Dihydroartemisinin suppresses growth of squamous cell carcinoma A431 cells by targeting the Wnt/ß-catenin pathway.

The antimalarial effects of dihydroartemisinin (DHA) have been well documented. However, its potential against skin cancer has not been explored as yet. Therefore, we assessed the function of DHA as an inhibitory factor of squamous cell carcinoma in A431 cells and the underlying mechanism was explored. After stimulation of A431 cells and Hacat cells (normal human keratinocyte cells, as control) with various doses of DHA, the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to assess the proliferation of both cell lines and cell apoptosis was analyzed by flow cytometric analysis. Furthermore, after pretreatment with the Wnt/ß-catenin signaling pathway activator BIO or anti-caspase-3 antibody, mRNA levels of antiapoptotic gene survivin and proapoptotic gene caspease-3 were explored by quantitative real-time PCR, the corresponding protein levels were detected by western blotting, and the proliferation of A431 cells was also analyzed. DHA inhibited the proliferation and viability of A431 cells in a time-dependent and dose-dependent manner and induced cell apoptosis. We also observed decreased surviving expression and increased caspase-3 expression of A431 cells. Furthermore, these effects depended on the suppression of Wnt/ß-catenin signaling as pretreatment with the Wnt activator BIO markedly dampened the DHA-induced effects. More interestingly, when the caspase-3 expression was silenced using an antibody, the DHA-induced growth inhibition of A431 cells was offset significantly. Our results confirm that DHA inhibits skin cancer A431 cells by suppressing Wnt/ß-catenin signaling. Our findings provide a potential target for squamous cell carcinoma treatment.

Quality of life of patients with neurodermatitis.

BACKGROUND: Neurodermatitis is a common chronic skin disease. Although not life-threatening, it can produce an important psychosocial burden, sleep disturbance and sexual dysfunction. Patients with neurodermatitis tend to have poor social skills or interpersonal resources and a lack of flexibility. However quality of life (QoL) of patients with neurodermatitis has seldom investigated. The objective of this study is to assess the impact of neurodermatitis on patients' QoL using the Dermatology Life Quality Index questionnaire, and assess its feasibility and internal consistency. METHODS: One hundred and fifty consecutive outpatients seeking treatment for neurodermatitis and 250 patients with psoriasis in the Department of Dermatology, the Second Hospital of Xi'an Jiaotong University, were assessed for eligibility for this prospective study from July 1, 2011 to September 30, 2011. Demographic data and disease-related characteristics were collected. RESULTS: The overall mean DLQI score for neurodermatits (9.34) was lower than that for psoriasis (13.32) (P < 0.001). Patients with neurodermatitis scored significantly lower for all items except Q1 (symptoms) and Q9 (sexual difficulties). No strong relationship between disease-related characteristics and quality of life could be found. The inter-item correlation averaged 0.415 and Cronbach's alpha was 0.889, indicating high internal consistency. CONCLUSION: This is the first study to attempt to measure the impact of neurodermatitis for both male and female patients on QoL. Neurodermatitis moderately affected the QoL of the patients.

[Expression of integrin beta1 in squamous cell carcinoma].

OBJECTIVE: To study the expression of integrin beta1 in squamous cell carcinoma (SCC) and explore the relationship between stem cell marker and SCC. METHODS: The expressions of integrin beta1 in SCC tissues and SCC cell strain A431 were detected with immunohistochemical methods and cell staining method. The differentiation of SCC cells were induced with all-trans-retinoic acid (ATRA). The changes of integrin beta1 levels before and after induction were detected with RT-PCR. RESULTS: In highly differentiated SCC tissues, integrin beta1 was constantly expressed in the basal-like cells in the edge of tumor; some cells inside arranged as island also showed positive integrin beta1 expression. In poorly differentiated SCC tissues, island-like integrin beta1-positive cells remarkably increased and distributed in a diffuse way. In SCC A431 cells, integrin beta1 was expressed unevenly in tumor cells. After treatment by ATRA, level of integrin beta1 mRNA in A431 cells significantly decreased compared with untreated control (P < 0.05), and the ratios between the intensity values of integrin beta1 to beta-actin were 0.071 +/- 0.025 and 0.029 +/- 0.018 at 24 h and 48 h, respectively, whereas in controls were 0.148 +/- 0.027 and 0.136 +/- 0.011 (P < 0.05). CONCLUSIONS: Integrin beta1 is heterogeneously expressed in both SCC tissues and SCC A431 cells. The expression of Integrin beta1 decreases when the differentiation level of tumor cells increase, indicating that integrin beta1 is closely related with the initiation of SCC and potential cancer stem cells in SCC.

