclusion: SNHG5 promoted the development of melanoma by sponging miR-155 in vitro and in vivo, implying the important implication of lncRNAs in melanoma progression and providing a potential therapeutic target for melanoma.

Green efficiency of water resources (WGE) is the basis for developing cleaner production and implementing sustainable development. This study deconstructs WGE into the components of green efficiency identified as agricultural water (AGE), industrial water (IGE), domestic service water (SGE), and ecological water (EGE), then analyzes the dynamic change trend, spatial-temporal evolution characteristics and spatial convergence of identified WGE in Northwest China utilizing the Super-SBM model, spatial convergence model together with an exploration spatial data analysis. The results show that the average of SGE and its average annual growth after 2007 are the highest; Not only do AGE, IGE, SGE, and EGE have obvious spatial-temporal heterogeneity, they will eventually converge into one steady-state growth trajectory at different rates (about 3.8, 3.30, 3.25 and 3.20), which are related to the level of economic development, population size, industrial structure, government expenditure and spatial spillover effects from joining or adjacent areas. In addition to selectively improving some external conditions to promote the path of steady growth of water resources, local governments in Northwest China can also explore the construction of cooperative management and restriction mechanisms on cross-regional water resources to build a “destiny community” for WGE.

Background Multiple human papillomavirus infections are commonly encountered in genital warts. Infection can be eliminated using 5-aminolevulinic acid-based photodynamic therapy. The aim of this study was to identify the preponderant genotypes and patterns of human papillomavirus co-infection clearance during photodynamic therapy in patients with genital warts. Methods We conducted a retrospective study between January 2020 and February 2021 at two hospitals in Guangzhou, China. Human papillomavirus typing and quantitative detection were performed before starting treatment and after each session of photodynamic therapy. Results A total of 97 patients participated in the study. Co-infections with low-risk and high-risk types were common in genital warts. Types 6 was the most common type detected, followed by types 52, 11, 58, 51 and 56. Patients with multiple infections were more likely to have high-risk human papillomavirus infection. The viral load of high-risk human papillomavirus before treatment was significantly lower than that of low-risk human papillomavirus, and decreased faster during therapy. In addition, high-risk types were cleared more readily than low-risk types, and 51.4% of high-risk types were eliminated after three rounds of therapy. A transient increase in viral load, especially low-risk types, was observed after two sessions of therapy. Conclusions Low-risk human papillomavirus was preponderant in patients co-infected with low-risk and high-risk types. Photodynamic therapy effectively eliminated multiple human papillomavirus infections. The response to photodynamic therapy was mainly determined by the low-risk types in patients infected with combinations of low-risk and high-risk types.

IL-33 is a newly discovered member of the IL-1 family and has been identified as a potent inducer of Th2 type immunity. Emerging evidence imply that IL-33 may also act as an alarm to alert the immune system when released by epithelial barrier tissues during trauma or infection. In this study, we further investigate the potential efficacy of IL-33 on dermal wound healing in streptozotocin-induced diabetic mice. A full-thickness skin wound was generated on the back of diabetic mice and treated with IL-33 or vehicle topically. Our data showed that IL-33 delivery contributed to diabetic wound closure with wounds gaping narrower and exhibiting elevated re-epithelialization. IL-33 promoted the new extracellular matrix (ECM) deposition and angiogenesis formation, which indicates an important role of IL-33 on matrix synthesis and neovascularization. Meanwhile, IL-33 accelerated the development of M2 macrophages in wound sites in vivo, and amplified IL-13-induced polarization of bone marrow-derived macrophages toward a M2 phenotype in vitro. Furthermore, IL-33-amplified M2 macrophages augmented the proliferation of fibroblasts and ECM deposition. All together, these results strongly suggest manipulation of IL-33-mediated signal might be a potential therapeutic approach for diabetic skin wounds.

