Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations. METHODS: Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI. RESULTS: Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments. CONCLUSION: According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Health-related quality of life among cancer survivors: pre-existing chronic conditions are to be given priority.

PURPOSE: This study aimed to describe the health-related quality of life (HRQoL) of cancer survivors in China by the five-level EuroQol-5-dimension (EQ-5D-5L) questionnaire and to explore the impact of the comorbidity of pre-existing chronic conditions on HRQoL in cancer survivors. METHODS: Data on cancer survivors were obtained from two cross-sectional surveys conducted in Shandong Province, China. The data of the Chinese general population, the Chinese diabetes population, the Chinese hypertension population, and the Chinese urban population from the published studies were used as the controls. The χ2 test was conducted to compare the incidence of five-dimensional problems between the study and control populations. The non-parametric Mann-Whitney U test and Kruskal-Wallis test were performed to examine the differences in EQ-5D-5L utility scores. Besides, the Tobit regression model was used to examine the variables influencing the EQ-5D-5L utility score. RESULTS: One thousand fifty-one adult cancer survivors were included. Cancer survivors had significantly lower EQ-5D-5L utility scores (Z = - 15.939, P < 0.001) and EQ-VAS scores (Z = - 11.156, P < 0.001) than the general adult population. The average EQ-5D-5L utility score of hypertensive cancer survivors was lower than that of the hypertensive population (Z = - 1.610, P = 0.107), but the difference was not statistically significant. CONCLUSION: Compared to the general population, the HRQoL of cancer survivors was extremely poor in all dimensions of the EQ-5D-5L. Pre-existing chronic conditions had significant antecedent effects on the HRQoL of cancer survivors. Therefore, more attention should be paid to chronic diseases, and effective interventions should be adopted based on this.

Associations between cold spells of different time types and coronary heart disease severity.

Limited evidence showed the association between cold spells and the severity of coronary heart disease (CHD). This study was to investigate the association between cold spells with their different time types and CHD severity. We collected data on CHD patients admitted to the Zhongnan Hospital, Wuhan, China from 2016 to 2021. CHD severity was quantified using the SYNTAX score and transformed into a binomial variable. Daily mean, maximum and minimum temperature were collected during the study period. We first used daily mean temperature to find the optimum definition among multiple thresholds and durations. The daily maximum and minimum temperatures were used to define different types of cold spells (daytime, nighttime and compound) based on the optimum definition. Annual cold spell days were included to assess individual exposure to cold spells. Logistic regression models were performed to fit the association between cold spell days and CHD severity stratified by different tertiles of PM2.5 and NDVI. In this study, 1937 CHD patients were included. The cold spell defined as at least four consecutive days with daily mean temperature below the 5th percentile exhibited the optimum model. We found that a 4-day increase in cold spell days was associated with more severe CHD (OR = 1.170, 95% CI: 1.074, 1.282). Such an association was more pronounced under higher levels of PM2.5 by OR = 1.270 (1.086, 1.494) and lower levels of greenness by OR = 1.240 (1.044, 1.476). Compared with daytime and compound cold spells, nighttime cold spells showed the strongest association with CHD severity by OR = 1.141 (1.026, 1.269). This study showed that exposure to cold spells was positively associated with CHD severity, especially the nighttime cold spells. The association between cold spells and CHD severity was more significant in high levels of PM2.5 and low levels of greenness.

Mechanistic Insights into the Halophilic Xylosidase Xylo-1 and Its Role in Xylose Production.

