Identification and Validation of Novel Metastasis-Related Immune Gene Signature in Breast Cancer.

Background: Distant metastasis remains the leading cause of death among patients with breast cancer (BRCA). The process of cancer metastasis involves multiple mechanisms, including compromised immune system. However, not all genes involved in immune function have been comprehensively identified. Methods: Firstly 1623 BRCA samples, including transcriptome sequencing and clinical information, were acquired from Gene Expression Omnibus (GSE102818, GSE45255, GSE86166) and The Cancer Genome Atlas-BRCA (TCGA-BRCA) dataset. Subsequently, weighted gene co-expression network analysis (WGCNA) was performed using the GSE102818 dataset to identify the most relevant module to the metastasis of BRCA. Besides, ConsensusClusterPlus was applied to divide TCGA-BRCA patients into two subgroups (G1 and G2). In the meantime, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a metastasis-related immune genes (MRIGs)_score to predict the metastasis and progression of cancer. Importantly, the expression of vital genes was validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). Results: The expression pattern of 76 MRIGs screened by WGCNA divided TCGA-BRCA patients into two subgroups (G1 and G2), and the prognosis of G1 group was worse. Also, G1 exhibited a higher mRNA expression level based on stemness index score and Tumor Immune Dysfunction and Exclusion score. In addition, higher MRIGs_score represented the higher probability of progression in BRCA patients. It was worth mentioning that the patients in the G1 group had a high MRIGs_score than those in the G2 group. Importantly, the results of RT-qPCR and IHC demonstrated that fasciculation and elongation protein zeta 1 (FEZ1) and insulin-like growth factor 2 receptor (IGF2R) were risk factors, while interleukin (IL)-1 receptor antagonist (IL1RN) was a protective factor. Conclusion: Our study revealed a prognostic model composed of eight immune related genes that could predict the metastasis and progression of BRCA. Higher score represented higher metastasis probability. Besides, the consistency of key genes in BRCA tissue and bioinformatics analysis results from mRNA and protein levels was verified.

Chest Pain With Exercise-Induced Left Bundle-Branch Block-Is There a Connection?

This case report describes a patient in their early 60s with chest pain during exertion.

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Solanum rostratum is a severely invasive alien plant species in China. Using four S. rostratum populations and non-invasive congener S. americanum, we conducted a common garden experiment to compare their breeding systems. No significant difference in average seed set between the two species under open pollination and supplementary pollination conditions. However, under the bagged self-pollination condition, S. rostratum had significantly lower average seed set (29.5%) than S. americanum (47.0%). No fertile seeds were detected in the emasculation treatments for both species, suggesting no autonomous apomixis in them. S. rostratum had a lower average autofertility index (0.38) than S. americanum (0.64). S. rostratum had higher average pollen limitation index (0.29) and average pollinator's contribution index (0.49) than S. americanum (0.08 and 0.31, respectively). S. rostratum was found in 12 provinces of China and in 3835 locations globally, which were lower than S. americanum with 18 Chinese provinces and 10897 locations globally. The invasive alien S. rostratum had lower self-compatibility than the non-invasive alien S. americanum. Thus, the invasiveness of those two species was not significantly correlated with their self-compatibility, but positively correlated with their distribution range.

CXC Chemokine Receptor Type 4 Antagonism Ameliorated Allograft Fibrosis in Rat Kidney Transplant Model.

OBJECTIVES: In this study, we evaluated the effects of CXC chemokine receptor type 4 and stromal cell-derived factor 1 signaling in the progression of chronic allograft nephropathy in a rat model. MATERIALS AND METHODS: Experimental rats were divided into 3 groups: Lewis-to-Lewis isograft transplant (group A), Fisher 344 rat-to-Lewis allograft transplant with immunosuppressant cyclosporine (group B), and Fisher 344 rat-to-Lewis allograft transplant treated with cyclosporine and the CXC chemokine receptor type 4 antagonist AMD3100 (1 mg/kg/d) (group C). On day 90 after the operation, renal graft function, proteinuria, and histologic Banff score were measured. The expression levels of transforming growth factor ß1 and collagen IV were determined by quantitative real-time polymerase chain reaction. RESULTS: Renal function and urinary protein were increased in allografts of groups B and C compared with isografts of group A. The Banff score was significantly decreased in the AMD3100-treated animals (group C), with renal fibrosis being reduced. In addition, overexpressed levels of transforming growth factor ß1 and collagen IV in group B allografts were significantly reduced versus that shown with treatment with the CXC chemokine receptor type 4 antagonist in group C. CONCLUSIONS: Together, these data strongly implicate that CXC chemokine receptor type 4 antagonism alleviated renal interstitial fibrosis in long-term surviving allografts by down-regulating expression of transforming growth factor ß1.

