A Reliability Assessment Method for Complex Systems Based on Non-Homogeneous Markov Processes.

The Markov method is a common reliability assessment method. It is often used to describe the dynamic characteristics of a system, such as its repairability, fault sequence and multiple degradation states. However, the "curse of dimensionality", which refers to the exponential growth of the system state space with the increase in system complexity, presents a challenge to reliability assessments for complex systems based on the Markov method. In response to this challenge, a novel reliability assessment method for complex systems based on non-homogeneous Markov processes is proposed. This method entails the decomposition of a complex system into multilevel subsystems, each with a relatively small state space, in accordance with the system function. The homogeneous Markov model or the non-homogeneous Markov model is established for each subsystem/system from bottom to top. In order to utilize the outcomes of the lower-level subsystem models as inputs to the upper-level subsystem model, an algorithm is proposed for converting the unavailability curve of a subsystem into its corresponding 2×2 dynamic state transition probability matrix (STPM). The STPM is then employed as an input to the upper-level system's non-homogeneous Markov model. A case study is presented using the reliability assessment of the Reactor Protection System (RPS) based on the proposed method, which is then compared with the models based on the other two contrast methods. This comparison verifies the effectiveness and accuracy of the proposed method.

Highly expressed circ_0000285 from serum and cervical exfoliated cells as a novel biomarker for the diagnosis of early stage-cervical cancer.

Circ_0000285 is reported to play an oncogenic role in the development of cervical cancer (CC). The aim of this research was to investigate the diagnostic power of circ_0000285 in CC. The expression of circ_0000285 in 116 healthy volunteers, 65 early-stage CC (ESCC) patients, and 87 locally advanced CC (LACC) patients was detected by qRT-PCR. The diagnostic values of circ_0000285 for CC and ESCC were evaluated by ROC curves analysis. The circ_0000285 expression was upregulated in serum and cervical exfoliated cells from preoperative CC patients compared to that of healthy volunteers. Increased circ_0000285 expression was found in preoperative LACC patients more than that in ESCC patients. The circ_0000285 expression was downregulated in serum from CC patients after surgery. The postoperative CC patients with high serum circ_0000285 expression was more prone to have a tumour relapse. High circ_0000285 expression was positively correlated with SCC-Ag level and HPV positive rate. The AUC of circ_0000285 for the diagnosis of CC and ESCC were 0.855 and 0.804, better than CA125 and SCC-Ag. When circ_0000285, CA125, SCC-Ag and HPV were combined, the AUC could reach 0.911 and 0.894. In summary, highly expressed circ_0000285 from serum and cervical exfoliated cells might be a promising diagnostic biomarker for ESCC.Impact statementWhat is already known on this subject? The CA125 and SCC-Ag have limitations in the diagnosis of ESCC. Recently, circRNAs have caused great attention and have been developing rapidly in clinical diagnosis of malignant tumours.What do the results of this study add? Highly expressed circ_0000285 from serum and cervical exfoliated cells might be used as a novel, non-invasive biomarker for the diagnosis of ESCC.What are the implications of these findings for clinical practice and/or further research? Circ_0000285 is superior to CA125 and SCC-Ag for the diagnosis of ESCC in clinical practice. The results help to supplement the shortcomings of traditional tumour markers and improve the diagnosis of ESCC.

Cutaneous involvement as initial presentation of multicentric plasmacytic Castleman disease.

Castleman disease (CD) is an unusual lymphoproliferative disorder characterized by multiple lymphadenopathy accompanied by marked systemic inflammatory symptoms. CD can be unicentric (UCD) or multicentric (MCD), and it can be classified into three types based on histopathology: hyaline vascular type, plasma cell type, and mixed hyaline vascular and plasma cell type. CD involving skin is an unusual clinical manifestation. Abnormalities including rash, hyperpigmentation, cherry hemangiomatosis, paraneoplastic pemphigus, and Kaposi sarcoma have been reported to occur in MCD. Here, we reported an unusual case of MCD which presented initially with disseminated dark brown papules, patches, and plaques, and pathologically demonstrated plasma cell type CD, a finding which is rarely reported. The peculiar clinicopathological features will be discussed.