Consensus on Pre-examination and Triage in Clinic of Dermatology During Outbreak of COVID-19 From Chinese Experts.

The 2019 novel coronavirus infection has brought a great challenge in prevention and control of the national epidemic of coronavirus disease 2019 (COVID-19) in China. During the fight against the epidemic of COVID-19, properly carrying out pre-examination and triage for patients with skin lesions and fever has been a practical problem encountered in hospitals for skin diseases as well as clinics of dermatology in general hospitals. Considering that certain skin diseases may have symptom of fever, and some of the carriers of 2019 novel coronavirus and patients with COVID-19 at their early stage may do not present any symptoms of COVID-19, to properly deal with the visitors to clinics of dermatology, the Chinese Society of Dermatology organized experts to formulate the principles and procedures for pre-examination and triage of visitors to clinics of dermatology during the epidemic of COVID-19.

A double-blind, randomized, placebo- and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis.

BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.

[Mutation detection of ATP2C1 gene in Chinese patients with Hailey-Hailey disease].

OBJECTIVE: To investigate the mutations of ATP2C1 gene in Chinese patients with Hailey-Hailey disease (HHD). METHODS: Genomic DNA was extracted from peripheral blood leukocytes. PCR and direct DNA sequencing were used to detect the mutations in all 27 exons of ATP2C1 gene in patients of two Chinese families and a sporadic patient with HHD. RESULTS: Three mutations in ATP2C1 gene were found, including 1 nonsense mutation, 1 deletion/frameshift mutation and 1 missense mutation. All of them were novel mutations. CONCLUSION: All the three mutations could affect the transcription and translation, and further the function of protein encoded by ATP2C1 gene.

The synergy of diammonium glycyrrhizinate remarkably reduces the toxicity of oxymatrine in ICR mice.

Most traditional Chinese medicine prescription dosages are imprecise. This study analyzes the toxicities and adverse effects of a combination the active ingredients of licorice and Kushen medicine: oxymatrine (OMT) and diammonium glycyrrhizinate (DG). The median lethal dose (LD50) and mortality were analyzed in single-dose OMT (or DG) intraperitoneally injected mice with or without combination DG (or OMT). Body weight changes as well as levels of serum sodium and potassium, alanine transaminase (ALT), aspartate transaminase (AST), creatinine, and urea were measured in mice treated with a daily dose of OMT and/or DG for 14days. This study showed that the LD50 of OMT for males and females were 347.44 and 429.15mg/kg, respectively. The LD50 of DG were 525.10 and 997.26mg/kg for males and females, respectively. DG significantly decreased the mice LD50-induced mortality of the OMT, however OMT did not succeed in reducing the LD50-induced mortality rate of DG. The combination of OMT and DG obviously attenuated the changes of the body weight, serum sodium, and potassium induced by DG or OMT alone. These results suggested that toxicity and adverse effects of the OMT was significantly attenuated by DG. The OMT neutralized the adverse effects of the DG, but not the toxicity.

Novel Splice-Site Mutation of KRT1 Underlies Diffuse Palmoplantar Keratoderma in a Large Chinese Pedigree.