The Xylo-1 xylosidase, which belongs to the GH43 family, exhibits a high salt tolerance. The present study demonstrated that the catalytic activity of Xylo-1 increased by 195% in the presence of 5 M NaCl. Additionally, the half-life of Xylo-1 increased 25.9-fold in the presence of 1 M NaCl. Through comprehensive analysis including circular dichroism, fluorescence spectroscopy, and molecular dynamics simulations, we elucidated that the presence of Na+ ions increased the contact frequency between the surface acidic amino acids and the surrounding water molecules. This resulted in the stabilization of the surrounding hydration layer of Xylo-1. Additionally, Na+ ions also stabilized the substrate-binding conformation and the fluctuation of water molecules within the active site, which enhanced the catalytic activity of Xylo-1 by increasing the nucleophilic attack by the water molecules. Ultimately, the optimal reaction conditions for the production of xylose by synergistic catalysis with Xylo-1 and xylanase were determined. The results demonstrated that the conversion yield of the method was high for various sources of xylan, indicating the method could have potential industrial applications. This study explored the structure-activity relationship of catalysis in Xylo-1 under high-salt conditions, provides novel insights into the mechanism of halophilic enzymes, and serves as a reference for the industrial application of Xylo-1.

Association Between Online Health Information-Seeking Behaviors by Caregivers and Delays in Pediatric Cancer: Mixed Methods Study in China.

BACKGROUND: Pediatric cancer patients in China often present at an advanced stage of disease resulting in lower survival and poorer health outcomes. One factor hypothesized to contribute to delays in pediatric cancer has been the online health information-seeking (OHIS) behaviors by caregivers. OBJECTIVE: This study aims to examine the association between OHIS behaviors by caregivers and delays for Chinese pediatric cancer patients using a mixed methods approach. METHODS: This study used a mixed methods approach, specifically a sequential explanatory design. OHIS behavior by the caregiver was defined as the way caregivers access information relevant to their children's health via the Internet. Delays in pediatric cancer were defined as any one of the following 3 types of delay: patient delay, diagnosis delay, or treatment delay. The quantitative analysis methods included descriptive analyses, Student t tests, Pearson chi-square test, and binary logistic regression analysis, all performed using Stata. The qualitative analysis methods included conceptual content analysis and the Colaizzi method. RESULTS: A total of 303 pediatric cancer patient-caregiver dyads was included in the quantitative survey, and 29 caregivers completed the qualitative interview. Quantitative analysis results revealed that nearly one-half (151/303, 49.8%) of patients experienced delays in pediatric cancer, and the primary type of delay was diagnosis delay (113/303, 37.3%), followed by patient delay (50/303, 16.5%) and treatment delay (24/303, 7.9%). In this study, 232 of the 303 (76.6%) caregiver participants demonstrated OHIS behaviors. When those engaged in OHIS behaviors were compared with their counterparts, the likelihood of patient delay more than doubled (odds ratio=2.21; 95% CI 1.03-4.75). Qualitative analysis results showed that caregivers' OHIS behaviors impacted the cancer care pathway by influencing caregivers' symptom appraisal before the first medical contact and caregivers' acceptance of health care providers' diagnostic and treatment decisions. CONCLUSIONS: Our findings suggest that OHIS among Chinese pediatric caregivers may be a risk factor for increasing the likelihood of patient delay. Our government and society should make a concerted effort to regulate online health information and improve its quality. Specialized freemium consultations provided by health care providers via online health informatic platforms are needed to shorten the time for caregivers' cancer symptom appraisal before the first medical contact.

The atherogenic index of plasma (AIP) is a predictor for the severity of coronary artery disease.

