Surface air plasma-induced cell death and cytokine release of human keratinocytes in the context of psoriasis.

BACKGROUND: Cold atmospheric plasma (CAP) has shown promise for wound healing, although little is understood of the underpinning mechanisms. Little has been reported so far of its potential use in the treatment of immune-mediated diseases such as psoriasis. OBJECTIVES: To study CAP-induced cell death and cytokine release in human keratinocytes as a first assessment of possible CAP use for psoriasis. METHODS: Using a CAP generator free of energetic ions, we observed its effects on keratinocytes in terms of morphology, cell viability and apoptosis, intracellular and mitochondrial reactive oxygen species (ROS), lysosomal integrity and mitochondrial membrane potential; and on secretion and expression of eight cytokines at protein and gene levels. RESULTS: CAP-induced reduced cell viability, apoptotic death and production of intracellular and mitochondrial ROS in dose-dependent manner. Mitochondrial dysfunction and lysosomal leakage were found in CAP-treated cells. It also induced release of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF), and enhanced the mRNA expression of IL-1ß, IL-6, IL-8, IL-10, TNF-α, interferon-γ and VEGF. By contrast, IL-12 declined monotonically. CONCLUSIONS: The results suggest that with appropriate control of its dose, physical plasma could induce cell death via apoptotic pathways and enable simultaneous reduction in IL-12. These effects may be used to suppress keratinocyte hyperproliferation and to target T-cell activation to control amplification of inflammation. This provides an initial basis for further studies of CAP as a potential therapeutic option for inflammatory and immune-related diseases in dermatology, including psoriasis.

Cross-sectional and dynamic change of serum metabolite profiling for Hepatitis B-related acute-on-chronic liver failure by UPLC/MS.

Summary Acute-on-chronic liver failure(ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function and results in the failure of one or more organs with high short-term mortality. The focus of this study was to discover noninvasive and reliable biomarkers for the diagnosis and prognosis of hepatitis B-related ACLF. Ultra-performance liquid chromatography-mass spectrometry (UPLC/MS) was used to analyse serum metabolites of 28 patients with hepatitis B-related ACLF, 35 patients with Child-Pugh A cirrhosis, 30 patients with chronic hepatitis B and 35 healthy volunteers (HS). Characteristic metabolites were screened, identified and dynamically tracked to investigate their value for diagnosis and prognosis. After comparing serum metabolic profile of hepatitis B-related ACLF and Child-Pugh A cirrhosis, 99 characteristic metabolites were selected, and 38 of them were identified. Dynamic tracking model demonstrated that 17 metabolites were related to prognosis of hepatitis B-related ACLF, and there were also 11 metabolites which improved with treatment in the survival group. The correlations between these characteristic metabolites and the model for end-stage liver disease score were strong. These observations contributed to the investigation of the mechanisms of hepatitis B-related ACLF manifestation and progression on the metabolic level, and they provided information for the identification of biomarkers for the diagnosis and prognosis of hepatitis B-related ACLF.

Investigation of the association between psoriasis and human leucocyte antigens A by means of meta-analysis.

BACKGROUND: The association between psoriasis and human leucocyte antigen A (HLA-A) does not reach a consensus. OBJECTIVES: To clarify the association between psoriasis and HLA-A. METHODS: Predefined selection criteria were applied to all relevant case-control studies (from 1972 to 2013) in two English databases. RESULTS: Twenty-three eligible articles covering 12 227 participants were included, in which 28 alleles were reported associated with psoriasis. Our meta-analysis results showed that nine alleles were susceptible, 12 were protective and seven were unassociated. Subgroup analyses were conducted in terms of race, clinical type and onset age. For unspecific psoriasis, only one strongly susceptible allele was found in Caucasian and three were in Asian; three strongly protective alleles were reported in Caucasian and only one was found in Asian. There was no common allele to both races. For psoriasis vulgaris, there was no strongly susceptible allele in Caucasian but two in Asian; two strongly protective alleles were found in Caucasian and another two were in Asian. For psoriatic arthritis, two strongly susceptible alleles and one strongly protective allele were reported in Caucasian cases. For psoriasis guttate, only one strongly protective allele was found in Caucasian. In terms of onset age, A*01, A*02, A*03, A*26 and A*30 alleles were more susceptible to type I psoriasis than to type II, and it showed a stronger association in those with family history. CONCLUSIONS: Psoriasis is associated with a number of HLA-A alleles, some are susceptible, some are protective. The association of some alleles is different in terms of different races, clinical types and onset age.