Lymphomatoid papulosis type E with a CD56+ immunophenotype presenting with purpura-like lesions.

Lymphomatoid papulosis (LyP) type E is a recently described variant characterized by the occurrence of large necrotic eschar-like lesions displaying microscopically angioinvasive and angiodestructive infiltrates of CD30+ lymphocytes, frequently coexpressing CD8. Rare cases of LyP type E with a CD56+ immunophenotype have been described. Herein, we describe a 36-year-old woman with LyP type E, characterized by purpura-like lesions on her left ankle. Initially, she presented with left ankle swelling, petechiae and ecchymosis, and rapidly developing necrotic papules, all of which resolved spontaneously over a period of a few months without intentional therapy. Biopsy revealed CD30 and CD56 positive atypical cell infiltrates with marked angiocentricity and angiodestruction. Awareness of this rare LyP variant and its correct recognition, even if the clinical presentation is unusual, is important to avoid aggressive treatment.

ING4 Inhibits Proliferation and Induces Apoptosis in Human Melanoma A375 Cells via the Fas/Caspase-8 Apoptosis Pathway.

BACKGROUND: Inhibitor of growth 4 (ING4) plays a role in regulating the cell cycle, apoptosis, cell invasion and migration, but the mechanisms involved remain to be elucidated. OBJECTIVE: To explore how ING4 affects human malignant melanoma A375 cells. METHODS: Recombinant lentiviral vectors (A375/pLenO-GTP-ING4) were constructed and transfected into A375 cells (experimental group). The impact of ING4 on the proliferation and apoptosis of A375 cells was investigated in in vitro and in vivo experiments in mice using the MTT assay and flow cytometry. RESULTS: In the experimental group, optical density was lower and apoptotic cells were more frequent from days 2-5 (p = 0.000 and p < 0.01); there were smaller xenografts and more apoptotic cells in mice (all p < 0.05); moreover, increased levels of Fas, cleaved caspase-8 and caspase-3, and decreased levels of FasL and procyclic acidic repetitive protein were observed in vitro and in vivo. CONCLUSION: ING4 might suppress proliferation and enhance apoptosis in human malignant melanoma cells by activating Fas-induced apoptosis in a caspase-8-dependent pathway.

Decrease recurrence rate of condylomata acuminata by photodynamic therapy combined with CO2 laser in mainland China: a meta-analysis.

BACKGROUND: Condylomata acuminata (CA) are caused by human papillomavirus. Most conventional therapies for CA have high recurrence rate. OBJECTIVES: To compare the recurrence rate of 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) combined with CO2 laser and CO2 laser alone for CA treatment in mainland China. METHODS: In this meta-analysis, 2,048 cases of CA from 22 articles were divided into two groups. The treatment group was treated by using ALA-PDT combined with CO2 laser, and CO2 laser alone was applied in the control group. The recurrence rate of the two groups was calculated and compared. RESULTS: The recurrence rate was 42.67% (451/1,057) in the control group and 10.29% (102/991) in the treatment group, with a significant statistical difference between the two groups (χ(2) = 271.98, p < 0.0001). CONCLUSION: ALA-PDT combined with CO2 laser was more effective in decreasing the recurrence rate of CA compared with CO2 laser alone. It might offer a wide clinical application for CA treatment.

Imaging of Vulva Syringoma With Reflectance Confocal Microscopy.

Objectives: To investigate the application of reflectance confocal microscopy (RCM) imaging in diagnosis of vulva syringoma. Methods: Patients with lesions suspicious of syringoma on vulva were enrolled in the study. After informed consent was taken, the lesions were photographed and imaged with RCM. The features of the lesion in confocal images were then analyzed and compared with the biopsy findings for histology correlation. Results: Eleven cases in total were included in the study. The typical RCM features observed in syringoma are the presence of round to oval high refractive, and relatively monomorphous mass of varying sizes in the superficial and middle dermis, usually surrounded with 1-2 layers of light-dark line structures, which were further confirmed by histological evaluation. Ten cases showed classic features of syringoma and 1 case exhibited milia in RCM images. Conclusions: Syringoma has distinct features in RCM imaging, which correlates well with histological findings, highlighting the potential role of RCM in the diagnosis and differential diagnosis of vulva syringoma.

