[Distribution of Natural Killer Cell in Patients with Newly Diagnosed Myelodysplastic Syndromes and Its Correlation with Prognosis].

OBJECTIVE: To investigate the distribution of peripheral blood lymphocytes and natural killer (NK) cells, and its influence on the prognosis of patients with myelodysplastic syndromes (MDS). METHODS: The lymphocytes proportion, absolute lymphocyte counts (ALC), NK cell proportion and absolute NK cell counts (ANKC) as well as the related data of 95 MDS patients diagnosed between 2013 and 2017 analyzed retrospectively. The correlation of ALC and ANKC with prognosis was also analyzed. RESULTS: As compared with low ALC patients, MDS patients with ALC≥0.885×109/L had a higher overall response rate (66.7% vs 35.8%) (P＜0.01). The ALC of effective patients after treatment significatitly increased in compaison of ALC at diagnosis. Multivariate analysis indicated that patients with ALC≥0.885×109/L had long overall survival (OS) time in comparison with patients with low level (16.4 vs 12.4 months) (P＜0.05). The OS time of patients with ANKC≥0.110×109/L was shorter in comparison with patients with low level (10.9 vs 16.3 months) (P＜0.01). Otherwise, blast, cytogenetic risks and treatment response were also independent risk factors of MDS (P＜0.05). Revised International Prognostic Scoring System (IPSS-R) combined with ANKC could improve predictive accuracy of IPSS-R alone (AUC 0.718 vs 0.674) (P＜0.05). CONCLUSION: Lymphocytes and NK cells are important for the prognosis evaluation of MDS patients.

Chemerin induced by Treponema pallidum predicted membrane protein Tp0965 mediates the activation of endothelial cell via MAPK signaling pathway.

Chemerin, a chemoattractant protein, is involved in endothelial dysfunction and vascular inflammation in pathological conditions. In a recent study, we observed the upregulation of chemerin in endothelial cells following in vitro treatment with Treponema pallidum. Here, we investigated the role of chemerin in endothelial cells activation induced by the T. pallidum predicted membrane protein Tp0965. Following stimulation of human umbilical vein endothelial cells (HUVECs) with Tp0965, chemerin and its receptor chemerin receptor 23 (ChemR23) were upregulated, companied with elevated expression of Toll-like receptor 2. Furthermore, chemerin from HUVECs activated endothelial cells via chemerin/ChemR23 signaling in an autocrine/paracrine manner, characterized by upregulated expression of intercellular adhesion molecule 1, E-selectin, and matrix metalloproteinase-2. Activation of endothelial cells depended on the mitogen-activated protein kinase signaling pathway. In addition, Tp0965-induced chemerin promoted THP-1-derived macrophages migration to endothelial cells, also via the chemerin/ChemR23 pathway. The RhoA/ROCK signaling pathway was also involved in THP-1-derived macrophages migration in response to chemerin/ChemR23. Our results highlight the role of Tp0965-induced chemerin in endothelial cells dysfunction, which contributes to the immunopathogenesis of vascular inflammation of syphilis.

Ultraviolet-enhanced supercontinuum generation with a mode-locked Yb-doped fiber laser operating in dissipative-soliton-resonance region.

We experimentally demonstrate an all-fiber, ultraviolet-enhanced, supercontinuum generation in a specifically designed seven-core photonic crystal fiber pumped by a picosecond Yb-doped master oscillator power amplifier (MOPA). The MOPA source is seeded by a giant-chirped Yb-doped mode-locked fiber laser operating in the dissipative-soliton-resonance (DSR) region. The DSR is achieved by using a nonlinear optical loop mirror (NOLM) with a fundamental repetition rate of 4.5 MHz and a central wavelength of 1035 nm. An extremely wide optical spectrum spanning from 350 nm to 2400 nm is obtained with a total output power of 6.86 W.

Genome-Wide Identification, Expression, and Functional Analysis of the Alkaline/Neutral Invertase Gene Family in Pepper.