Objective: Dyslipidemia is a key risk factor for coronary artery disease (CAD). This study aimed to investigate the correlation between the atherogenic index of plasma (AIP) and the severity of CAD. Methods: 2,491 patients were enrolled in this study and analyzed retrospectively, including 665 non-CAD patients as the control group and 1,826 CAD patients. The CAD patients were classified into three subgroups according to tertiles of SYNTAX score (SS). Non-high-density lipoprotein cholesterol (Non-HDL-C) was defined as serum total cholesterol (TC) minus serum high-density lipoprotein cholesterol (Non-HDL-C), atherogenic index (AI) was defined as the ratio of non-HDL-C to HDL-C; AIP was defined as the logarithm of the ratio of the concentration of triglyceride (TG) to HDL-C; lipoprotein combine index (LCI) was defined as the ratio of TC∗TG∗ low-density lipoprotein cholesterol (LDL)to HDL-C; Castelli Risk Index I (CRI I) was defined as the ratio of TC to HDL-C; Castelli Risk Index II (CRI II) was defined as the ratio of LDL-C to HDL-C. Results: The levels of AIP (P < 0.001), AI (P < 0.001), and LCI (P = 0.013) were higher in the CAD group compared with the non-CAD group. The Spearman correlation analysis showed that AIP (r = 0.075, P < 0.001), AI (r = 0.132, P < 0.001), and LCI (r = 0.072, P = 0.001) were positively correlated with SS. The multivariate logistic regression model showed CRI I (OR: 1.11, 95% CI: 1.03-1.19, P = 0.005), CRI II (OR: 1.26, 95% CI: 1.15-1.39, P < 0.001), AI (OR: 1.28, 95% CI: 1.17-1.40, P < 0.001), AIP (OR: 2.06, 95% CI: 1.38-3.07, P < 0.001), and LCI (OR: 1.01, 95% CI: 1.01-1.02, P < 0.001) were independent predictors of severity of CAD After adjusting various confounders. Conclusion: CRI I, CRI II, AIP, AI, and LCI were independent predictors of the severity of CAD, which could be used as a biomarker for the evaluation of the severity of CAD.

Prevalence of Low-Frequency, Antiviral Resistance Variants in SARS-CoV-2 Isolates in Ontario, Canada, 2020-2023.

Importance: Nirmatrelvir-ritonavir is an oral antiviral medication that improves outcomes in SARS-CoV-2 infections. However, there is concern that antiviral resistance will develop and that these viruses could be selected for after treatment. Objective: To determine the prevalence of low-frequency SARS-CoV-2 variants in patient samples that could be selected for by nirmatrelvir-ritonavir. Design, Setting, and Participants: This retrospective cohort study was conducted at 4 laboratories that serve community hospitals, academic tertiary care centers, and COVID-19 assessment centers in Ontario, Canada. Participants included symptomatic or asymptomatic patients who tested positive for SARS-CoV-2 virus and submitted virus samples for diagnostic testing between March 2020 and January 2023. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: Samples with sufficient viral load underwent next-generation genome sequencing to identify low-frequency antiviral resistance variants that could not be identified through conventional sequencing. Results: This study included 78 866 clinical samples with next-generation whole-genome sequencing data for SARS-CoV-2. Low-frequency variants in the viral nsp5 gene were identified in 128 isolates (0.16%), and no single variant associated with antiviral resistance was predominate. Conclusions and Relevance: This cohort study of low-frequency variants resistant to nirmatrelvir-ritonavir found that these variants were very rare in samples from patients with SARS-CoV-2, suggesting that selection of these variants by nirmatrelvir-ritonavir following the initiation of treatment may also be rare. Surveillance efforts that involve sequencing of viral isolates should continue to monitor for novel resistance variants as nirmatrelvir-ritonavir is used more broadly.

Heterogeneous Waterborne Polyurethane Composite with Alternating Electromagnetic Layers for Absorption-Dominated Electromagnetic Interference Shielding.

Flexible waterborne polyurethane (WPU) electromagnetic interference (EMI) composites of heterogeneous alternating multilayer structure with conductive gradient were fabricated through the layer-by-layer stacking and hot-pressing methods. Combining the synergetic electromagnetic loss and interface polarization loss formed by the selective distribution of metallized chopped polyimide fiber (PI@Ni/Cu/Ni), reduced graphene oxide (rGO), and magnetic Fe3O4 fillers, as well as multilevel electromagnetic wave propagation paths, the penetrating microwaves would undergo a particular "absorption-reflection-reabsorption" process in the composite. The asymmetric multilayer WPU composite with an absorption-dominated shielding feature exhibits a high EMI shielding effectiveness (SE) of 53.90 dB and an A value of 0.56. Moreover, the multilayer WPU composite maintains excellent integrity through repeating bending, long-time soaking, and burning tests. This work provides a viable strategy for the design of absorption-dominated EMI shielding material with controllable and stable performance that is befitting for next-generation advanced electronic products.