Meta-analysis of the association between psoriasis and human leucocyte antigen-B.

BACKGROUND: Currently there is no consensus about the association between psoriasis and human leucocyte antigen (HLA)-B. OBJECTIVES: To clarify the association between psoriasis and HLA-B. METHODS: Articles were selected, following predefined criteria, from case-control studies on the association between psoriasis and HLA-B published between 1 January 1972 and 11 November 2012, and included in the PubMed and ISI Web of Knowledge databases. RESULTS: Thirty-seven eligible articles covering 16 206 participants (14 644 white and 1562 Asian) were included. Sixty HLA-B alleles were reported, among which 26 were associated with susceptibility to disease, 24 were protective and 10 were unassociated. For unspecific psoriasis, there were three strongly susceptible alleles (OR ≥ 3·0) in white and four in Asian subjects, with HLA-B*57 and HLA-B*13 common to both races; there were four strongly protective (OR ≤ 0·3) alleles in white and seven in Asian subjects, with HLA-B*07 common to both. For psoriasis vulgaris, nine alleles were strongly associated with susceptibility in white subjects and five in Asians, with HLA-Bw*37 and HLA-B*57 in both; three alleles were strongly protective in white subjects and one in Asians, with none in common. Cases of psoriatic arthritis and guttate psoriasis were reported only in white subjects, with eight and seven strongly susceptible alleles, and two and three strongly protective alleles, respectively. Analyses of onset age showed that praecox patients with family history were significantly more susceptible to HLA-B*13 and HLA-B*57 than tardive ones. CONCLUSIONS: A significant association was identified between psoriasis and 50 HLA-B alleles. The association varied in terms of race, and clinical type and onset age of psoriasis.

A novel mutation of CYLD in a Chinese family with multiple familial trichoepithelioma.

BACKGROUND: Trichoepithelioma is a benign cutaneous tumour that originates from hair follicles and occurs either as a sporadic non-familial or a multiple-familial type. Recently, several mutations in the cylindromatosis (CYLD) gene have been reported in multiple familial trichoepithelioma (MFT). OBJECTIVES: To report a Chinese family of MFT and to explore the genetic mutation. METHODS: A Chinese pedigree of typical MFT was subjected to mutation detection in CYLD. Direct sequencing of all PCR products of the whole coding regions of CYLD gene was performed to identify the mutation. RESULTS: The c.1178-1179delCA (p.T393fs) mutation was found in CYLD gene in the affected members, but not in the healthy individuals in the family. CONCLUSION: Our study found a novel mutation in exon 10 of CYLD gene.

Sella turcica anatomy by three-dimensional computed tomography for an endonasal transsphenoidal approach to pituitary adenoma.

BACKGROUND: The aim of this study was to identify the anatomic landmarks of sella turcica on the surface of the head, and to investigate the feasibility of studying sella turcica anatomy individually by three-dimensional computed tomography (3D-CT) before an endonasal transsphenoidal operation. PATIENTS AND METHODS: The three-dimensional anatomic structures of the heads of 49 patients were studied by 3D-CT using image reconstruction with surgical clip image registration. The tip of the nose and the apex of the ear helix were used as surface markers on the head, and the locations of the sphenoid sinus and sellar floor with respect to a line defined by these 2 markers were investigated. Using an endonasal transsphenoidal approach with a surgical trajectory guided by the nose tip-ear apex line and 3D-CT anatomic images of the sella turcica, 12 patients with pituitary adenoma were treated surgically. RESULTS: The nose tip-ear apex line passed through the sphenoid sinus in 100% of the cases and through the sellar floor in 41.4% of the cases. The mean distance from the sellar floor clivus point perpendicularly to the nose tip-ear apex line was 3.5±2.0 mm. The 3D-CT imaging clearly showed the configuration of the sphenoid sinus, bone septum, optic protuberance, carotid protuberance and the sellar floor. 12 pituitary adenomas were resected totally. CONCLUSION: The nose tip-ear apex line provides a precise, simple, and practical tool for orienting the sphenoid sinus, sellar floor and surgical trajectory of the endonasal transsphenoidal approach. 3D-CT images more clearly and intuitively display the sella turcica anatomy. Preoperative 3D-CT increases the surgeon's confidence in endonasal transsphenoidal operations and should be routinely performed in patients with pituitary adenomas.