Alkaline/neutral invertase (NINV) proteins irreversibly cleave sucrose into fructose and glucose, and play important roles in carbohydrate metabolism and plant development. To investigate the role of NINVs in the development of pepper fruits, seven NINV genes (CaNINV1-7) were identified. Phylogenetic analysis revealed that the CaNINV family could be divided into α and ß groups. CaNINV1-6 had typical conserved regions and similar protein structures to the NINVs of other plants, while CaNINV7 lacked amino acid sequences at the C-terminus and N-terminus ends. An expression analysis of the CaNINV genes in different tissues demonstrated that CaNINV5 is the dominant NINV in all the examined tissues (root, stem, leaf, bud, flower, and developmental pepper fruits stage). Notably, the expression of CaNINV5 was found to gradually increase at the pre-breaker stages, followed by a decrease at the breaker stages, while it maintained a low level at the post-breaker stages. Furthermore, the invertase activity of CaNINV5 was identified by functional complementation of the invertase-deficient yeast strain SEY2102, and the optimum pH of CaNINV5 was found to be ~7.5. The gene expression and enzymatic activity of CaNINV5 suggest that it might be the main NINV enzyme for hydrolysis of sucrose during pepper fruit development.

Molecular subtyping of Treponema pallidum and associated factors of serofast status in early syphilis patients: Identified novel genotype and cytokine marker.

Serofast, a persistent nontreponemal serological response observed in early syphilis patients after conventional treatment, remains a concern of clinicians and syphilis patients. No consensus has been established, however, that defines an effective treatment strategy and clarifies the pathogenesis. In this study, 517 patients with early syphilis were enrolled and treated. Twelve months after treatment, 79.3% (410/517) of patients achieved serological cure, 20.1% (104/517) were serofast, and 0.6% (3/517) were serological failures. Multivariate analysis demonstrated that older age (>40 years) and lower baseline RPR titer (≤ 1:8) were associated with serofast status. We also identified 21 T. pallidum molecular subtypes among early syphilis patients and detected a new subtype, 14i/a. We found that the proportion of 14i/a type in serofast patients was significantly higher than that in patients with serological cure, predicting an increasing risk of serofast status. Levels of chemerin were higher in the serum of serofast cases than serological cure cases, potentially indicating a novel cytokine marker for serofast in early syphilis patients after therapy. We hope that these results contribute to improve guidelines for the management of syphilis patients who experience serofast.

Efficacy and Safety of Targeted High-Intensity Medium-Band (304-312 nm) Ultraviolet B Light in Pediatric Vitiligo.

BACKGROUND/OBJECTIVES: Phototherapy is a commonly used treatment for vitiligo that has demonstrated safety and efficacy. High-intensity targeted ultraviolet B (UVB) light (304-312 nm) delivered using a phototherapy device is a useful therapeutic option because it can induce repigmentation in a short time without global exposure to radiation, but information regarding this device in children is limited. METHODS: We performed a retrospective analysis of 95 patches of vitiligo in 27 children treated using a targeted phototherapy device. Phototherapy was administered twice a week. RESULTS: After the first 10 treatment sessions, 82 (86.3%) patches demonstrated some repigmentation and 36.8% achieved 50% or more repigmentation. After a mean of 20.4 treatment sessions, 86 patches (90%) demonstrated some repigmentation and 53.7% achieved 50% or more repigmentation. Responses varied depending on the anatomic location of the lesions. Better responses were usually observed on the face and trunk, whereas the extremities typically showed little response. Repigmentation was better in patients with active vitiligo than in those with stable vitiligo, with responses better with a disease duration of 1 year or less than in those with a duration of more than 1 year. There was no statistically significant difference in repigmentation between those with segmental and generalized vitiligo. The only short-term local side effect was mild erythema that required a decrease in dosage in six patients. CONCLUSION: Targeted high-intensity medium-band UVB phototherapy alone can produce clinical improvement in pediatric vitiligo and is well tolerated.

Sesquiterpenes from the fruits of Illicium jiadifengpi and their anti-hepatitis B virus activities.

Two new compounds, 2S-hydroxyl-jiadifenolide (1) and jiadifenlactone acid (2), and eight known compounds were isolated from the fruits of Illicium jiadifengpi. Their structures were analysed using several spectroscopic techniques, including 1D-, 2D-NMR and HR-ESI-MS experiments. The anti-hepatitis B virus (HBV) activities of the isolates were evaluated via HBV transfection of the Hep G2.2.15 cell line. The inhibitory rates of the most active compounds, compounds 4 and 5, on the HBeAg and HBsAg expression were 28.85±3.15% and 17.53±1.81% and 37.93±2.74% and 23.47±9.52% at concentrations of 64.94µM and 61.35µM, respectively.