Multi-hierarchically Structural Polycaprolactone Composites with Tunable Electromagnetic Gradients for Absorption-Dominated Electromagnetic Interference Shielding.

Achieving absorption-dominated electromagnetic interference (EMI) shielding composites with high shielding effectiveness (SE) remains a great challenge due to their minimization of secondary EM radiation pollution, which is highly desired for next-generation electronic devices. Herein, an ingenious approach is proposed to develop asymmetric hierarchical polycaprolactone (PCL) composites composed of an impedance matching layer and a conductive layer through the combination of alternate casting and electroless plating methods, while the polarization loss caused by the difference in conductivity between the two layers would further attenuate the EM waves. The gradient distribution of the shielding fillers creates a positive conductive gradient and a negative magnetic gradient; the higher the gradient, the more it induces magnetic and dielectric losses, which results in an enhanced absorption mechanism that could overcome the restrictions of the nonadjustable reflective properties. The obtained Fe3O4@rGO/Ni/Ag/PCL composite possesses a remarkable EMI SE of 47.6 dB, while the power coefficient of reflectivity (R) could be significantly reduced to 0.27. This research provides a feasible strategy for developing absorption-dominated shielding materials with tunable EM performance that are appropriate for the next generation of electronic devices.

Comparison of the value of various complex indexes of blood cell types and lipid levels in coronary heart disease.

Background: Inflammation and lipid infiltration play crucial roles in the development of atherosclerosis. This study aimed to investigate the association between various complex indexes of blood cell types and lipid levels with the severity of coronary artery stenosis and their predictive value in coronary heart disease (CHD). Methods: The retrospective study was conducted on 3,201 patients who underwent coronary angiography at the Department of Zhongnan Hospital of Wuhan University. The patients were divided into two groups: CHD group and non-CHD group. The CHD group was further classified into three subgroups (mild, moderate, severe) based on the tertiles of their Gensini score or SYNTAX score I. Various complex indexes of blood cell types and lipid levels were compared between the groups. Results: It revealed a positive correlation between all complex indexes and the severity of coronary artery stenosis. The systemic inflammation-response index/high-density lipoprotein cholesterol count (SIRI/HDL) exhibited the strongest correlation with both severity scores (Gensini score: r = 0.257, P < 0.001; SYNTAX score I: r = 0.171, P < 0.001). The monocyte to high-density lipoprotein cholesterol ratio (MHR) was identified as a stronger independent risk factor for CHD. However, SIRI/HDL had higher diagnostic efficacy for CHD (sensitivity 66.7%, specificity 60.4%, area under curve 0.680, 95% CI: 0.658-0.701). Notably, the pan-immune-inflammation value multiplied by low-density lipoprotein cholesterol count (PIV × LDL) exhibited the highest sensitivity of 85.2%. Conclusion: All complex indexes which we investigated exhibited positive correlations with the severity of coronary artery stenosis. SIRI/HDL demonstrated higher diagnostic efficiency for CHD and a significant correlation with the severity of coronary artery stenosis.

A Slippery Liquid-Infused Network-like Surface with Anti/De-icing Properties Constructed Based on the Phosphating Reaction.

The excessive accumulation of ice seriously threatens various industrial facilities and production activities. Currently, slippery liquid-injected porous surfaces (SLIPS) have been developed as a new strategy for anti/de-icing; however, the lack of research on the adsorption and storage capacity for lubricating fluids has limited the development of SLIPS in the anti/de-icing field to some extent. In this work, a slippery liquid-infused phosphate network-like surface (SLIPNS) is prepared that adjusts the texture of the surface by varying the phosphating time to control the adsorption and storage of lubricating fluids. The as-obtained surface structure gives the SLIPNS excellent oil-storage/locked properties, can delay the freezing time of sessile droplets up to 436 s, which is almost 10 times that of an untreated aluminum sheet, and exhibits one-tenth the ice adhesion strength of untreated aluminum substrates (14.39 kPa). In addition, the SLIPNS shows effective durability and antifouling ability and has great potential in solving long-term anti/de-icing problems.