The impact of IL-10 and CYP3A5 gene polymorphisms on dose-adjusted trough blood tacrolimus concentrations in early post-renal transplant recipients.

BACKGROUND: The strong inter-individual pharmacokinetic variability and the narrow therapeutic window of tacrolimus (TAC) have hampered the clinical application. Gene polymorphisms play an important role in TAC pharmacokinetics. Here, we investigate the influence of genotypes of IL-10, CYP3A5, CYP2C8, and ABCB1 on dose-adjusted trough blood concentrations (the C0/D ratio) of TAC to reveal unclear genetic factors that may affect TAC dose requirements for renal transplant recipients. METHODS: Genetic polymorphisms of IL-10, CYP3A5, CYP2C8, and ABCB1 in 188 renal transplant recipients were determined using Kompetitive Allele Specific PCR (KASP). Statistical analysis was applied to examine the effect of genetic variation on the TAC C0/D at 5, 10, 15, and 30 days after transplantation. RESULTS: Recipients carrying the IL-10 -819C > T TT genotype showed a significantly higher TAC C0/D than those with the TC/CC genotype (p < 0.05). Additionally, the TAC C0/D values of recipients with the capacity for low IL-10 activity (-819 TT) engrafted with CYP3A5 non-expressers were higher compared to the intermediate/high activity of IL-10 -819C > T TC or CC carrying CYP3A5 expressers, and the difference was statistically significant at different time points (p < 0.05). CONCLUSIONS: Genetic polymorphisms of IL-10 -819C > T and CYP3A5 6986A > G influence the TAC C0/D, which may contribute to variation in TAC dose requirements during the early post-transplantation period. Detecting IL-10 -819C > T and CYP3A5 6986A > G polymorphisms may allow determination of individualized tacrolimus dosage regimens for renal transplant recipients during the early post-transplantation period.

Pluronic® F127 stabilized reduced graphene oxide hydrogel for the treatment of psoriasis: In vitro and in vivo studies.

Psoriasis is a chronic inflammatory disease that can be effectively treated using topical cyclosporine. However, topical delivery is extremely challenging owing to the physicochemical nature of cyclosporine, as well as the thick psoriatic stratum corneum. In the present study, for the first time, we attempted to formulate a cyclosporine-loaded Pluronic® F127 stabilized reduced graphene oxide hydrogel to improve cyclosporine permeation and retention in the affected tissue for effective psoriasis treatment. The attachment of Pluronic® F127 on reduced graphene oxide was confirmed using Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray diffraction. The scanning electron microscopy image demonstrated a wrinkled and flattened nanosheet surface with Pluronic® F127 micelles. Ex vivo permeation data demonstrated an increase in cyclosporine permeation with increasing levels of reduced graphene oxide in the hydrogel. The hydrogel showed sufficient mechanical properties (texture analyzer report) for topical application, without any sign of irritation on rabbit skin. In the drug retention study, the C-P-rGO-500 hydrogel demonstrated maximum drug trapping inside the skin tissue. In the efficacy study in mice, the C-P-rGO-500 hydrogel decreased hyperplasia and tissue damage in psoriatic skin. Thus, the ability of the reduced graphene oxide nanocarrier to improve cyclosporine permeation, as well as retention in skin tissue, could be successfully utilized for effective psoriasis treatment, minimizing side effects encountered with oral and systemic routes.

Downregulated Long Noncoding RNA DGCR5 Acts as a New Promising Biomarker for the Diagnosis and Prognosis of Ovarian Cancer.

