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A growing body of research suggests that short-chain fatty acids (SCFAs), metabolites produced by intestinal symbiotic bacteria that ferment dietary fibers (DFs), play a crucial role in the health status of symbiotes. SCFAs act on a variety of cell types to regulate important biological processes, including host metabolism, intestinal function, and immune function. SCFAs also affect the function and fate of immune cells. This finding provides a new concept in immune metabolism and a better understanding of the regulatory role of SCFAs in the immune system, which impacts the prevention and treatment of disease. The mechanism by which SCFAs induce or regulate the immune response is becoming increasingly clear. This review summarizes the different mechanisms through which SCFAs act in cells. According to the latest research, the regulatory role of SCFAs in the innate immune system, including in NLRP3 inflammasomes, receptors of TLR family members, neutrophils, macrophages, natural killer cells, eosinophils, basophils and innate lymphocyte subsets, is emphasized. The regulatory role of SCFAs in the adaptive immune system, including in T-cell subsets, B cells, and plasma cells, is also highlighted. In addition, we discuss the role that SCFAs play in regulating allergic airway inflammation, colitis, and osteoporosis by influencing the immune system. These findings provide evidence for determining treatment options based on metabolic regulation.

Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P

A major performance index for analyzing a stochastic transport network is the two-terminal capacity reliability Rd, defined as the probability that d units of goods can be successfully transported via stochastic arc capacities from the source to the destination. This paper presents an efficient d-minimal path method to calculate Rd based on some newly obtained results. The proposed method uses a simple method to check d-minimal path candidates and a more efficient approach to remove duplicate d-minimal paths that are the biggest obstacle in solving d-minimal paths, along with an indication of the advantage over the existing methods. Besides, sensitivity analysis is adopted to explore the most important arc whose reliability change affects the network reliability most significantly, which helps supervisor identify and enhance the critical arcs for improving the network reliability more effectively. Computational and application examples demonstrate the efficiency and utility of the method, respectively.

Penile squamous cell carcinoma (PSCC) is a rare malignancy with poor survival after standard treatment. Although genomic alterations of PSCC have been characterized in several latest studies, the association between the formation of somatic landscape and regional lymph node metastasis (LNM), an important predictor for patient survival, has not been comprehensively investigated. Here, we collected formalin-fixed paraffin-embedded tumor tissue and matched normal samples of 32 PSCC patients, including 14 LNM patients and 18 clinically node-negative patients, to implement a whole-exome sequencing. Comparison of genomic features among different lymph node status subgroups was conducted after genomic profiling and its effects on patient survival were explored. Top-ranked recurrent gene mutants in our PSCC cohort were TP53 (13/32), NOTCH1 (12/32), CDKN2A (11/32), TTN (9/32) and FAT1 (8/32), mainly identified in the Notch, Hippo, cell cycle, TP53, RTK-RAS and PI3K pathways. While CDKN2A was confirmed to be the driver gene in all PSCC patients, certain gene mutants were significantly enriched in LNM involved patients, including TP53 (9/14 vs. 4/18, p = 0.029) and GBF1 (4/14 vs. 0/18, p = 0.028). Overall survival stratification of PSCC patients were found to be significantly correlated with mutations of three genes, including PIK3CA (Hazard ratio [HR] = 4.15, p = 0.029), CHD7 (HR = 4.82, p = 0.032) and LAMC3 (HR = 15.9, p < 0.001). PIK3CA and LAMC3 held a higher prevalence in patients with LNM compared to those without LNM (PIK3CA: 3/14 vs. 1/18, LAMC3: 2/14 vs. 1/18). Our finding demonstrated that genomic divergence exists across PSCC patients with different lymph node statuses, and it may be correlated with their survival outcome. It helps delineate somatic evolution during tumor progression and perfect potential therapeutic intervention in this disease.

Feature selection is of particular importance in the field of drug discovery. Many methods have been put forward for feature selection during recent decades. Among them, evolutionary computation has gained increasing attention owing to its superior global search ability. However, there still lacks a simple and efficient software for drug developers to take advantage of evolutionary computation for feature selection. To remedy this issue, in this paper, a user-friendly and standalone software, named ECoFFeS, is developed. ECoFFeS is expected to lower the entry barrier for drug developers to deal with feature selection problems at hand by using evolutionary algorithms. To the best of our knowledge, it is the first software integrating a set of evolutionary algorithms (including two modified evolutionary algorithms proposed by the authors) with various evaluation combinations for feature selection. Specifically, ECoFFeS considers both single-objective and multi-objective evolutionary algorithms, and both regressionand classification-based models to meet different requirements. Five data sets in drug discovery are collected in ECoFFeS. In addition, to reduce the total analysis time, the parallel execution technique is incorporated into ECoFFeS. The source code of ECoFFeS can be available from https://github.com/JiaweiHuang/ECoFFeS/.