The optimal timing for non-culprit percutaneous coronary intervention in patients with multivessel coronary artery disease: A pairwise and network meta-analysis of randomized trials.

Background and aims: Recently, several randomized trials have shown that patients with multivessel disease (MVD) often pursue complete revascularization during percutaneous coronary intervention (PCI) to improve their prognosis. However, the optimal time for the non-culprit artery has been controversial. This study aimed to determine the optimal strategy for revascularization in ST-segment elevation myocardial infarction (STEMI) patients with multivessel coronary artery disease (CAD). Methods: Randomized controlled trials (RCTs) comparing three revascularization strategies [i.e., complete revascularization at the index procedure (CR), complete revascularization as a staged procedure (SR), or culprit-only revascularization (COR)] in STEMI patients with multivessel coronary artery disease were included. We performed both pairwise and network meta-analyses. Network meta-analysis was performed using mixed treatment comparison models. Results: 17 trials with 8568 patients were included. In the network meta-analysis, the most interesting finding was that staged revascularization increased the risk of major adverse cardiac events (MACE) compared with complete revascularization at the index procedure [odds ratio (OR): 1.93; 95% confidence interval (CI): 1.07-3.49]. In the pairwise meta-analysis, complete revascularization reduced the incidence of MACE [risk ratio (RR): 0.62, 95% CI: 0.48-0.79, p < 0.001], mainly because it reduced the probability of unplanned repeat revascularization (RR: 0.49, 95% CI: 0.33-0.75, p = 0.001). There were no significant differences in all-cause mortality, cardiac mortality, or nonfatal re-myocardial infarction (MI). Conclusion: Our analysis suggests that complete revascularization should be performed in STEMI patients with multivessel coronary artery disease, and complete revascularization at the index procedure is superior to staged revascularization in reducing the risk of MACE events.

Combination of Universal Chemical Deposition and Unique Liquid Etching for the Design of Superhydrophobic Aramid Paper with Bioinspired Multiscale Hierarchical Dendritic Structure.

It is urgent and significant for the further development of superhydrophobic materials to exploit a facile, low-cost, scalable, and eco-friendly method for the manufacture of superhydrophobic materials with self-cleaning, antifouling, directional transportation, and other characteristics. Herein, an outstanding superhydrophobic material composed of a flexible microconvex aramid paper substrate, micron-scale cone-shaped copper, micro-nanoscale dendritic copper oxide, and hydrophobic copper stearate film has been successfully constructed through delicate architectural design and a convenient preparation approach. Based on the microstructure evolution and composition analysis results, it is revealed that the cone-shaped copper was etched into a dendritic copper oxide structure step by step from the top to bottom and from the outside to inside in an alkaline liquid environment. Moreover, by virtue of the compositional features and structural characteristics, the constructed superhydrophobic material showcased a high contact angle (CA), low sliding angle (SA), high porosity, low surface free energy, and adhesion work. Meanwhile, the dendritic microstructure analysis, the calculation of solid-liquid interfacial tension, and the force analysis of water droplets jointly revealed the mechanism of the bounce and merged bounce of water droplets. Finally, this superhydrophobic material has the functions of self-cleaning, antifouling, and directional transportation, especially by controlling the deformation of the material to realize the transportation of water droplets in a specified direction.

Clinical Value and Role of miR-129-5p in Non-Alcoholic Fatty Liver Disease.