AIMS: To identify potential causative gene mutations in a large Han Chinese pedigree with diffuse nonepidermolytic palmoplantar keratoderma (NEPPK). METHODS: We enrolled 11 patients and 8 healthy individuals from a pedigree with NEPPK and 100 randomly selected healthy controls. Biopsy samples were obtained from the proband. Genomic DNA was extracted from a peripheral blood sample from each participant. Mutation detection via polymerase chain reaction and Sanger sequencing of relevant potential causative genes, including KRT1, KRT6C, KRT10, KRT16, AQP5, and SERPINB7, was performed. Comparisons were made between sequencing outcomes and currently available reference genome databases, including HGMD Pro, Pubmed, 1000 Genomics, and dbSNP. RESULTS: Histological findings, clinical features, and medical history were in accordance with the diagnosis of diffuse NEPPK. We identified a novel splice-site mutation c.1255-1G > C in intron 6 of KRT1 in all individuals with NEPPK in the pedigree. CONCLUSIONS: Diffuse NEPPK is a relatively rare subtype of palmoplantar keratoderma. The results of this study expand the spectrum of KRT1 mutations in diffuse NEPPK and provide insights into the understanding of its underlying pathological mechanisms and phenotype-genotype correlations.

Eight Novel Mutations of the ADAR1 Gene in Chinese Patients with Dyschromatosis Symmetrica Hereditaria.

AIMS: To identify potential novel gene mutations in Chinese patients with dyschromatosis symmetrica hereditaria (DSH). METHODS: We enrolled 8 Chinese patients with familial DSH, 5 Chinese patients with sporadic DSH, and 100 randomly selected healthy individuals in this study. The genome of each participant was extracted from peripheral blood samples. Sanger sequencing of the ADAR1 gene was performed after polymerase chain reaction amplifications. Comparisons between the DNA sequences of the affected individuals and the NCBI database were performed. RESULTS: We detected eight novel heterozygous mutations and five previously reported mutations in the ADAR1 gene in our patients. The novel mutations include c.1934 + 3A>G, c.2749A>G, c.2311insA, c.3233G>A, c.3019 + 1G>T, c.2894C>A, c.1202_1205del, and c.2280C>A. These detected novel mutations are predicted to induce two frame-shift mutations, one nonsense mutation, three missense mutations, and two splice-site mutations. CONCLUSIONS: The findings of this study expand our knowledge of the range of ADAR1 gene mutations in DSH and will contribute to identifying correlations between the various DSH phenotypes and genotypes. Furthermore, they may provide insight into the underlying pathogenic mechanism.

The progression of CD56+ myeloid sarcoma: A case report and literature review.

The current study presents a case of cluster of differentiation (CD)56+ myeloid sarcoma in a patient that initially presented with skin lesions, and provides evidence for the clinical and differential diagnosis of myeloid sarcoma. The patient of the present case report was a 65-year-old man who was admitted to hospital with a six-month history of bilateral purple-red papules and nodules, which were present on the upper limbs of the patient and had spread over his whole body one month prior to admission to the hospital. Pathological examination demonstrated a diffuse infusion of primitive round cells at the papillary dermis and subcutaneous tissues. The infiltrated cells were 40-60 µm in diameter and morphologically identical. Immunohistochemical examination revealed that the cells expressed myeloperoxidase, CD56, CD43 and T-cell intracytoplasmic antigen. In addition, several cells expressed CD34, and 90% of the cells expressed Ki67. While the majority of cells in myeloid sarcoma do not express CD56, the present case was a myeloid sarcoma that expressed CD56, which is extremely rare. The sarcoma in the present patient progressed rapidly, and the patient died eight months following the onset of disease. Clinicians should be aware of CD56+ myeloid sarcoma, which is easily misdiagnosed and inappropriately treated. Consequently, myeloid sarcoma may have a high malignancy and poor outcome for patients.

[Investigation of steroid sulfatase gene in two pedigrees with X-linked ichthyosis].