BACKGROUND: The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial. METHODOLOGY/PRINCIPAL FINDINGS: The purpose of this study is to evaluate the role of CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly genotypes in colorectal cancer susceptibility. We performed a meta-analysis on all the eligible studies that provided 5,817 cases and 6,544 controls for CYP1A2*F (from 13 studies), 9219 cases and 10406 controls for CYP1B1 Leu432Val (from 12 studies), 6840 cases and 7761 controls for CYP1B1 Asn453Ser (from 8 studies), and 4302 cases and 4791 controls for CYP1B1Arg48Gly (from 6 studies). Overall, no significant association was found between CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly and colorectal cancer risk when all the eligible studies were pooled into the meta-analysis. And in the subgroup by ethnicity and source of controls, no evidence of significant association was observed in any subgroup analysis. CONCLUSIONS/SIGNIFICANCE: In summary, this meta-analysis indicates that CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly polymorphisms do not support an association with colorectal cancer, and further studies are needed to investigate the association. In addition, our work also points out the importance of new studies for CYP1A2*F polymorphism in Asians, because high heterogeneity was found (dominant model: I(2) = 81.3%; heterozygote model: I(2) = 79.0).

Direct or ex vivo BMP9 adenoviral gene therapy can induce massive bone formation at the injection sites and clearly promote spinal fusion. A comprehensive analysis of the osteogenic activity indicated that BMP9 was one of the most potent inducers of osteogenic differentiation both in vitro and in vivo among 14 types of human BMPs. However, genetic variations and whether they correlated with OPLL were not considered. We have sequenced the complete BMP9 gene in 450 patients with OPLL and in 550 matched controls. Analyses were performed on single markers and haplotypes. Single marker tests identified 6 SNPs, among which the minor alleles of rs7923671 (T>C; P=0.0026; OR: 1.33, CI: 1.10-1.60), rs75024165 (C>T, Thr304Met; PC; P

Background: The association of platelet reactivity and clinical outcomes, especially stent thrombosis, was not so clear. We sought to investigate whether high platelet reactivity affects clinical outcomes of patients with drug eluting stents (DESs) implantation. Methods: All enrolled individuals treated with DESs implantation were evaluated by PL-11, using sequentially platelet counting method. The primary end point was the occurrence of definite and probable stent thrombosis at 2 years. The secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all cause death, spontaneous myocardial infarction (MI), target vessel revascularization (TVR), and ischemic stroke. Results: A total of 1331consecutive patients were enrolled at our center. There were 91 patients (6.8 %) identified with high platelet reactivity (HPR) on aspirin, and 437 patients (32.9 %) with HPR on clopidogrel. At 2-year followup, the incidence of stent thrombosis was significantly higher in patients with HPR on aspirin (9.9 % vs. 0.4 %, p < 0. 001), and HPR on clopidogrel (3.0 % vs. 0.1 %, p < 0.001). There were increased MACCE in the HPR on aspirin group (16.5 % vs. 8.5 %, p = 0.021), mainly driven by the higher all cause death (7.7 % vs. 1.6 %, p = 0.002) and MI (9.9 % vs. 1.9 %, p < 0.001) in the HPR on aspirin group. Similarly, the rate of MACCE was higher in the HPR on clopidogrel group (12.4 % vs. 7.4 %, p = 0.004). No differences in all bleeding and hemorrhagic stroke were observed. Conclusions: The present study demonstrated that high platelet reactivity on both aspirin and clopidogrel were associated with incremental stent thrombosis following DESs implantation. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported a discrepancy in baseline characteristics and outcomes after percutaneous coronary intervention between men and women. However, this finding has never been verified in the Chinese population. The present study analyzed two-year clinical outcomes after placement of coronary drug-eluting stents in Chinese men and women. Methods: From January 2005 to December 2010, a total of 3804 Chinese patients (2776 men, 1028 women) who underwent drug-eluting stent implantation were studied prospectively. The primary endpoint was the composite major adverse cardiac event (MACE) rate, including myocardial infarction, cardiac death, and target vessel revascularization at two years. Stent thrombosis served as the safety endpoint. Propensity score matching was used to compare the adjusted MACE rate between the two groups. Results: At two-year follow-up, unadjusted rates of myocardial infarction, non-ST segment elevation myocardial infarction, target vessel revascularization, and MACE were significantly different between men (6.84%, 4.6%, 13.1%, and 21.7%, respectively) and women (3.8% [P = 0.001], 2.0% [P < 0.001] 10.3% [P = 0.025], and 16.3% [P<0.001], respectively). After propensity score matching, there were no significant differences in composite MACE and individual endpoints at two years between the genders. Conclusion: Despite all the unfavorable risk factor clustering in women and complex coronary disease in men, the two-year clinical outcomes after coronary stent placement were comparable between Chinese women and men. [ABSTRACT FROM AUTHOR]