Emerging evidence have indicated that dysregulated long noncoding ribonucleic acids act as a novel diagnostic and therapeutic target in the progression of ovarian cancer. Long noncoding RNA DiGeorge syndrome critical region gene 5 has been reported to participate in some types of human cancer progresses, but its clinical roles in ovarian cancer had been rarely reported. This study aimed to explore the expression, clinicopathological features, diagnostic, and prognostic values of DiGeorge syndrome critical region gene 5 in ovarian cancer. The total levels of DiGeorge syndrome critical region gene 5 transcript variant 1 (NR_002733.2) and 2 (NR_045121.1) in patients with ovarian cancer were determined by quantitative reverse transcription polymerase chain reaction. The correlation of DiGeorge syndrome critical region gene 5 expression with clinicopathological factors was statistically analyzed by χ2 test. Overall survival analysis was carried out with the Kaplan-Meier curves with the log-rank test. Univariate and multivariate Cox regression analyses were performed to identify the prognostic significance of DiGeorge syndrome critical region gene 5 expression. Receiver operating characteristic curves were constructed to estimate the diagnostic and prognostic usefulness of DiGeorge syndrome critical region gene 5 in ovarian cancer. Results showed that relative DiGeorge syndrome critical region gene 5 expression was reduced by 36.81% and 65.79% in ovarian cancer tissues of patients and Gene Expression Omnibus DataSets (GSE119056) in contrast to normal tissues, respectively. Patients with lymph node metastasis and distant metastasis exhibited lower levels of DiGeorge syndrome critical region gene 5 in contrast to those patients with non-lymph node metastasis and non-distant metastasis, respectively. Low expression of DiGeorge syndrome critical region gene 5 was significantly associated with large tumor size, more lymph node metastasis, present distant metastasis, advanced clinical stage, and short overall survival in patients with ovarian cancer. Low expression of DiGeorge syndrome critical region gene 5 was an independent unfavorable prognostic factor for overall survival in patients with ovarian cancer. Receiver operating characteristics curves for prognosis yielded significant area under curves for lymph node metastasis, clinical stage, and overall survival. In conclusion, our study demonstrated that downregulated DiGeorge syndrome critical region gene 5 may be a new promising biomarker for predicting clinical progression and prognosis in patients with ovarian cancer.

Immobilization of Rhizomucor miehei lipase onto the organic functionalized SBA-15: Their enzymatic properties and glycerolysis efficiencies for diacylglycerols production.

In this study, mesoporous silica SBA-15 was modified by organic functional groups through silanization. Series of organosilane compounds were grafted onto the SBA-15, and the obtained functionalized carriers were then used to immobilize the lipase from Rhizomucor miehei (RML). The enzymatic properties of the obtained immobilized RML samples were evaluated, and the catalytic efficiencies in glycerolysis of triacylglycerols (TAG) reaction were studied. Compared with the parent SBA-15 immobilized RML, the organic modification gave a maximum improvement of enzymatic activity from 200.00 to 13211.11 U/g; in addition, TAG conversion and diacylglycerols (DAG) content increased from 21.28 to 84.24% and 15.45 to 59.03% respectively. The organic modification also decreased the sensitivity of immobilized RML in extreme pH values and increased their thermostability.

Immobilization of Candida antarctica Lipase B onto organically-modified SBA-15 for efficient production of soybean-based mono and diacylglycerols.

In this study, SBA-15 was modified by a series of silane coupling reagents and later used to immobilize Candida antartica lipase B (CALB). The enzymatic properties of the immobilized CALB samples were studied. In addition, the catalytic performance in glycerolysis of soybean oil for diacylglycerols (DAG) production was also investigated. The highest enzymatic activity up to 6100.00 ±â€¯246.41 U/g was observed from the propyl methacrylate group modified SBA-15 supported CALB. No loss of activity was observed from the propyl methacrylate group modified SBA-15 supported CALB, but a higher-than-initial activity was notably found from 3-aminopropyl group and n-octyl group modified SBA-15 supported CALB after a 4-h incubation in air at 70 °C. 1-isocyanatopropane group modified SBA-15 supported CALB exhibited selectivity for DAG production. DAG content up to 61.90 ±â€¯2.38 wt% and a DAG/MAG ratio at 3.11 ±â€¯0.08 was obtained after a 24-h reaction at 60 °C in a solvent-free system.