Complete mitochondrial genome of Gnathopogon taeniellus (Cypriniformes: Cyprinidae).

The complete mitochondrial genome of Gnathopogon taeniellus was first determined in this study. It is 16,596 bp in length, contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and one control region in the typical vertebrate gene order and transcriptional direction. There are total of 29 bp short overlaps and 34 bp non-coding intergenic spacers were found in the mitogenome. Overall nucleotide base composition of light strand is 29.3% A, 25.8% C, 17.9% G and 27.0% T. Two start codons (ATG and GTG) and two stop codons (TAG and TAA/T) were used in the protein-coding genes. The origin of light strand replication (OL) was identified between tRNA(Asn) and tRNA(Cys) genes and could fold a hairpin structure. The nucleotide composition of control region is 31.8% A, 20.9% C, 14.0% G and 33.3% T.

Arthritis as an important determinant for psoriatic patients to develop severe vascular events in Taiwan: a nation-wide study.

BACKGROUND: Psoriasis is an important systemic inflammatory disease that often leads to severe vascular diseases. This study was launched to determine if joint involvement affects incidence of vascular comorbidities in psoriatic patients. In addition, potential vasculo-protective effects of methotrexate in psoriatic patients were also evaluated. METHOD: A population-based retrospective cohort study was conducted using the Taiwanese National Health Insurance database spanning from 1996 to 2006. Accordingly, 7648 and 284 psoriatic patients without or with arthritis, respectively, were identified. To ensure the temporal relationship between different events, those with date of first diagnosis psoriasis during the year of 1996 were excluded from subsequent analyses. In addition, those with diagnosis of cerebrovascular or cardiovascular diseases prior to onset of psoriasis were also excluded from relevant subsequent analyses. RESULT: Taking psoriatic patients without arthritis as the referent group, the hazard ratio for incident cerebrovascular disease was 1.82 (95% CI = 1.17-2.82) for psoriatic patient with arthritis. In addition, psoriatic patients without arthritis who had methotrexate treatment showed reduced risks for incident cerebrovascular disease as compared with those with no arthritis and had received no methotrexate/retinoid treatment. Similar analyses were performed on cardiovascular diseases, and equivalent results were obtained. CONCLUSION: Our study indicated that arthritis is a potential determinant for psoriatic patients in terms of incident vascular comorbidities. In addition, methotrexate treatment may be associated with reduced risks for development of severe vascular diseases in psoriatic patients without arthritis. Further studies should focus on the clinical complications associated with psoriatic patients with or without arthritis.

Lymphopaenia, anti-Ro/anti-RNP autoantibodies, renal involvement and cyclophosphamide use correlate with increased risk of herpes zoster in patients with systemic lupus erythematosus.

Herpes zoster occurs with increased frequency in patients with systemic lupus erythematosus (SLE). The aim of this study was to identify and evaluate clinical and laboratory risk factors associated with development of herpes zoster in patients with SLE. A retrospective case-control study was performed in a population of patients with SLE. Patients were identified as cases if their first episode of herpes zoster occurred after diagnosis of SLE. Patients with SLE who never developed herpes zoster were enrolled as controls. Medical charts and laboratory data for both cases and control patients were comprehensively reviewed. A total of 65 cases and 105 controls were included. Risk factors associated with the development of herpes zoster in patients with SLE were found to be lymphopaenia, anti-Ro antibodies, anti-RNP antibodies, neuropsychiatric manifestations, renal involvement and cyclophosphamide use. Therefore, the presence of certain disease manifestations in patients with SLE represents risk factors for the development of herpes zoster.

Association between non-atopic hand eczema and interleukin-13 gene polymorphism in Taiwanese nursing population.

Chronic hand eczema is an important occupational skin disease with atopic dermatitis (AD) and wet work being the most important risk factors. This study was launched to analyse the potential association between AD-related inflammation genes and development of non-atopic hand eczema among nurses in University Hospital. Atopic eczema, non-atopic hand dermatitis and control groups were identified. The association between occurrence of non-atopic hand eczema and interleukin (IL)-13, IL-4 and IL-5 gene variants was analysed. IL13 rs20541 A allele [assuming recessive model; odds ratio (OR) = 3.38, 95% CI: (1.63-7.00)] showed association with development of non-atopic hand eczema. Additive score analyses showed combination of this gene variant with previously identified risk factors including certain SPINK5 polymorphism and more than 10 years of work experience conferred highest risk for development of non-atopic hand eczema. As non-atopic hand eczema made up significant portion of occupational skin diseases, further studies should be focused on this commonly encountered skin condition.