Tp17 membrane protein of Treponema pallidum activates endothelial cells in vitro.

Tp17, a membrane immunogen of Treponema pallidum subsp. pallidum, was initially recognized as an inflammatory mediator of syphilis. Because the histopathology of syphilis is characterized by endothelial cell abnormalities, we investigated the effects of recombinant Tp17 (rTp17) on endothelial cell activation in vitro. Using real-time reverse transcription-PCR and whole-cell ELISA, we found that rTp17 activated endothelial cells, as demonstrated by the up-regulated expression and increased gene transcription of intercellular adhesion molecule 1 (ICAM-1), E-selectin, and monocyte chemoattractant protein-1 (MCP-1). rTp17 also enhanced the migration and subsequent adhesion of monocytes to endothelial cells as well as increased transendothelial migration of monocytes. These data suggest that the ability of Tp17 to activate endothelial cells may play an important role in the immunopathogenesis of syphilis.

Expression of Cyclooxygenase-2 in Squamous Cell Carcinoma and Keratoacanthoma and its Clinical Significance.

Cyclooxygenase (COX), also known as prostaglandin endoperoxide synthase, catalyzes the conversion of arachidonic acid to prostanoids. There are two different isoforms of COX, referred to as COX-1 and COX-2. Overexpression of COX-2 has been demonstrated in various neoplasms. In this study, we plan to utilize COX-2 in understanding the difference of squamous cell carcinoma and keratoacanthoma which have many similarities in both morphological and histological features. The objective of this study is to study the expression of COX-2 in squamous cell carcinoma and keratoacanthoma and to discuss its clinical significance. The expression of COX-2 in 55 cases of skin tumors (including 30 specimens of squamous cell carcinoma, 25 specimens of keratoacanthoma) and 20 normal skin tissues was detected by immunohistochemical technique. The positive expression of COX-2 was found in 73.3 % (22/30) of squamous cell carcinoma and 12 % (3/25) of keratoacanthoma cases. The positive expression rate of COX-2 in 55 skin tumors (45.5 %) was significantly higher than that in normal skin tissues (5 %) (χ (2) = 10.598 %, P < 0.05). The expression of COX-2 in squamous cell carcinoma (73.3 %) was significantly higher than that in keratoacanthoma (12 %) (χ (2) = 20.69, P < 0.05). COX-2 overexpression may play a potential role in the pathogenesis of skin tumors. The positive expression rate of COX-2 is associated with the malignant degree of the tumor, and also it may help differentiating squamous cell carcinoma from keratoacanthoma.

Low-Dose Topical 5-Aminolevulinic Acid Photodynamic Therapy in the Treatment of Different Severity of Acne Vulgaris.

The objective of this article is to investigate the effectiveness and safety of photodynamic therapy (PDT) with 3.6 % topical aminolevulinic acid (ALA) and a short incubation time with red light in moderate to severe acne. One hundred and thirty-six patients with moderate to severe acne were treated with 3.6 % topical ALA-PDT for three sessions with an interval of 2 weeks. Patients were evaluated for efficacy and safety on week 2, 4, 6, 8, and 12 after the initial treatment. Most patients showed apparent clearance of acne lesions at the treated site after three sessions. The effective treatment rates were increased after the multiple therapies. The clinical outcomes are the best at 4 weeks after the final treatment. The total effectiveness rate and cure rate of the low-dose ALA-PDT procedure is 92.65 and 47.06 %, respectively. Thirty-one patients and nineteen patients showed apparent exacerbation of acne lesions before the 2nd and 3rd treatment, respectively, but all of them showed good or excellent improvement after a three-course treatment. A few patients showed mild relapse including papules and comedos at 8 weeks after the final treatment. No significant differences are found in the effects of different acne severity and different genders. Adverse reactions are mild and transient. A 3.6 % topical ALA-PDT with a short time incubation with red light is a simple and an effective treatment option for moderate to severe acne with mild side effects in Chinese people.

Activated human neutrophil response to perfluorocarbon nanobubbles: oxygen-dependent and -independent cytotoxic responses.