OBJECTIVE: To investigate the gene mutation in two pedigrees with X-linked ichthyosis (XLI) and explore the relationship between the mutation and clinical manifestations. METHODS: Genomic DNA of the affected and normal members of the pedigrees and 50 unrelated normal subjects from different regions was extracted with a whole blood genomic DNA extraction kit for use of the template for PCR amplification of exon 1, exon 2 and exon 10 of the steroid sulfatase (STS) gene. RESULTS: The STS gene was partially deleted in the affected members in the pedigrees with XLI, leaving only exon 1 but not the other exons. The normal member of the pedigree and 50 unrelated normal subjects had no such deletion. CONCLUSION: Partial deletion of the STS gene exists in the two pedigrees with XLI, which is responsible for pathological skin changes characteristic of XLI.

Blastic plasmacytoid dendritic cell neoplasm: A case report.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN), formerly known as agranular cluster of differentiation (CD)4+/CD56+ hematodermic neoplasm, is a rare and aggressive type of lymphoma, with only ~100 cases reported worldwide. BPDCN is a hematological malignancy derived from precursors of plasmacytoid dendritic cells and is clinically characterized by cutaneous manifestations involving the lymph nodes and peripheral blood, a leukemia-like dissemination and a poor prognosis. The present study reports the case of a 54-year-old male who presented with symptoms characteristic of BPDCN. Pathological and immunohistochemical analysis of abdominal skin lesion biopsies were used to determine a diagnosis of stage IIIE BPDCN. Although cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy was administered, the patient succumbed to BPDCN nine days after the discontinuation of chemotherapy. Thus, the period from BPDCN presentation to mortality was ≤3 months. The case reported in the present study was characterized by rapid development and poor prognosis, and displayed additional features of BPDCN, including systemic dissemination and a short survival period.

A novel mutation in the second half of the keratin 17 1A domain in a large pedigree with delayed-onset pachyonychia congenita type 2.

Pachyonychia congenita type 2 (PC-2), also known as Jackson-Lawler type PC, is an autosomal dominant disorder characterized by hypertrophic nail dystrophy associated with focal keratoderma and multiple pilosebaceous cysts. We report a large Chinese pedigree of typical delayed-onset PC-2 that includes 19 affected members. Direct sequencing of PCR products revealed a novel heterozygous 325A-->G mutation in the affected members. This mutation predicts the substitution of asparagine by aspartic acid in codon 109 (N109D) located in the second half of the keratin 17 1A domain, where similar mutation in keratin 5 is associated with the mild Weber-Cockayne form of epidermolysis bullosa simplex.

Transcriptional activation function of hepatitis B virus Pre S1 protein in yeast.

OBJECTIVE: To explore the feasibility of cloning of the hepatocyte receptor interacting with the Pre S1 protein of HBV by two-hybrid system. METHODS: Yeast expression plasmids encoding fusion proteins of full length or portions of Pre S1 of HBV and DNA binding domain of yeast protein GAL4 were constructed and used to transform yeast reporter strain SFY526. Reporter gene product beta-galactosidase activity was assayed as a measure of transcriptional activation in yeast. Mammalian expression plasmid encoding fusion proteins of full length Pre S1 and DNA binding domain of GAL4 was constructed and used to cotransfect hepatoma cell line Huh-7 together with CAT reporter plasmid. Cell extracts were assayed for CAT activity by thin-layer chromatography. RESULTS: The fusion proteins of full length Pre S1 protein and GAL4 DNA binding domain presented transcriptional activation function in yeast. The transcription activating sequence was localized to the 21 to 47 amino acids of Pre S1 protein. Fusion proteins of full length Pre S1 and GAL4 DNA binding domain did not show transcriptional activation function in mammalian cells. CONCLUSIONS: The transcription activating sequence of HBV Pre S1 protein in yeast overlaps the hepatocyte receptor binding site. The transcriptional activation function of HBV Pre S1 protein in yeast may prevent researchers from using yeast two-hybrid system to clone HBV receptor interacting with Pre S1 protein. However, the Pre S1 protein does not show transcriptional activation function in mammalian cells. Mammalian two-hybrid system may be a practical method to clone the HBV hepatocyte receptor interacting with Pre S1 protein.