Enhanced anti-melanoma efficacy of interferon α-2b via overexpression of ING4 by enhanced Fas/FasL-mediated apoptosis.

Melanoma, is a highly aggressive and the most lethal form of skin cancer, and is known to be resistant to current therapeutic modalities. Interferon (IFN)-α2b is an immunostimulatory cytokine and is used to treat melanoma by inhibiting proliferation and promoting apoptosis of cells. However, there is a need to improve the efficacy of IFN-α2b. Inhibitor of growth family member 4 (ING4) has been reported to function as a tumor suppressor and is involved in regulating cell cycle progression, apoptosis, cell migration and invasion. Previously studies have also reported that caspase-3, caspase-8, poly (ADP-ribose) polymerase (PARP) and Fas/Fas ligand (FasL) pathways are involved in the process of apoptosis. In the present study, it was investigated whether overexpression of ING4 is able to enhance IFN-α2b response in human melanoma cells. It was determined that the overexpression of ING4 was able to increase the effects of IFN-α2b, and induce cell death and apoptosis in melanoma cells. Furthermore, the overexpression of ING4 resulted in decreased expression of PARP, caspase-3 and -8. The expression of cleaved PARP, cleaved caspase-3, cleaved caspase-8, Fas and FasL was increased in the A375 melanoma cell line. These results demonstrate that the overexpression of ING4 is able to enhance the anti-melanoma activity of IFN-α2b. These findings provide a potential therapeutic strategy where a combination of ING4 overexpression and IFN-α2b treatment may lead to higher levels of apoptosis in melanoma cells.

microRNA-130a Promotes Human Keratinocyte Viability and Migration and Inhibits Apoptosis Through Direct Regulation of STK40-Mediated NF-κB Pathway and Indirect Regulation of SOX9-Meditated JNK/MAPK Pathway: A Potential Role in Psoriasis.

Psoriasis is a chronic inflammatory skin disorder. The aim of this study was to determine a potential role of microRNA (miR)-130a in psoriasis, and underlying mechanism. Expression levels of miR-130a in psoriasis specimens and normal skin tissues were analyzed. MiR-130a mimic, inhibitor, miR-control, small interfering RNA (siRNA) specific serine/threonine kinase 40 (STK40), or sex-determining region Y chromosome-box 9 (SOX9) were transfected to human keratinocyte HaCaT cells, respectively. After transfection, the cell viability, apoptosis, and migration were determined. Luciferase reporter assay, quantitative reverse transcription-polymerase chain reaction, and western blot were performed to explore whether STK40 was a target of miR-130a. The effects of aberrant expressions of miR-130a, STK40, or SOX9 on key proteins of NF-κB and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) pathway were assessed. The miR-130a levels were significantly higher in patients with psoriasis compared to the healthy controls (p < 0.01). Overexpressing miR-130a strikingly promoted HaCaT cell viability and migration and inhibited apoptosis (p < 0.01 or p < 0.05). We confirmed that STK40 was a direct target of miR-130a, and STK40 was involved in miR-130a-induced cell functions. Overexpressing miR-130a significantly upregulated NF-κB p65, SOX9, p-c-Jun, p-JNK, and p-p38MAPK proteins and silencing miR-130a downregulated them. In addition, silencing STK40 alleviated the effects of anti-miR-130a on SOX9 expression. Furthermore, silencing SOX9 also decreased levels of p-c-Jun, p-JNK, and p-p38MAPK proteins. MiR-130a regulates human keratinocyte HaCaT viability, migration and apoptosis might be by direct regulation of STK40-mediated NF-κB pathway and by indirect regulation of SOX9-mediated downstream JNK/MAPK signaling pathway.