Nanobubbles, a type of nanoparticles with acoustically active properties, are being utilized as diagnostic and therapeutic nanoparticles to better understand, detect, and treat human diseases. The objective of this work was to prepare different nanobubble formulations and investigate their physicochemical characteristics and toxic responses to N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated human neutrophils. The nanobubbles were prepared using perfluoropentane and coconut oil as the respective core and shell, with soybean phosphatidylcholine (SPC) and/or cationic surfactants as the interfacial layers. The cytotoxic effect of the nanobubbles on neutrophils was determined by extracellular O2(.)⁻ release, intracellular reactive oxygen species (ROS), lactate dehydrogenase (LDH), and elastase release. Particle sizes of the nanobubbles with different percentages of perfluorocarbon, oil, and surfactants in ranged 186-432 nm. The nanobubbles were demonstrated to inhibit the generation of superoxide and intracellular ROS. The cytotoxicity of nanobubbles may be mainly associated with membrane damage, as indicated by the high LDH leakage. Systems with Forestall (FE), a cationic surfactant, or higher SPC contents exhibited the greatest LDH release by 3-fold compared to the control. The further addition of an oil component reduced the cytotoxicity induced by the nanobubbles. Exposure to most of the nanobubble formulations upregulated elastase release by activated neutrophils. Contrary to this result, stearylamine (SA)-containing systems slightly but significantly suppressed elastase release. FE and SA in a free form caused stronger responses by neutrophils than when they were incorporated into nanobubbles. In summary, exposure to nanobubbles resulted in a formulation-dependent toxicity toward human neutrophils that was associated with both oxygen-dependent and -independent pathways. Clinicians should therefore exercise caution when using nanobubbles in patients for diagnostic and drug targeting aims.

Identification a novel missense mutation p.R761L in Chinese patients with Darier's disease.

Darier's disease (DD, MIM 124200) is an autosomal dominant inherited disease. It is usually present in teenagers or adults with multiple keratotic papules or plaques in seborrheic areas. Pathogenic mutations in the ATP2A2 gene have been identified. It encodes the sarcoplasmic or endoplasmic reticulum Ca(2+) ATPase isoform 2 (SERCA2). Polymerase chain reaction and direct sequencing of the full coding sequence of ATP2A2 gene were performed to identify the mutation in this family. In this report, we identified a novel mutation of ATP2A2 gene in a Chinese family with DD. It is a novel heterozygous nucleotide G --> T transition at position 2,282 in exon 15 of the ATP2A2 gene. Our study expands the database on the ATP2A2 gene mutations in DD.

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

Multiple familial trichoepithelioma (MFT, OMIM 601606) is an autosomal dominantly inherited disease. It is characterized by numerous skin-colored papules on the central face. Pathogenic mutations in the CYLD gene have been identified. In this report, we identified a novel mutation of CYLD gene in a Chinese family with MFT. It is a novel heterozygous nucleotide G-->A transition at position 2,317 in exon 17 of the CYLD gene. Our study expands the database on the CYLD gene mutations in MFT.

[Mutation analysis of the keratin 9 gene in a pedigree with diffuse epidermolytic plamoplantar keratoderma].

OBJECTIVE: To analyze the mutation of the keratin 9 gene (KRT9) in a pedigree with epidermolytic plamoplantar keratoderma (EPPK). METHODS: Blood samples were obtained from 4 affected and 3 normal individuals in this family. Mutation screening was carried out by polymerase chain reaction (PCR) and direct DNA sequencing. RESULTS: A heterozygous nucleotide C to T transition at position 484 in exon 1 of the KRT9 gene was detected in the 3 affected in this family, but was not found in normal individuals in the family and 100 unrelated individuals. CONCLUSION: A missense mutation (484 C to T) in the KRT9 gene has been detected in this EPPK family, which is probably one of the molecular bases of the pathogenesis of the disease.

A novel 22-bp deletion mutation in a Chinese family with X-linked hypohidrotic ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of the ectodermal dysplasias characterized by an abnormal development of eccrine sweat glands, hair and teeth. Pathogenic mutations in the ED1 gene have been identified. In this family, a 22-bp deletion mutation of exon 8 in the ED1 gene was found in the affected members but not in the healthy individuals and 100 unrelated controls. We add new variant to the knowledge of ED1 mutations in XLHED.