[A novel keratin 17 gene mutation in a Chinese pedigree of delayed-onset pachyonychia congenita type II].

OBJECTIVE: To detect the keratin 17 gene mutation in a Chinese pedigree of typical delayed-onset pachyonychia congenita type II (PC-II) and to explore the relationship between the genetic mutation and the phenotype of PC-II. METHODS: The DNA was extracted from the blood samples of 19 patients with PC-II in four generations in the pedigree, 1 unaffected member of the pedigree, and 50 un-related normal persons. Nested PCR was used to amplify the mutation hot spot in the exon 1 of keratin 17 gene. The PCR products were directly sequenced to detect the mutation. RESULTS: Sequencing of the PCR products revealed that the codon 109 (AAC) was mutated as GAC in the nine affected members of the pedigree, causing the substitution of asparagine by aspartic acid in codon 109 (N109D) located in the 1A domain of keratin 17 gene. No such mutation was found in the unaffected member of the pedigree and the 50 unrelated controls. CONCLUSION: The novel missense mutation (N109D) located in the second half of 1A domain of keratin 17 gene underlies the affected members' phenotype, delayed-onset pachyonychia congenita type II.

Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma.

OBJECTIVES: To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma (CSCC). METHODS: Using retrospective analysis, 73 cases of CSCC were selected from Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, which were removed between January 2000 and January 2012. It was considered as experimental group. Meanwhile, 11 cases of normal skin specimens of non tumor patients were selected as control group. The expression level of c-fos and c-myc was compared in the two groups. RESULTS: The expressions of c-fos [72.60% (53/73)] and c-myc [83.56% (61/73)] in experimental group were statistically significant (P≤0.05) compared with control group (0%). Expression of c-myc protein was negatively related to differentiation of CSCC. The difference was statistically significant (χ(2)=7.26, P=0.001<0.05). While expression of c-fos protein was positively related to differentiation of CSCC, which was statistically significant (χ(2)=7.47, P=0.001 2<0.025). CONCLUSIONS: The expression level of c-fos and c-myc can be used as an important indicator of CSCC differentiation, and it has closely connection with the differentiated degree, which can guide clinical prognosis.

Two new susceptibility loci 1q24.2 and 11p11.2 confer risk to severe acne.

Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association. We identify two new susceptibility loci at 11p11.2 (DDB2, rs747650, P(combined)=4.41 × 10⁻9 and rs1060573, P(combined)=1.28 × 10⁻8) and 1q24.2 (SELL, rs7531806, P(combined)=1.20 × 10⁻8) that are involved in androgen metabolism, inflammation processes and scar formation in severe acne. These results point to new genetic susceptibility factors and suggest several new biological pathways related to severe acne.

Isolation and antitumor activities of acidic polysaccharide from Gynostemma pentaphyllum Makino.

Two acidic polysaccharides (GP-B1 and GP-C1) were obtained from Gynostemma pentaphyllum. The molecular weights (Mw) of the two fractions were 79 kDa for GP-B1 and 126 kDa for GP-C1. GP-B1 was composed of Gal, Ara, Man, Rha, Xyl, Glc, GalA and GlcA in a molar ration of 3.5:3.2:0.6:0.9:0.3:0.5:0.6:0.4. GP-C1 consisted of Gal, Ara, Man, Rha, Glc, and GlcA in the proportions of 2.1:1.0:0.3:0.5:0.4:0.9. Among them, GP-B1 treatment had a significant inhibitory effect on the growth of melanoma B16 in vivo and in vitro. Meanwhile GP-B1 could increase the relative spleen weight and stimulate the splenocyte proliferation alone or combined with ConA. Moreover, GP-B1 treatment induced an evident increase in the level of serum TNF-α, IFN-γ, and IL-12 and a reduction for IL-10 production. These results indicate that the antitumor effects of GP-B1 are associated with immunostimulation.