Serum peptide profiles during progression of chronic hepatitis B virus infection to liver failure.

Chronic hepatitis B virus (HBV)-infected patients with liver failure have a poor prognosis, and no satisfactory biomarkers are available for diagnosis before the end-stage. We explored serum peptide profiling for diagnosis and prediction of progression to liver failure in HBV-infected patients. Serum samples (164) from healthy subjects (n = 20), or subjects with chronic hepatitis B without cirrhosis and liver failure [chronic hepatitis B subjects without cirrhosis and liver failure (CHB); n = 33], with compensated liver cirrhosis (compensated liver cirrhosis (LC); n = 35), with acute-on-chronic liver failure [acute-on-chronic liver failure (ACLF); n = 38] or with chronic liver failure [chronic liver failure (CLF), n = 38] were applied to ClinProt magnetic beads, and bound peptides/proteins were analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Our classification diagnostic models of liver disease were generated based on the Genetic Algorithm (GA) and Quick Classifier Algorithm (QC). Differentially expressed peptides were found among all test groups, with patterns of difference that readily distinguished between healthy and various HBV-associated liver disease samples. The model generated seven characteristic peptide peaks at 4053 m/z, 3506 m/z, 4963 m/z, 9289 m/z, 2628 m/z, 3193 m/z and 6432 m/z, giving overall predictive capability of 54.27%. Two-way comparisons of LC, ACLF or CLF vs CHB had predictive capabilities of 79.8%, 91.41% and 97.99%, respectively. Comparisons of ACLF or CLF vs LC were predictive at 87.72% and 82.18%, respectively and ACLF vs CLF was predictive at 75.05%. These classification diagnostic models generated by different peptide peaks were further validated in blinded tests with 67-100% accuracy. Serum peptide patterns vary during progression of chronic HBV infection to liver failure and may be used to distinguish different stages of the disease.

Quality of life in patients with lepromatous leprosy in China.

BACKGROUND: Leprosy has an impact on patients' quality of life (QoL). However, there has been no study specifically on the impact of the severest type of leprosy-lepromatous leprosy on QoL. OBJECTIVE: To describe the use of Dermatology Life Quality Index (DLQI) among patients with lepromatous leprosy in China. METHODS: Sixty-four inpatients with lepromatous leprosy of Shangluo hospital and Hanzhong hospital and sixty-four controls (healthy volunteers or patients with other dermatoses) matched for age and gender were asked to complete DLQI questionnaires from 2 September 2008 to 20 December 2008. Extensive data were collected besides DLQI, including demographic data and disease-related characteristics. Absence or presence of disability among patients with lepromatous leprosy was evaluated at the same time. RESULTS: The overall mean DLQI score for lepromatous leprosy (18.78) was higher than that for control (9.00) (P < 0.001). Patients with lepromatous leprosy scored significantly higher for all items (P < 0.001) except Q4 (clothes choice). Controls scored significantly lower for all domains of DLQI. Scores of LL increased markedly with increasing clinical severity, but were not associated with educational level, gender, age and disease duration. The inter-item correlation averaged 0.240 and Cronbach's alpha was 0.759, indicating high internal consistency. CONCLUSIONS: This is the first exclusive study to attempt to measure the impact of lepromatous leprosy on QoL. Lepromatous leprosy has a severe impact on QoL.

[A study on quality standard of Rabdosia lophanthoides (Buch.-Ham. ex D. Don Hara)].

OBJECTIVE: To establish quality standards for safe and correct use of Rabdosia lophanthoides. METHOD: Field investigation and pharmacognostic study. RESULT: R. lophanthoides was confirmed as a derivative of R. lophanthoides. CONCLUSION: A convenient and effective method for identifying the herb has been established.

A novel frameshift mutation in the cylindromatosis (CYLD) gene in a Chinese family with multiple familial trichoepithelioma.