[Analysis on the mutation of ADAR gene in a pedigree with dyschromatosis symmetrical hereditaria].

OBJECTIVE: To analyse the mutation of ADAR gene in a pedigree with dyschromatosis symmetrical hereditaria (DSH). METHODS: A pedigree of DSH was investigated. Mutation scanning was carried out by PCR and direct sequencing. ADAR gene of 50 normal people was also sequenced as control. Through CBMdisc and PubMed, the mutations of ADAR gene were summarized. RESULTS: A novel mutation of c.2447G > A was found in all patients with DSH, but was not found in normal individuals in this DSH family and 50 unrelated controls. There were 64 mutations in ADAR gene. CONCLUSION: A deletion mutation (c.2447G > A) in the ADAR gene has been detected in this DSH family, which is probably one of the molecular bases of the pathogenesis of the disease. Author have summarized a total of 64 mutations in the ADAR gene by previous reports and speculate that the mutation hotspots of ADAR gene might be located in the tRNA-specific and double-stranded RNA adenosine deaminase (ADEAMc) domain.

A novel missense mutation in DSRAD in a family with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the extremities. Pathogenic mutations in the DSRAD gene have been identified. In this report, we identified a Chinese family with a three-generation pedigree of DSH, in which a novel heterozygous nucleotide G-->A transition was found. It is at position 3,125 in exon 12 of the DSRAD gene which induces a R1042H change in the putative deaminase domain of DSRAD. Our study expands the database on the DSRAD gene mutations in DSH.

A new arginine substitution mutation of DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria.

BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. To date, only three articles testified that DSH is caused by the mutations of DSRAD gene (also called ADAR1) encoding for RNA-specific adenosine deaminase. OBJECTIVE: To identify mutations of DSRAD as the disease-causing gene and recognize different mutations giving a clue to insight into the mechanism of DSH. METHODS: We collected a Chinese DSH family consisting of a total of 11 individuals including five DSH patients (three males and two females). The whole coding region of DSRAD was amplified by polymerase chain reaction and products analyzed by direct sequencing. RESULTS: We detected a transition, 3463 C>T, leading to a missense mutation (R1155W) in genomic DNAs of five patients, and the point mutation was not found in normal individuals in this DSH family and in 100 unrelated, population-match control individuals. CONCLUSION: Our data suggests that R1155W missense mutation is a new mutation in exon 15 of DSRAD gene and further testify that DSRAD gene is the pathogenic gene of DSH.

[Study on the compliance and safety of the oral antifungal agents for the treatment of onychomycosis].

OBJECTIVE: To explore the rate of compliance, influencing factors and the safety of patients with onychomycosis under treatment of oral antifungal agents. METHODS: According to the scoring clinical index of onychomycosis (SCIO), 330 patients with onychomycosis, their target nail's integral of the SCIO were calculated and randomly divided into three groups under the baseline of the SCIO integral range. Patients were treated with intermittent pulse itraconazole (A group), continuous terbinafine (B group) and intermittent terbinafine (C group) respectively. Self-administered questionnaire was applied in the survey on every onychomycosis patient. RESULTS: The average rate of compliance was 55.15%. The cure rate for those compliance with doctors' order was 89.01%, while it was only 30.41% for those noncompliant patients The overall non-compliant rate was 44.85%. Among the noncompliant ones, 29.73% were worried about the side effects of medicine, 22.30% thought that they had already been cured, 15.54% was due to economic reasons and 12.16% could not bear the side effects of medicine. It was found that the compliant rates were significantly correlated to ageing, position of the target nails, the integral of the SCIO and the therapy scheme (P < 0.05), while no significant correlations were seen between male and female, culture degree and course (P > 0.1). The frequency of adverse incident of A, B, C groups were 22.73%, 21.43%, 23.15% respectively, but without statistical significance (P > 0.1). Majority of the adverse incidents happened during the first month of therapy but were mild and reversible. CONCLUSION: Our results showed that the overall compliance was low which exerted a significant influence on the curative effect of onychomycosis patients. Factors as ageing, position of the target nail, integral of the SCIO and the therapy scheme had an influence on the compliant rate. When treating onychomycosis with oral itraconazole, the results seemed to be just as safe as when using terbinafine.