Pemphigus is an autoimmune disease that causes blisters and erosions in the skin and mucous membranes. The development of pemphigus is associated with the imbalance of T-cell and humoral responses. MicroRNAs (miRNAs) can regulate many cell functions. However, whether miRNA expression is altered in peripheral blood mononuclear cells (PBMCs) during the pathogenesis of pemphigus has not been clarified. The aim of the present study was to examine the miRNA expression profiles of PBMCs from patients with pemphigus. The expression profiles of miRNAs in PBMCs from patients with active pemphigus (n=3) and healthy subjects (n=3) were analyzed by microarray. The relative levels of miR-424-5p expression in PBMCs from 9 patients and controls were validated by RT-qPCR. The functional and biological processes of the differentially expressed miRNAs were analyzed by bioinformatics. There were 124 differentially expressed miRNAs in PBMCs from the patients with pemphigus, compared with healthy controls, including 71 that were upregulated (P2), and 53 that were downregulated (P

We performed a meta-analysis to identify the association between systemic lupus erythematosus (SLE) and preterm birth. In this study, we studied the effects of SLE, SLE disease activity, a history of nephritis and active nephritis on preterm birth. Searches were conducted before 20 May 2016 of PubMed, Embase, Medline and Cochrane Library of literature and article reference lists. Eleven observational case–control studies and thirteen cohort studies met the inclusion criteria. The pooled relative risk (RR) for the risk of preterm birth in SLE patients versus controls was 2.05 (95% confidence interval (CI): 1.72–3.32); for active SLE patients versus inactive was 2.98 (95% CI: 2.32–3.83); for SLE patients with a history of lupus nephritis versus those without nephritis it was 1.62 (95% CI: 1.35–1.95); and for SLE patients with active nephritis versus those with quiescent nephritis it was 1.78 (95% CI: 1.17–2.70). In summary, this study identified a significant association in the above results. This association was more significant in active SLE patients versus inactive. With respect to SLE itself, active inflammation (such as disease activity) may be more hazardous for the management of the pregnancy. This suggests that it is essential to control disease activity in order to achieve a better outcome of SLE pregnancy.

Genital HPV infections are widely prevalent. HPV can persist and be transmitted to partners even after warts are gone. The HPV genotype and viral load assay can reveal whether infections are persistent or latent, and it can serve as a predictor of infection clearance. Although numerous studies have demonstrated that photodynamic therapy (PDT) is effective against condyloma acuminata, there is no data on its effects on latent, persistent infections.A total of 20 patients with latent or subclinical HPV infection were evaluated. At each patient visit, polymerase chain reaction was used to identify HPV genotypes and measure the viral loads, which reflect the status of HPV infection. We administered 5-aminolevulinic acid (ALA)-based PDT weekly for patients with active infections, while no treatment was administered to patients with regressing infections.PDT treatment can effectively eliminate HPV, significantly reducing viral loads after three rounds of treatment (p 0.001). The rate of negative HPV DNA test results was higher in patients with latent or subclinical infections than in patients with genital warts after one round of PDT treatment.ALA-PDT can effectively eliminate latent or subclinical HPV infections. Additionally, our assay for identifying HPV genotypes and viral loads, which reflect the status of HPV infection, can accurately guide ALA-PDT treatment.

Verrucous epidermal nevus (VEN) is a skin disorder that commonly presents at birth; it is characterized by skin-colored to brown verrucous papules in a linear distribution following Blaschko’s lines. Even though it is extremely rare, VEN has been associated with malignant transformation. VEN has been treated by different treatment modalities with varying and frustrating results. We introduce a new type of treatment. The fractional micro-plasma radio-frequency (RF) technology, which uses unipolar RF technology to provoke plasma spars, creating multiple controlled micro-perforations on the skin. Photodynamic therapy (PDT) is a type of technology for disease diagnosis and treatment, in which a photosensitizer gathers within the nidus and kills the diseased cells. In this report, we present a case of VEN that was successfully treated with fractional micro-plasma RF technology and PDT without side effects or complications; a follow-up was conducted after 24 months and no signs of recurrence were observed.