Background: Stent grafting for treatment of type B aortic dissection has been extensively used. However, the difference in the long-term clinical outcome between patients with chronic versus acute type B aortic dissection remains unknown. This study aimed to analyze the difference in long-term clinical outcome after endovascular repair for patients with chronic ($2 weeks) versus acute (,2 weeks) type B aortic dissection. Methods: Between May 2000 and June 2011, a total of 174 patients with type B aortic dissection (56 chronic, 118 acute) treated by endovascular repair were studied prospectively. Follow-up three-dimensional computed tomography scanning and aortoangiography were scheduled at 3-6 months after the index procedure. Propensity score matching was used to compare the difference in the endpoint between the two groups. Results: The procedure-related event rate was 18.6% in the acute group and 5.4% in the chronic group (P = 0.021), but this difference became nonsignificant after propensity score matching. At the end of follow-up (mean 2.49 years), overall and aorta-related mortality was 11.0% and 7.6%, respectively, in the acute group, and was not significantly different from that in the chronic group (3.6% and 3.6%, P = 0.148 and P = 0.506, respectively). Both false and true lumina showed significant remodeling over time, with .93% complete false-lumen thrombosis. Untreated tear and type I endoleak were predictors of clinical events during follow-up. Conclusion: Comparable long-term clinical results were achieved in patients with chronic or acute type B aortic dissection after implantation of a stent graft. [ABSTRACT FROM AUTHOR]

Background: While many studies confirmed the importance of fractional flow reserve (FFR) in guiding complex percutaneous coronary interventions (PCI), data regarding the significance of FFR for bifurcation lesions are still lacking. Methods: Between October 2008 and October 2009, 51 patients with true bifurcation lesions were consecutively enrolled and randomized into double kissing (DK) crush (n = 25), and provisional 1-stent (n = 26) groups. FFR measurements at baseline and hyperemia were measured at pre-PCI, post-PCI, and at 8-month follow-up. Results: Clinical follow-ups were available in 100% of patients while only 33% of patients underwent angiographic follow-up. Baseline clinical and angiographic characteristics were matched between the 2 groups. Pre-PCI FFR of the main branch (MB) in the DK group was 0.76 ± 0.15, which was significantly lower than in the provisional 1-stent group (0.83 ± 0.10, P = 0.029). This difference disappeared after the PCI procedure (0.92 ± 0.04 vs. 0.92 ± 0.05, P = 0.58). There were no significant differences in terms of baseline, angiographic, procedural indexes, and FFR of side branch (SB) between the 2 treatment arms. However, immediately after PCI, the patient with DK crush had higher FFR in the SB as compared to the provisional 1-stent group (0.94 ± 0.03 vs. 0.90 ± 0.08, P = 0.028, respectively) and also they had lower diameter stenosis (8.59 ± 6.41% vs. 15.62 ± 11.69%, P = 0.015, respectively). Conclusion: In the acute phase, immediately after PCI for bifurcation lesion, DK crush stenting was associated with higher FFR and lower residual diameter stenosis in the SB, as compared with the provisional 1-stent group. (J Interven Cardiol 2010;23:341–345) [ABSTRACT FROM AUTHOR]