This study was to evaluate the expression of miR-129-5p in non-alcoholic fatty liver (NAFLD) patients and its clinical value and explore its regulatory effect on insulin resistance (IR). A total of 117 NAFLD patients and 110 healthy controls were included. The levels of miR-129-5p were detected by qRT-PCR. To assess the diagnostic value of miR-129-5p for NAFLD, the receiver operating characteristic curve (ROC) was established. C57Bl/6 mice were supplied with high-fat diet to establish NAFLD model. Intraperitoneal insulin tolerance test (IPITT) was carried out to evaluate the effect of miR-129-5p on IR in NAFLD animal model. miR-129-5p was highly expressed in the serum of NAFLD patients, and patients with HOMA-IR ≥2.5 had higher level of miR-129-5p than those with HOMA-IR <2.5. miR-129-5p had the ability to differentiate NAFLD patients from healthy individuals and might be associated with the development of IR. Serum miR-129-5p was positively correlated with the levels of HOMA-IR, BMI, total cholesterol (TC), and triglyceride (TG) in NAFLD patients. Downregulation of miR-129-5p regulates lipid metabolism and insulin sensitivity in NAFLD mice model. MiR-129-5p was upregulated in NAFLD patients and might be a potential diagnostic biomarker. The regulatory effect of miR-129-5p on NAFLD may function by regulating lipid accumulation and insulin sensitivity.

Whole-exome sequencing identifies susceptibility genes and pathways for idiopathic pulmonary fibrosis in the Chinese population.

Genetic factors play a role in the risk of idiopathic pulmonary fibrosis (IPF). Specifically, MUC5B rs35705950 non-risk alleles and immunologic aberrations were associated with the IPF's progression. However, rare genetic variants have not been systematically investigated in Chinese IPF patients. In this study, we aimed to improve understanding of the genetic architecture of IPF in the Chinese population and to assess whether rare protein-coding variants in the immunity pathway genes are enriched in the IPF patients with non-risk alleles at rs35705950. A case-control exome-wide study including 110 IPF patients and 60 matched healthy controls was conducted. rs35705950 was genotyped by Sanger sequencing. To identify genes enriched in IPF, gene-based association analyses were performed. Identified genes were included for further pathway analyses using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Associations between rs35705950 and genes enriched in the immunity pathway were also tested. 226 genes that were enriched with deleterious variants were identified in IPF patients. Out of them, 36 genes were significantly enriched in GO and KEGG pathways in the IPF. Pathway analyses implicated that these genes were involved in the immune response and cell adhesion. Rare protein-altering variants in genes related to the immunity pathway did not significantly differ between patients with a MUC5B risk allele and individuals without risk allele. We drafted a comprehensive mutational landscape of rare protein-coding variants in the Chinese IPF and identified genes related to immune response and cell adhesion. These results partially explain changes in gene expression involved in the immunity/inflammatory pathways in IPF patients.

Tolerance and response of two honeybee species Apis cerana and Apis mellifera to high temperature and relative humidity.

The ambient temperature and relative humidity affect the metabolic and physiological responses of bees, thus affecting their life activities. However, the physiological changes in bee due to high temperature and high humidity remain poorly understood. In this study, we explored the effects of higher temperature and humidity on the epiphysiology of bees by evaluating the survival, tolerance and body water loss in two bee species (Apis cerana and Apis mellifera). We also evaluated the changes in the activity of antioxidant and detoxification enzymes in their body. We observed that under higher temperature and humidity conditions, the survival rate of A. mellifera was higher than that of A. cerana. On the other hand, a comparison of water loss between the two species revealed that A. mellifera lost more water. However, under extremely high temperature conditions, A. cerana was more tolerant than A. mellifera. Moreover, under higher temperature and humidity conditions, the activity of antioxidant and detoxification enzymes in bees was significantly increased. Overall, these results suggest that high temperatures can adversely affect bees. They not only affect the survival and water loss, but also stimulate oxidative stress in bees. However, unlike our previous understanding, high humidity can also adversely affect bees, although its effects are lower than that of temperature.

Four novel biomarkers for bladder cancer identified by weighted gene coexpression network analysis.