Psoriatic patients with diabetes are prone to develop digestive organ cancers: a population-based study in Taiwan.

BACKGROUND: Psoriasis is an inflammatory skin condition. Epidemiology studies from different parts of the world have shown that psoriasis is associated with different components of metabolic syndrome. The association between psoriasis and development of cancer has not yet been clearly established. OBJECTIVE: We hypothesize that chronic inflammation is the driving force that enhances the risk of malignancy in psoriatic patients and suspect that psoriatic patients have higher risks for developing cancers that are most prevalent in the studied population. METHODS: Using the nested case-control approach derived from the Taiwanese population-based cohort, the current study was launched to validate this hypothesis. Results 8180 psoriatic patients and 163,600 age-matched controls were included in this study. Psoriatic patients were 1.20 folds (95% CI=1.06-1.36; p=0.004) more likely than controls to develop cancer. Further analyses revealed that incident cancers derived from digestive tract, the most common cancer origin found in Taiwanese population, were most significantly associated psoriasis. Patients with psoriasis and diabetes mellitus, a frequent comorbid condition independently associate with both psoriasis and cancer, conferred the highest risk for developing digestive tract cancers, having risks of 1.98 folds (95% CI: 1.11-3.52) and 1.68 folds (95%CI: 1.23-2.28) for the 41-60 years-old and 61-80 years-old age group, respectively. Both psoriasis and diabetes were independently associated with development of digestive tract cancers in the 41-60 years-old patient group. CONCLUSION: Prevalent cancers in the population should be carefully monitored in the psoriatic patients after middle age (beyond 40 years of age) especially for those with concomitant diabetic conditions.

Methotrexate reduces the occurrence of cerebrovascular events among Taiwanese psoriatic patients: a nationwide population-based study.

Psoriasis is a chronic inflammatory disease. The aim of this study was to evaluate the effects of methotrexate and retinoid on risks for developing cerebrovascular disease among psoriatic patients. A population-based nested case-control study was conducted using the Taiwanese National Health Insurance database. Cox proportional hazards models were adopted. The hazard ratio (HR) of newly developed cerebrovascular disease was 1.28 (95% confidence interval (CI) = 1.162-1.413; p < 0.0001) for psoriatic vs. non-psoriatic subjects. In terms of the effects of methotrexate or retinoid on the occurrence of cerebrovascular disease, a significant protection effect (HR = 0.50; 95% CI = 0.27-0.92; p = 0.0264) was found for patients with methotrexate prescription. Retinoid prescription showed no protective effect. Further analyses revealed that a low cumulative methotrexate dose is associated with significant protective effect (HR = 0.53; 95% CI = 0.28-1.00; p = 0.0486) while a high cumulative dose was not (HR 0.80; 95% CI = 0.11-5.68; p = 0.8214). These results suggest that psoriatic patients receiving low-dose methotrexate treatment may have reduced risk for developing cerebrovascular disease. Further prospective study should be performed to validate the vasculoprotective effect of this treatment strategy.

Distinct SPINK5 and IL-31 polymorphisms are associated with atopic eczema and non-atopic hand dermatitis in Taiwanese nursing population.

The term 'hand dermatitis' describes inflammatory skin condition localized to the hands. Nurses working at hospital settings are prone to develop hand dermatitis. The current study aimed to evaluate whether certain genetic polymorphisms were associated with the development of atopic eczema or non-atopic hand dermatitis in Taiwanese population. Nurses of Kaohsiung Medical University Hospital were recruited. Atopic eczema, non-atopic hand dermatitis and normal control groups were identified. The serine protease inhibitor Kazal type 5 (SPINK5), filaggrin and interleukin-31 (IL-31) gene variants were compared between the diseased and control groups. Our results showed that rs2303070 T allele of SPINK5 (assuming recessive model; OR=3.58, 95% CI 1.63-7.84; P=0.0014) and rs7977932 G allele of IL-31 (assuming recessive model; OR=18.25, 95% CI =3.27-101.94; P=0.0009) were associated with increased risks of developing atopic eczema, while rs6892205 G allele of SPINK5 (assuming dominant model; OR=3.79, 95% CI 1.55-9.28; P=0.0036) was associated with the development of non-atopic hand dermatitis. In summary, our results showed that distinct SPINK5 and IL-31 gene variants were associated with the development of atopic eczema and non-atopic hand dermatitis. The barrier function, particularly those regulated by SPINK5, may play an important role in the development of both atopic eczema and non-atopic hand dermatitis.