Background: Endothelial shear stress is one of the local hemodynamic factors suspected in the development of coronary atherosclerosis in bifurcation lesions. In patients with provisional stenting, the endothelial shear stress (SS) distribution is unknown. Objective: The aim of this study was to investigate the magnitude and distribution of the SS of coronary bifurcation lesions stenting by the provisional approach. Methods: Ten consecutive patients were included in this study. Quantitative coronary analysis, flow study, and three-dimensional computational analysis with the aid of the commercial software CD STAR-CCM+ were done before and after the provisional stenting procedure and also 8 months later. Results: Clinical and angiographic follow-up were available in all patients. No patient had a side branch (SB) stent. At the 8-month follow-up, no major adverse cardiac event (MACE) occurred. There was also no clinical and angiographic restenosis. Before PCI, the distal main vessel (MV)-lateral, and the SB-lateral subsegments had relative nonsignificant lower SS value (4.08 ± 2.78 Pa and 4.35 ± 5.04 Pa, respectively) when compared to other segments. After 8-month follow-up, sustained decreased SS value was shown in the distal MV-lateral segment (4.08 ± 2.78–1.68 ± 1.65 Pa), when compared with significantly increased SS value in the SB-lateral subsegment 4.35 ± 5.04–16.50 ± 40.45 Pa). The explanation is that after stenting in the MV, the flow was redistributed immediately after percutaneous coronary intervention (PCI) and reversed back to its original 8 months later. However, the growth of the fibrous tissue causing in-stent restenosis (ISR) is prohibited by sirolimus on the stent struts. In contrast, in a branch opened up by plain old balloon angioplasty (POBA), the flow did not change much, the flow could even be worse because it is shifted to the MV after the cross-sectional area of the MV improved by stenting . However, thanks to POBA, there is increased fibrous tissue formation, enough to increase the SS and prevent further accumulation of cell and cholesterol needed for more restenosis. Conclusion: In the provisional approach, low endothelial SS correlated with no restenosis for patients who underwent stenting of the MV, while a contradictory combination of high SS and no restenosis was seen in the SB after only POBA. The mechanism of prevention of restenosis in the SB is by increasing the SS while in the MV, the mechanism of prevention of ISR is secondary to sirolimus on the stents struts. (J Interven Cardiol 2010;23:319–329) [ABSTRACT FROM AUTHOR]

Background: Wall shear stress (SS) plays an important role in the initiation and proliferation of coronary atherosclerosis, especially for bifurcations. Stenting in the coronary artery will cause many different changes in velocity, flow, cross-sectional area, and especially the wall SS. However, it is still unknown how much wall SS distribution varies with stenting in coronary bifurcation. Objective: The purpose of this study was to investigate the magnitude and distribution of wall SS after the classical crush stenting for bifurcation lesions. Methods: Eleven patients with true coronary bifurcation stenting by the classical crush technique were included. We studied the difference of wall SS between restenosis and nonrestenosis groups in these patients. The differences in SS between preprocedure and postprocedure, as well as between immediately postprocedure and after an 8-month follow-up, were also analyzed. Diameter stenosis or minimal lumen diameter were measured by quantitative coronary analysis. The commercial CD STAR-CCM+ was used to calculate the SS. Results: At baseline, the SS in all the segments of all patients was high. The baseline SS of the restenosis group was 50% lower than the nonrestenosis group. Immediately after percutaneous coronary intervention (PCI), the SS in both areas decreased; however, the SS of the nonrestenosis group decreased to its lowest level possible while the SS of the restenosis group decreased moderately. Eight months later, the SS of all the segments of the nonrestenosis group remained persistently low at the same level of right after PCI. In contrary, the SS in the restenosis group returned to near its baseline level. Conclusion: From our study, after a 2-stent crush technique using drug-eluting stents (DES), the degree of SS reduction appears to predict in-stent restenosis (ISR). A SS decrease to its lowest level and remaining homogenously low is a prime condition to prevent ISR. A baseline low SS, which decreases minimally after PCI and recovers to around its baseline level, appears to be the setting for restenosis. These conditions can be evaluated as predictors of lesions that may need surveillance angiography and proper IVUS evaluation to prevent future in-stent restenosis. (J Interven Cardiol 2010;23:330–340) [ABSTRACT FROM AUTHOR]

Objectives: We investigated the clinical outcome of stenting of unprotected left main coronary artery (LMCA). Methods: We studied 164 patients with nonbifurcated LMCA lesions (group A) and 96 patients with distal bifurcated lesions (group B). Results: Clinical follow-up was available in 100%. Angiographic follow-up was 87.3% in group A and 86% in group B (p = 0.922). There were significant differences in major adverse cardiac events at 1 (p = 0.014) and 2 years (p = 0.002) between group B (19.8%, 25.0%) and group A (9.1%, 10.4%), mainly due to increased target-vessel revascularization (16.7, 21.9% in group B vs. 6.1, 7.3% in group A, p = 0.006 and 0.001, respectively). The double-stent technique was associated with worse outcomes at 1 year in group B compared to group A. Bifurcation lesions (HR 3.42, 95% CI 1.34–5.61, p = 0.001), diabetes (HR 2.68, 95% CI 2.01–12.11, p = 0.015), three-vessel disease (HR 0.83, 95% CI 0.27–0.96, p = 0.001), incomplete revascularization (HR 0.15, 95% CI 0.11–0.35, p = 0.001) and stent diameter (HR 5.05, 95% CI 2.71–10.01, p = 0.03) were the independent factors of major adverse cardiac events in the whole patient cohort. Conclusion: Stenting unprotected distal bifurcated LMCA was associated with unfavorable results when compared to stenting other LMCA lesions. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]