Bowenoid papulosis is a polymorphic papular disease that occurs on the external genital area. We investigated the efficacy of 5-aminolevulinic acid-mediated photodynamic therapyin the treatment of Bowenoid papulosis.We investigated 200 Bowenoid papulosis cases from the Department of Dermatology and Venereology of Nanfang Hospital in 2016-2018. Biopsies were performed from Bowenoid papulosis lesions before treatment. The patients were divided into two groups: 100 patients each in the 5-aminolevulinic acid-mediated photodynamic therapy and control groups(radiofrequency cauterisation, microwave ablation, and surgical resection groups). Differences in lesion clearance, recurrence rate, and patient satisfaction after treatment were evaluated.Photodynamic therapy sessions for multifocal Bowenoid papulosis were more frequent than those for monofocal lesions. All lesions in the 5-aminolevulinic acid-mediated photodynamic therapy group were cleared after photodynamic therapy, with no recurrence at the 1-year follow-up; however, 20 (20.0 %) patients in the control showed recurrence after 1 year. Only 5patients in the photodynamic group were unsatisfied with the treatment cost and 34 patients in the control group experienced short-term pain and scarring. The recurrence rate was significantly lower (P 0.05) and patient satisfaction was higher (P 0.05) in the 5-aminolevulinic acid-mediated photodynamic therapy group than those in the control. The recurrence rate was significantly lower (P 0.05) and patient satisfaction was higher (P 0.05) in the 5-aminolevulinic acid-mediated photodynamic therapy group than those in the surgical resection group. The recurrence rate of lesions was significantly lower in the surgical resection group than that in the rest of the control group (P 0.05). There was no difference in recurrence rate and patient satisfaction between the radiofrequency cauterisation and microwave ablation groups.5-aminolevulinic acid-mediated photodynamic therapy for Bowenoid papulosis results in a low recurrence rate and high satisfaction.

Background Condyloma acuminata is a common sexually transmitted disease for which an underlying chronic human papillomavirus (HPV) infection is an important cause of recurrence. 5-aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) has become an effective method to treat condyloma acuminata. Urinary tract condyloma acuminata are not considered common, but warts in the bladder can be detected by cystoscopy. Objective To treat a urinary tract HPV infection in a 35 years old woman diagnosed with condyloma acuminata and to eliminate HPV infection. Method A total of six sessions of ALA-PDT to the cervix and seven sessions of ALA-PDT to the vagina were executed, and the patient subsequently had a cystoscope examination. The wart in the bladder was found by cystoscopy and cauterized with radiofrequency. Result Internal urethra, urethral orifice, cervical, vaginal, and vulvar HPV-DNA detection eventually all returned negative results, and there was no recurrence with two years of follow-up.

Background Aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) is used to treat condyloma acuminata (CA), yielding a high clearance rate and low recurrence rate. Consecutive human papillomavirus (HPV) DNA detection can be used to dynamically monitor the therapeutic efficiency of PDT. Here, we evaluated the efficacy of ALA-PDT in the context of different HPV infection states. Methods One hundred thirty-eight patients with HPV infection and visible anogenital warts were enrolled. Microwave or radiofrequency was used to remove visible lesions before PDT. HPV DNA detection was performed using real-time polymerase chain reaction before each PDT session and at follow-up. Treatment was halted after the patient showed two negative results for HPV DNA detection in a row. Results Of the 138 patients enrolled in the study, 72 completed treatment. Multisite HPV-infected patients required more sessions of PDT than did single-site infected patients to reach the endpoint of treatment. Compared with patients with only external CA, individuals with internal CA required more sessions to eliminate HPV infection. The total number of PDT sessions performed in the multitype HPV-infected group was significantly higher than that in the single-type infected group. Patients with non-high-risk (HR)-HPV infection required fewer PDT sessions than did those with HR-HPV infection by the end of treatment. Sixty-nine patients were followed-up for at least 6 months, only 2.9% of whom showed recurrence. Conclusions Combined ALA-PDT and HPV DNA detection was an effective strategy for the treatment of CA. Patients with multisite and multitype HPV infection required more PDT sessions to eliminate the virus.