Hand dermatitis among university hospital nursing staff with or without atopic eczema: assessment of risk factors.

BACKGROUND: Nurses are prone to develop hand dermatitis. Although an atopic constitution has been identified as a genetic risk factor, the behavioural risk factors associated with hand dermatitis in wet work conditions have not been fully explored. OBJECTIVES: This study aimed to clarify the impact of atopic eczema (fulfilling the diagnostic criteria during the past 1 year) on the occurrence of hand dermatitis and to identify the behavioural risk factors among non-atopic nurses with hand dermatitis. METHODS: From August 2007 to July 2009, nurses from Kaohsiung Medical University Hospital were recruited. The associations between different risk factors and hand dermatitis were documented. In addition, the behavioural risk factors among non-atopic nurses were evaluated via observational study. RESULTS: One thousand one hundred and thirty-two nurses participated in the first part of the study, which revealed that individuals with atopic eczema had a 3.76-fold increased risk for hand dermatitis. However, among 248 nurses with hand dermatitis, only 43 had atopic eczema. The observational study performed on 140 non-atopic nurses identified frequency of hand washing as the behavioural risk factor associated with hand dermatitis. CONCLUSIONS: Although atopic eczema is the major risk factor for hand dermatitis, those with atopic eczema constitute only 17% of nurses with hand dermatitis. Decreasing hand washing frequency is the most effective strategy to reduce the occurrence of hand dermatitis among non-atopic nurses.

Prevalence of adult atopic dermatitis among nursing staff in a Taiwanese medical center: a pilot study on validation of diagnostic questionnaires.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing dermatosis. Previous studies have focused mostly on pediatric patients, and investigations emphasizing adult AD have been limited. OBJECTIVE: We set out to determine the 1-year prevalence and evaluate the validity of the International Study of Asthma and Allergies in Childhood (ISAAC) and United Kingdom Working Party (UKWP) AD questionnaires of adult AD in Taiwan. METHODS: We conducted a cross-sectional study among nursing staff at a university hospital. The 1-year prevalence of AD was assessed by ISAAC and UKWP questionnaires. Subsequently, the dermatologists' diagnosis based on Hanifin and Rajka criteria was used as a reference for validation. RESULTS: The overall response rate was 92.9%, equivalent to 1131 complete questionnaires. Ninety adult patients with AD (8%) were identified by dermatologists' diagnosis whereas ISAAC identified 107 (9.5%); sensitivity and specificity were 36.7% and 92.9%, respectively. UKWP identified 42 (3.7%) patients with AD; sensitivity and specificity were 42.2% and 99.6%, respectively. Using the receiver operating characteristic curve analysis, the UKWP criteria performed significantly better than its ISAAC counterpart. Further analysis indicated that modification of these criteria resulted in significant improvement in their diagnostic efficacy. More specifically, modified ISAAC showed 90.0% and 55.2% sensitivity and specificity, respectively, whereas modified UKWP demonstrated 82.2% and 94.2% sensitivity and specificity, respectively. LIMITATION: Most of the study subjects were female with a high educational background. CONCLUSION: Currently available questionnaire instruments do not perform well in the identification of adult patients with AD. Modification of the original questionnaires may allow for future large-scale epidemiologic studies.

The effect of preoperative transarterial chemoembolization of resectable hepatocellular carcinoma on clinical and economic outcomes.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant cancers in the world. The effect of preoperative transarterial chemoembolization (TACE) for resectable HCC is still controversial and cost-associated treatments are unknown. METHODS: We retrospectively compared clinical outcomes and resource utilization after liver resection between patients who underwent preoperative TACE (TACE-LR group, n = 114) and those who did not (LR group, n = 236). RESULTS: The overall mortality rate was 27.54% for the LR group versus 39.47% for the TACE-LR group (P < 0.05). The overall recurrent rates were 29.36% for the LR group versus 35.90% for the TACE-LR group (P > 0.05). Multivariate Cox regression analysis showed that preoperative TACE was a significant risk factor (P = 0.002, HR = 1.995, 95% CI 1.297-3.069) for overall long-term survival for HCC. The TACE-LR group had longer mean lengths of stay and higher hospital charges, both at index hospitalization and at 6 months for follow-up. CONCLUSION: Preoperative TACE is not only associated with higher medical utilizations, but it is also correlated with higher mortality rates over a 5-year period. The preoperative TACE does not benefit patients with resectable HCC. The golden standard or clinical guidelines should be developed to provide better clinical decisions and decision support for HCC patients.