Multiple familial trichoepithelioma (MFT) (OMIM: 601606) is an autosomal dominantly inherited disorder characterized by numerous, skin-colored papules and nodules with pilar differentiation. Recently, several mutations in the cylindromatosis (CYLD) gene have been reported in MFT. In this study, a mutation analysis of the CYLD was conducted in a Chinese pedigree of typical MFT. Affected individuals were identified through probands from Shanxi Province, China. Lesional skin biopsy of the proband revealed the typical histopathological characteristics of trichoepithelioma. Individuals belonging to five consecutive generations were similarly affected, which indicated an autosomal dominant inheritance pattern. Genomic DNA was extracted from peripheral blood lymphocytes using standard phenol/chloroform extraction method. All the coding exons (4-20) and exon-intron boundaries of the CYLD gene were amplified by polymerase chain reaction (PCR). Direct sequencing of all PCR products amplified from the complete coding regions of the CYLD gene was performed to identify mutations. Sequencing of the CYLD gene was performed in a further 100 unrelated, unaffected control individuals to exclude the possibility of polymorphism. A novel heterozygous frameshift mutation c.1169_1170delCA (p.Thr390Argfs) was identified in exon 10 of the CYLD gene in the affected family members. This mutation was also detected in unaffected family members, but not in the unrelated, healthy individuals who were also analyzed. Our study expands the database on the CYLD gene mutations in MFT and should be useful in providing genetic counseling and prenatal diagnosis for families affected by MFT.

Purification and characterization of a DNA polymerase-template complex in mouse ascites tumor cells.

A DNA polymerase-template complex found in mouse Erhlich ascites tumor cells was purified by twice discontinuous gradient centrifugations and agarose gel filtration. After purification, the specific activity of the complex increased about 500-fold. The size of the complex was found to be 510,000 daltons. The shape of the complex was globular under electron microscope. Its diameter was between 100-110 A. The complex was isolated into two main enzyme proteins and a homogeneous DNA template by DEAE cellulose chromatography. The main enzyme had a molecular weight of 300,000 daltons and a sedimentation coefficient of 9.5s. The endogenous template DNA showed a single zone in polyacrylamide gel electrophoresis analysis. The sedimentation coefficient was determined to be 3.8s.

Keratin 17 mutation in pachyonychia congenita type 2 with early onset sebaceous cysts.

BACKGROUND: Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias caused by mutations in four differentiation-specific keratin genes. Two major clinical subtypes of PC have been generally recognized. Symmetrically thickened fingernails and toenails are the defining characteristic of PC type 2 (PC-2) with onset at infancy. Pilosebaceous cysts are the best hallmark of PC-2, but they usually occur at puberty. OBJECTIVES: To report a Chinese pedigree of PC-2 with unusually early onset sebaceous cysts and to explore the genetic mutation and its phenotype. METHODS: Exon 1 of keratin 17 was amplified by polymerase chain reaction (PCR) from genomic DNA from the three patients in the pedigree, the proband, his half-sister and his younger son, two unaffected members in the pedigree and 50 unrelated and unaffected people. PCR products were directly sequenced to detect the mutation. RESULTS: Direct sequencing of the PCR products revealed a heterozygous 275A-->G mutation in all three affected members. This mutation predicts the substitution of asparagine by serine in codon 92 (N92S) located in the 1A domain of keratin 17. CONCLUSIONS: Mutation in the 1A domain of keratin 17 underlies the affected members' phenotype, PC-2 with early onset sebaceous cysts and late-onset thickened fingernails and toenails. The onset of the cysts is very early in some people within this family and the age at onset of thickened fingernails and toenails is variable within the family, implying the existence of modifying factors.

A new mutation in the linker 12 domain of keratin 5 in a Chinese family with Weber-Cockayne epidermolysis bullosa simplex.

A previously undescribed missense mutation was detected in the L12 domain of keratin 5 (K5) in a Chinese family with Weber-Cockayne epidermolysis bullosa simplex. Direct sequencing of the PCR products identified a single base substitution (983A-->G) that changes the aspartic acid residue at codon 328 to glycine in all affected family members, while no mutation was observed either in the healthy individual or 50 unrelated control samples. Asp328 of K5 is remarkably conserved among all type II keratins. D328G is the fourth mutation found to affect this residue in K5-related epidermolysis bullosa simplex, indicating the importance of Asp328 for K5 structure and the dramatic effect that fine changes can have on keratin intermediate filament integrity.