Patients with type 2 diabetes mellitus (T2DM) have a very high risk of cardiovascular related events, and reducing complications is an important evaluation criterion of efficacy and safety of hypoglycemic drugs. Previous studies have shown that the dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP4i), such as sitagliptin, might reduce the incidence of major cardiovascular events (MACEs). However, the safety and efficacy of sitagliptin remains controversial, especially the safety for cardiovascular related events. Here, a systematic review was conducted to assess the cardiovascular safety of sitagliptin in T2DM patients. The literature research dating up to October 2018 was performed in the electronic database. The clinical trials about sitagliptin for T2DM patients were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria. The primary outcome was the MACE, and the secondary outcome was all-cause mortality. Finally, 32 clinical trials composed of 16082 T2DM patients were included in this meta-analysis. The results showed that: there was no significant difference between sitagliptin group and the control group on MACE (odds ratio (OR) = 0.85, 95% confidence intervals (CIs) = 0.63–1.15), myocardial infarction (MI) (OR = 0.66, 95% CI = 0.38–1.16), stroke (OR = 0.83, 95% CI = 0.44–1.54) and mortality (OR = 0.52, 95% CI = 0.26–1.07). These results demonstrated that sitagliptin did not increase the risk of cardiovascular events in patients with T2DM.

Background Erythrokeratodermia variabilis et progressiva (EKVP, OMIM 133200) is a rare hereditary disorder characterized by varies from transient, fast moving erythema to persistent brown hyperkeratotic plaques. Recently, mutations in the genes gap junction alpha 1 gene (GJA1), GJB3, and GJB4 have been reported to cause EKVP. Here, we report the identification of two de novo missense mutations in the GJA1 gene in two unrelated individuals with EKVP. Methods The patients and his family members were subjected to mutation detection in the candidate gene GJA1, GJB3, and GJB4 by Sanger sequencing. The expression of connexin (Cx) 43 was detected by immunohistochemistry and immunofluorescence (IF) studies in the lesions. Results A 12‐year‐old boy presented with multiple hyperkeratotic plaques on the face, neck, elbows, wrists, limbs, knees, inguinal region, hands, and feet. A 7‐year‐old girl presented with symmetrical erythematous, plaques on the hands, feet, wrists, and ankles. A novel heterozygous missense mutation c.848C > T (p.P283L) in exon 2 of the GJA1 gene was identified in both patients. A novel heterozygous missense mutation c.869C > A (p.T290N) in exon 2 of the GJA1 gene was also identified in the boy. These mutations were not found in the unaffected family members and 100 normal controls. In the patients’ lesions, Cx43 protein was located to the cytomembrane and cytoplasm in the stratum corneum, and granular layer. Compound heterozygous mutations in the boy showed a more severe clinical phenotype and cytoplasmic mislocalization. Conclusions The novel mutations c.848C > T (p.P283L) and c.869C > A(p.T290N) arose de novo and were considered as the cause of two Chinese EKVP. GJA1 P283L and T290N mutations lead to Cx43 protein cytoplasmic mislocalization. Our finding expands the mutant spectrum of GJA1 gene and adds new understanding of the genotype‐phenotype correlation.

Background Epidermolytic palmoplantar keratoderma (EPPK) is a rare skin disorder and its pathogenesis and inheritability are unknown. Objective To investigate the inheritance and pathogenesis of EPPK. Methods Two EPPK cases occurred in a three‐generation Chinese family. Patient–parents trio EPPK was carried out and the identified candidate variants were confirmed by Sanger sequencing. Results A heterozygous missense pathogenic variant, c.488G > A (p.Arg163Gln), in the keratin (KRT) 9 gene was detected in the proband and his son via targeted exome sequencing, and then validated by Sanger sequencing. This pathogenic variant cosegregated with the EPPK in extended family members, and was predicted to be pathogenic by SIFT, PolyPhen2, PROVEAN, and Mutation Taster. This heterozygous variation was not evident in 100 healthy controls. Conclusion This report describes a KRT9 c.488G > A (p.Arg163Gln) variant causing a diffuse phenotype of Chinese EPPK. The current results broaden the spectrum of KRT9 pathogenic variants responsible for EPPK and have important implications for molecular diagnosis, treatment, and genetic counseling for this family.