Hand eczema among University Hospital nursing staff: identification of high-risk sector and impact on quality of life.

BACKGROUND: Hand eczema is a commonly encountered occupational disease and has a negative impact on life quality. OBJECTIVE: This study aimed to identify the specific conditions that may pose a higher risk for occurrence of hand eczema and evaluate the impact of hand eczema on life quality. METHOD: Nursing staff from a university hospital were invited to participate in a cross-sectional study. Validated questionnaires for hand eczema and life quality were used to evaluate the point prevalence and determine the impacts of hand eczema, respectively. RESULTS: The overall response rate was 93%, equivalent to 1132 completed questionnaires. Two hundred and forty-eight (22%) reported occurrence of hand eczema. Occurrence of hand eczema was significantly associated with nursing for >10 years and working in a special care unit, with prevalences of 27% and 26%, respectively. In addition, hand eczema was associated with suboptimal life quality; pruritus or burning sensations were associated with a lower quality of life among those with hand eczema. CONCLUSION: Hand eczema is a work-related problem for nursing staff; proper preventive programmes should be implemented for those nursing staff working in high-risk areas to avoid further lowering of their quality of life.

The spliced variant of hepatitis B virus protein, HBSP, interacts with Bcl-2/Bcl-xl in vitro and induces apoptosis in HepG2 cells.

We have recently reported that the naturally occurring spliced variant of Hepatitis B virus protein, HBSP, displayed proapoptotic activity through its BH3 domain. To investigate whether the BH3 domain in HBSP interacted with Bcl-2 family of proteins, HBSP and Bcl-2 family of proteins were cloned and expressed in our mammalian two-hybrid system. Interaction assays were carried out in HepG2 cells and measured by the activity of the reporter gene product luciferase. Our results indicated that HBSP interacted with Bcl-2/Bcl-xl in vitro and induced apoptosis in HepG2 cells.

Molecular biology changes associated with LRRK2 mutations in Parkinson's disease.

Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal loss in the substantia nigra. The recent discovery of leucine-rich-repeat kinase 2 gene (LRRK2) mutations in PD is significant because these mutations are the most common cause of autosomal dominant PD. Furthermore, a common recurrent mutation (G2019S) is associated with a significant proportion of nonfamilial PD, and a polymorphic variant (G2385R) has been found to increase the risk in the Asian race. The large LRRK2 protein of 280 kD contains three protein-protein interaction domains and two enzymatic domains, the Ras-related GTPase and the kinase. Mutations in these domains have been described in PD patients. Preliminary evidence suggests that some types of LRRK2 mutations increase the kinase activity, and this is associated with significantly higher apoptotic cell death in dopaminergic cell lines and primary neurons; abolishing the kinase function ameliorates this cellular toxicity. It also appears that its GTPase domain can be activated independently, whereas the kinase activity strictly requires the GTPase activation. Mutations in the LRRK2 have displayed notable pleomorphic pathologies that might indicate an upstream role of LRRK2 in cellular signaling pathways. The identification of physiological substrates (likely to be involved in signaling and apoptotic pathways) of LRRK2 remains an important step in our understanding of the role of LRRK2 in the disease process. Further in vitro and in vivo studies will unravel the role of LRRK2 in cell signaling and its impact on proliferation, differentiation, and survival of neurons.

Cellular apoptosis induced by replication of hepatitis B virus: possible link between viral genotype and clinical outcome.

HBV remains one of the major pathogens of liver diseases but the outcomes as inflammation, cirrhosis and cancer of the liver are greatly related to different viral genotypes. The aim of this study was to assess the pro-apoptotic effect of HBSP from three HBV genotypes on liver derived cells. HepG2 cells were applied in our system and transfected by HBV genotype A, B, and C. Cells were observed under phase contrast microscope, stained by apoptosis marker and analyzed by flow cytometry. HBSP expression was detected by western blot assay. BH3 sequences were aligned and analyzed by Vector NTI. HBV genotypes A, B, and C transfected cells displayed evidence of cell death which was further proved as apoptosis. Natural expression of a pro-apoptotic protein HBSP was detected during genomes transfection. The different apoptotic effects were correlated to the HBSP expression from each genome. Alignment and analysis of the BH3 domains from the three genomes revealed slight variance which might also contribute to the result. Our results suggested that variant HBSP expression and BH3 sequence of HBV genotypes may be involved in differential apoptotic effect in transfected cells. Detailed analysis of the role of HBV genotypes in cellular apoptotic process should provide molecular information on the reported clinical outcome of infection by different HBV genotypes.