Bladder cancer (BC) is one of the most malignancies in terms of incidence and recurrence worldwide. The aim of this study is to find out novel and prognostic biomarkers for patients with BC. First, we identified 258 differentially expressed genes by using GSE19915 from Gene Expression Omnibus database. Second, a total of 33 modules were identified by constructing a coexpression network by using weighted gene coexpression network analysis and yellow module was regarded as the key module. Furthermore, by constructing protein-protein interaction networks, we preliminarily picked out 13 genes. Among them, four hub genes (CCNB1, KIF4A, TPX2, and TRIP13) were eventually identified by using five different methods (survival analysis, one-way analysis of variance, the Spearman correlation analysis, receiver operating characteristic curve, and expression value comparison), which were significantly correlated with the prognosis of BC. The validation of transcriptional and translational levels made sense (based on Oncomine and The Human Protein Atlas database). Moreover, functional enrichment analysis suggested that all the hub genes played crucial roles in chromosome segregation, sister chromatid segregation, nuclear chromosome segregation, mitotic nuclear division, nuclear division, and organelle fission during cell mitosis. In addition, three of the hub genes (KIF4A, TPX2, and TRIP13) might be potential targets of cancer drugs according to the results of the genetical alteration. In conclusion, this study indicates that four hub genes have great predictive value for the prognosis of BC, and may contribute to the exploration of the further and more in-depth research of BC.

[Effect of Hanfangji compound on proliferation of hepatic stellate cells and expressions of TTR, ITIH1 and SERPINF2].

OBJECTIVE: To observe and compare the effects of Hanfangji Compound and IFN-gamma on expressions of transthyretin (TTR) , inter-alpha inhibitor H1 (ITIH1) and serpin peptidase inhibitor clade F member 2 (SERPINF2) of hepatic stellate cells (HSC-T6). METHOD: Hanfangji Compound and IFN-gammaof different concentrations were used in hepatic stellate cell-T6 (HSC-T6) for 48 h. Flow cytometer was used to detect the effects of Hanfangji Compound and IFN-gamma on HSC proliferation. RT-PCR method was adopted to detect mRNA expressions of TFR, ITIH1 and SERPINF2. TTR, ITIH1 and SERPINF2 secretions were detected by ELISA. The protein localizations of TTR, ITIH1 and SERPINF2 were examined by immune fluorescence. The protein expression of TfR and ITIHI were determined by Western blot. RESULT: After Hanfangji Compound and IFN-gamma were adopted in HSC-T6, compared with the control group, the cell proliferation was inhibited obviously (P < 0. 05) , protein expressions of TTR, ITIH1 and SERPINF2 and mRNA expression increased significantly, with certain correlation with concentrations of Hanfangji Compound. The 2. 5 g L-I Hanfangji Compound group was superior to the IFN-gamma group (P <0. 05). CONCLUSION: Hanfangji Compound can inhibit HSC proliferation, upregulated TTR, ITIH1 and SERPINF2 proteins and mRNA expression, which may be one of mechanisms of anti-hepatic fibrosis of Hanfangji Compound.

CpG_MI: a novel approach for identifying functional CpG islands in mammalian genomes.

CpG islands (CGIs) are CpG-rich regions compared to CpG-depleted bulk DNA of mammalian genomes and are generally regarded as the epigenetic regulatory regions in association with unmethylation, promoter activity and histone modifications. Accurate identification of CpG islands with epigenetic regulatory function in bulk genomes is of wide interest. Here, the common features of functional CGIs are identified using an average mutual information method to differentiate functional CGIs from the remaining CGIs. A new approach (CpG mutual information, CpG_MI) was further explored to identify functional CGIs based on the cumulative mutual information of physical distances between two neighboring CpGs. Compared to current approaches, CpG_MI achieved the highest prediction accuracy. This approach also identified new functional CGIs overlapping with gene promoter regions which were missed by other algorithms. Nearly all CGIs identified by CpG_MI overlapped with histone modification marks. CpG_MI could also be used to identify potential functional CGIs in other mammalian genomes, as the CpG dinucleotide contents and cumulative mutual information distributions are almost the same among six mammalian genomes in our analysis. It is a reliable quantitative tool for the identification of functional CGIs from bulk genomes and helps in understanding the relationships between genomic functional elements and epigenomic modifications.