Mesenchymal stem cells (MSCs) pretreatment is an effective route for improving cell-based therapy of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that the application of human umbilical cord-MSCs (hUC-MSCs) pretreated with angiotensin-II (Ang-II) might be a potential therapeutic approach for severe acute pancreatitis (SAP). Therefore, the effect of Ang-II pretreated hUC-MSCs on SAP was investigated in vitro and in vivo. Methods In the present study, human umbilical cord-derived MSCs pretreated with or without Ang-II were delivered through the tail vein of rats 12 h after induction of SAP. Pancreatitis severity scores and serum lipase levels, as well as the levels of VEGF and VEGFR2 were evaluated. Results We found that the administration of Ang-II-MSCs significantly inhibited pancreatic injury, as reflected by reductions of pancreatitis severity scores, serum amylase and serum lipase levels. Furthermore, the reduced apoptotic rate and increased tube formation in human umbilical vein endothelial Cells (HUVEC) were found resulting from the administration of Ang-II-MSC-CM. Moreover, knockdown of VEGFR2 can block the effect of Ang-II-MSC-CM on preventing HUVEC from apoptosis, as well as the capacity of tube formation was also suppressed. In addition, the expression of increased Bcl-2 and alleviated caspase-3 were observed in HUVEC and HUVEC transfectants exposure to Ang-II-MSC-CM. Conclusion Collectively, these results elucidated that the pretreatment of hUC-MSCs with Ang-II improved the outcome of MSC-based therapy for SAP via enhancing angiogenesis and ameliorating endothelial cell dysfunction in a VEGFR2 dependent manner.

Pemphigoid gestationis (PG) is a rare, autoimmune, subepidermal bullous dermatosis associated with pregnancy. It is mainly caused by autoantibodies against hemidesmosomal proteins-bullous pemphigoid 180, and usually presents in the second or third trimester of pregnancy sometimes exacerbates spontaneously after delivery. Here we reported a case of PG with polycystic ovary syndrome (PCOS). This patient received assisted reproduction technology and suffered PG in her third trimester of pregnancy. To the best of our knowledge, there is no similar case has been reported.

To investigate the psychological health and related risk factors in patients suffering from psoriasis. A total of 245 inpatients and outpatients with psoriasis were selected from January 2014 to December 2015. Patients with psoriasis were assessed a homemade questionnaire as well as the Psoriasis Area and Severity Index (PASI), Selfrating Anxiety Scale, Self-rating Depression Scale, Trait Coping Style Questionnaire and Social Avoidance and Distress Scale.Differences in sex, age, marital status, type of medical payment, occupation, economic situation, disease severity, and type of psychological state of psoriasis patients were significant, there was no significant difference in psychological health between psoriasis patients with different levels of educational attainment. Scores for anxiety, depression, social avoidance, and social distress were positively correlated with disease severity and negative-coping scores, but a significant negative correlation was observed with scores for social support and positive coping. Stepwise regression analysis of factors influencing psychological health showed that total social support and negative-coping scores could explain 65.2% of the variation. Patients with psoriasis can suffer from anxiety, depression, social distress, and social avoidance. Physicians should pay greater attention to deterioration in mental health of psoriasis patients.

Chromoblastomycosis is a long-term fungal infection of the skin and subcutaneous tissue, usually presenting as partial hypertrophic and warty plaques. Effective treatment is necessary to control the development of lesions, especially in patients with associated diseases. But till now, the treatment is still a challenge. Photodynamic therapy (PDT) is an efficient and non-invasive treatment option. Here, we reported the case of a 52-year-old male with refractory chromoblastomycosis and leukopenia, who was successfully treated with 5-aminolevulinic acid-based PDT (ALA-PDT). A complete cure, confirmed by clinical improvement and mycological detection, was achieved after six sessions of every-other-week treatment. Post six months follow up no recurrence was observed. The case here suggests that ALA-PDT is a valuable anti-infective therapy for refractory chromoblastomycosis.

Human papillomavirus (HPV) infection is linked to several diseases, the most prominent of which are cervical cancer and genital condyloma acuminatum. Previous studies have suggested an effective role for 5-aminolevulinic acid photodynamic therapy (ALA-PDT) against various cancers by the induction of autophagy and apoptosis. However, few reports have focused on the effectiveness of ALA-PDT on HPV related disorders. To identify the role of ALA-PDT in the context of HPV infection, we initially investigated 111 patients suffering from genital condyloma acuminatum. HPV viral load detected before and after ALA-PDT treatment was compared during this procedure; a significant difference was noted. HeLa (HPV18) cells were exposed to ALA-PDT in vitro to further explore the underlying mechanisms. Western blot analysis showed that ALA-PDT induces LC3II and p62 expression, along with the up regulation of caspase-3 and cleaved caspase-3. Our study also demonstrated that ALA-PDT treatment inhibits the proliferation of HeLa cells in a dose dependent manner and effectively reduces HPV viral load via autophagy and apoptosis by regulating the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways. Hydroxychloroquine (HCQ), although it inhibited autophagy degradation, functioned to activate reactive oxygen species (ROS) levels of ALA-PDT to enhance the observed effect. These findings suggest strategies for the improvement of PDT efficacy in patients.

Jun Gao,1,2 Kang Zeng,1 Yi Liu,3 Lin Gao,4 Lishi Liu1 1Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 2Department of Dermatology, Liuzhou Worker’s Hospital, Liuzhou, China; 3Department of Hand and Foot Surgery, Liuzhou Worker’s Hospital, Liuzhou, China; 4Department of Clinical Medical Research Center, The 2nd Clinical Medicine College (Shenzhen People’s Hospital) of Jinan University, Shenzhen, China Introduction: Melanoma has been reported as the most common malignancy in skin cancer. The small nucleolar RNA host gene 5 (SNHG5), an lncRNA, has been proven as a vital regulator in several types of carcinoma. This study was designed to investigate the detailed roles and possible mechanisms of SNHG5 in melanoma progression. Methods: Quantitative real-time PCR (qRT-PCR) analysis was conducted to detect the expression levels of SNHG5, miR-26a-5p and transient receptor potential, canonical 3 (TRPC3) mRNA in melanoma tissues and cells. CCK-8 assay was used to measure the cell viability. Flow cytometry assays were performed to determine the cell cycle distribution and apoptosis. The invasive ability was assessed by a 24-well Transwell insert. Western blot analysis was employed to evaluate the protein expression of TRPC3. Dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were applied to identify the interactions among SNHG5, miR-26a-5p and TRPC3.Results: The results showed that SNHG5 expression was increased in melanoma tumor tissues and cell lines. Higher SNHG5 expression was correlated with advanced pathogenic status. Moreover, SNHG5 could serve as a molecular sponge of miR-26a-5p. SNHG5 downregulation repressed proliferation, promoted apoptosis, and decreased invasion in melanoma cells, while these effects were greatly counteracted by miR-26a-5p inhibitor. Furthermore, miR-26a-5p directly targeted TRPC3 to suppress its expression, and this effect was aggravated following SNHG5 downregulation. Also, TRPC3 depletion exerted similar tumor-suppressive functions as SNHG5 knockdown. Conclusion: SNHG5 promoted melanoma development by inhibiting miR-26a-5p and facilitating TRPC3 expression, highlighting the potential of SNHG5 as a novel target therapy for melanoma. Keywords: lncRNA, SNHG5, miR-26a-5p, TRPC3, cutaneum carcinoma

Background.Chemokines may be involved in the pathogenesis of urticaria, but their correlation with disease severity as well as eruption type is unclear.Objectives.The aim of this study was to explore the expression of chemokines in patients with urticaria. The association between disease severity and levels of chemokines was analysed.Materials and Methods.Serums CCL11, CCL17, CCL26, and CCL27, D-dimer, C-reactive protein, and total IgE were measured in 51 patients with urticaria and in 25 healthy control subjects.Results.Serums CCL11, CCL17, CCL26, and CCL27 were significantly higher in patients with urticaria than in the healthy controls (P<0.05). Serum CCL27 strongly correlated with urticarial disease severity. Serums CCL17, CCL26, and CCL27 significantly correlated with D-dimer, while innercorrelations were noted among the chemokines.Conclusion.Our findings reveal that chemokines participate in the pathogenesis of urticaria. Further study in larger cohort is needed to testify whether they could be the biomarkers for predicting the severity of urticaria.

Disseminated superficial actinic porokeratosis (DSAP), a genodermatosis transmitted as an autosomal dominant trait featuring disorder of keratinization, is characterized clinically by annular plaques with an atropic center and hyperkeratotic edges.1-4 Recently, Zhang et al. 2 reported MVK mutations in 33% familiar and 16% sporadic patients with DSAP by exome sequencing. Here, we report a single novel mutation of MVK, p.Cys161_Arg176del, in a Chinese family suffering from DSAP. This article is protected by copyright. All rights reserved.

Awareness of the spectrum of clinical manifestations of syphilis, especially uncommon changes, is essential for diagnosis and effective management of patients. A 48-year-old Han businessman presented to the ear, nose and throat surgeons with an eight-week history of epigastric pain, a four-week history of a widespread non-itchy rash including the scrotal skin and a one-week history of tinnitus and dizziness. On examination, he was afebrile with widespread lymphadenopathy and a maculopapular rash affecting his trunk and scrotum. His abdomen was soft but tender in the epigastrium. The Treponema pallidum particle agglutination assay result was positive, and the rapid plasma reagin was 1:2. Gastroscopy showed ulcers in the gastric antrum and pylorus. Histopathological examination of gastric mucosa lesions showed a large amount of lymphoplasmacytic infiltrate detected in the lamina propria of the gastric mucosa. The T. pallidum Liferiver real time polymerase chain reaction kit assay performed on specimens from skin lesions and gastric mucosal tissue were positive. The patient was treated with intravenous sodium penicillin followed by intramuscular benzathine penicillin. On the fourth day of the treatment, the rash, epigastric pain and lymphadenopathy subsided. Two weeks after treatment, the tinnitus alleviated and vertigo disappeared.

Infections with human papillomavirus in the anogenital area result in warty, papillary, and condylomatous lesions. The giant anogenital wart is relatively uncommon. Treatment of giant wart is challenging, especially in the immunosuppressive population. Here, a patient with systemic lupus erythematosis had extensive, fast-growing, recurrent anogenital condylomatosis shaped as giant cauliflowers. We reported this case and the successful treatment of photodynamic therapy combined with surgical management. It provided the feasibility for surgical ablation combined with ALA-PDT performed for these kinds of challenging cases.

Background This study aimed to evaluate the effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the improvement of symptoms and recurrence rate in patients with vulvar lichen sclerosus (VLS) and observe its side effects. Methods The symptom scores before and after photodynamic therapy (PDT) in 13 enrolled patients with VLS were analyzed retrospectively. All patients were followed-up for at least 6 months to evaluate the recurrence rate after PDT. The patients were treated with PDT only during the study period. During the PDT treatment, a 20 % 5-aminolevulinic acid solution was applied to the lesions and marginal areas for 3 h, and the entire area was then irradiated with 635 nm red light of 80 J/cm2 at 80 mW/cm2 for 30 min. Results In this study, the effective rate of PDT was 92.31 %. Lesions recurred in two patients at 6 months after PDT. Post-treatment, the total subjective, total objective, and the Dermatological Life Quality Index scores changed from 11.4, 4.3, and 13.4 at baseline to 4.9, 2, and 5.9, respectively. The difference was statistically significant (p Conclusions ALA-PDT is a safe and effective method for the treatment of VLS, and the therapeutic effects can be maintained for at least 3 months. The therapeutic effects may decrease during the 3–6-month period after PDT.

5-aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) is a highly effective, safe, and promising treatment for human papillomavirus (HPV)-induced anogenital condyloma acuminata (CA). Specific HPV subtypes are responsible for the pathogenesis of CA and dynamic changes in viral loads may reflect the efficiency of PDT. Here we present two cases of anogenital CA successfully treated by ALA-PDT under the guidance of HPV DNA detection including genotype identification and viral load measurement, which provided clues for unexpected intra-anal infection. Both of these male patients were free of detectable HPV at the end of the treatment and no recurrence was observed after 1 year. We conclude that the HPV DNA detection can accurately guide ALA-PDT, indicate unnoticed lesions, as well as improve and evaluate the efficiency.

Objectives: Condyloma acuminatum are the most common sexually transmitted diseases worldwide, and they are closely associated with human papillomavirus (HPV) infection. Urethral meatus is one of the places that warts occur. Many treatments for uretheral warts have limitations. In this study, we performed 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) on patients and investigated the effectiveness of reducing HPV viral loads. Materials and Methods: In our study, 21 patients diagnosed with urethral condyloma acuminatum were included. After 4 h treatment of ALA, patients received PDT. Each patient received HPV test before every PDT cycle. The frequency of PDT was dependent on viral load changes. Results: All patients achieved complete clinical remission after the last session of ALA-PDT. There were significant differences in HPV viral loads between pretherapy and after one or three rounds of PDT treatment. Conclusions: ALA-PDT is a safe and effective method for treatment of condyloma acuminatum in urethra meatus. Dynamic monitoring of HPV viral loads can more objectively demonstrate the effectiveness and guide the treatment of PDT.

Objective: Investigate the role of Yes-associated protein (YAP1) in the development of condyloma acuminatum (CA). Methods: We enrolled 30 male patients with CA and 20 healthy individuals as a control group, to compare the YAP1 expression in their tissue samples. Following this, we overexpressed and downregulated YAP1 expression in HaCaT cells to examine the migratory, proliferative, and apoptotic potential of HaCaT cells expressing different levels of YAP1. Results: In the CA patient tissue samples, an increase in YAP1 expression can be observed. In vitro,the overexpression of YAP1 was shown to promote the growth and migration of HaCaT cells and to activate epidermal growth factor receptor (EGFR) pathway-associated proteins, while the downregulation of YAP1 inhibited cell growth and migration of these cells. Conclusions: YAP1 promotes the growth of keratinocytes in CA through the activation of the EGFR pathway, and it may mediate the development of human papilloma virus-associated diseases.

Background Pemphigus is a common life-threatening, autoimmune bullous disease effecting both cutaneous and mucous membranes. Previous diagnosis of pemphigus is based on clinical presentations, histopathology, immunofluorescence and enzyme-linked immunosorbent assay. Furthermore, no laboratory parameters could be used to indicate disease severity. MicroRNAs are endogenous small RNAs, which could be used as diagnostic biomarkers for some autoimmune diseases. Previously, miR-338-3p has been proven significantly up-regulated in pemphigus patients. Methods Pemphigus patients (including pemphigus vulgaris and pemphigus foliaceus) with active lesions and with remission, patients diagnosed as bullous pemphigoid and healthy volunteers were recruited, and miR-338-3p expression level was measured using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Active pemphigus patients accepting treatment were followed up for at least 2 weeks to investigate the expression change of miR-338-3p during treatment period. Target genes of miR-338-3p were screened through computer-aided algorithm and verified by RT-qPCR, Western blot and Luciferase activity assay. Results MiR-338-3p was specifically increased in patients diagnosed as pemphigus with active lesions. The expression level of miR-338-3p gradually decreased after effective treatment. MiR-338-3p expression was independently correlated with disease severity defined by PDAI (Pemphigus Disease Area Index) or ABSIS (Autoimmune Bullous Skin Disorder Intensity Score) criteria. Up-regulation of miR-338-3p could significantly suppress RNF114 expression at mRNA and protein level in vitro. Discussion MiR-338-3p could be used as a diagnostic biomarker of pemphigus in addition to other traditional methods. Up-regulation of MiR-338-3p was associated with more severe condition in pemphigus. RNF114 is the target gene of miR-338-3p, which probably participates in the regulation of disease activity of pemphigus.

Aim: To study the pathogenesis of chromoblastomycosis using the alternative model host Galleria mellonella. Methodology: We analyzed the virulence of different dematiaceous fungal strains and the host immune responses (hemocytes density and morphological changes) to Fonsecaea monophora by the alternative infection model. Then detected the development of the pathogenic muriform cells within larvae under microscope. Results: Increasing inocula resulted in greater larval mortality and Cladophialophora carrionii was the most virulent. Low inocula activated the humoral immune response significantly. Moreover, the conidia underwent morphological transition to muriform cells within larvae. Conclusion: We developed an invertebrate host model that can be used to evaluate the virulence of dematiaceous fungi, which may provide further insights into overcoming current limitations in studying chromoblastomycosis in vivo.