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Background: Intra-abdominal infection after curative surgery for colorectal cancer is a serious complication associated with an increased risk of recurrence. Lipopolysaccharides (LPS)—an essential component of the cell wall of Gram-negative bacteria—were found to exert a protumorigenic effect by stimulating the inflammatory pathology and formation of neutrophil extracellular traps (NETs). This study was conducted to test whether LPS-induced formation of NETs promotes the development of cancer and metastasis. Methods: The clinical characteristics, incidence of relapse, and serum myeloperoxidase–DNA complexes of 40 patients with infection and 40 patients without infection after curative surgery were analyzed. The effects of LPS on the induction of NETs were evaluated in a mouse model of colorectal cancer and liver metastasis. The toll-like receptor 9 (TLR9)—a DNA receptor—was knocked down to assess its effect on the mitogen-activated protein kinase pathway and activities implicated in the formation of NETs. Results: Analysis of the clinical data obtained from these patients showed the significant relation of the formation of NETs and incidence of metastasis and survival rates. Subsequent in vitro experiments revealed an increased level of citrullinated-histone H3 and myeloperoxidase–DNA in LPS-injected mice with colorectal cancer. In the mimic metastatic model, injection of LPS enhanced the metastatic capacity, which was then attenuated by DNase I. This suggested that the formation of NETs was activated by LPS. Injection of TLR9-knockdown HCT116 cells in mice, followed by induction through LPS, mitigated the level of citrullinated-histone H3 and myeloperoxidase–DNA. This finding implied that the formation of NETs was suppressed. Conclusion: These findings shed light on the mechanism underlying the relationship between the elevated rate of colorectal cancer recurrence in patients who underwent surgery and the incidence of infection. This mechanism involves the protumorigenic activities of LPS-induced formation of NETs. The NETs which could be mediated by the TLR9 and the mitogen-activated protein kinase signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: Emerging evidence has shown that interleukin (IL)-17A is implicated in the pathogenesis of allergic rhinitis (AR). Thymic stromal lymphopoietin (TSLP) orchestrates the immune response toward a Th2 phenotype. Although increased TSLP is found in AR, the contribution of IL-17A in TSLP production by nasal fibroblasts is not well understood. We aimed to investigate the effect and mechanism of IL-17A on TSLP production by human nasal fibroblasts (HNFs) from AR patients. Methods: HNFs from AR patients were cultured and stimulated with IL-17A in the absence or presence of a Janus kinase (JAK) 2 or JAK1/3 inhibitor. Western blotting was used to assay phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and nuclear factor-kappa B (NF-κB) p65 in HNFs. The TSLP expression in the cells and culture supernatants was evaluated by real-time polymerase chain reaction and enzyme-linked immunoassay. Results: Stimulation with IL-17A induced STAT3 phosphorylation, which was inhibited by the pretreatment with JAK2 inhibitor AZD1480 or JAK1/3 inhibitor tofacitinib. IL-17A promoted the nuclear translocation of NF-κBp65 protein, leading to increased TSLP production, while the pre-incubation with AZD1480 prior to IL-17A attenuated these effects. However, the pre-incubation with tofacitinib before IL-17A stimulation had no impact on the expression of NF-κBp65 and TSLP. Conclusions: IL-17A up-regulated TSLP production by HNFs through JAK2/NF-κB pathway. Although IL-17A induced STAT3 activation through JAK1/2/3, IL-17A-mediated TSLP expression was not dependent on STAT3 signaling. These observations would provide mechanistic insight into therapeutic strategies to improve the immune and inflammation associated with Th17A in the management of AR. [ABSTRACT FROM AUTHOR]

Purpose: Epithelial thymic stromal lymphopoietin (TSLP) promotes Th2 inflammatory responses through induction of OX40 ligand (OX40L) on dendritic cells in allergic rhinitis (AR). Emerging evidence supports the important role of histamine H4 receptor (H4R) in allergic inflammation. This study aimed to investigate the effects of H4R in Th2-cytokine profile mediated by TSLP in AR. Methods: Human nasal epithelial cells (HNECs) from AR patients were stimulated with histamine in the presence or absence of H4R agonist (4-methylhistamine, 4-MH) and antagonist (NJ7777120, JNJ) or H1R agonist (2-pyridylethylamine). TSLP protein was measured by Western blotting and ELISA. To further elucidate the role of H4R in the in vivo situation of experimental AR, rats were sensitized and treated with JNJ or 4-MH. TSLP and OX40 ligand (OX40L) in the nasal mucosa were assayed by Western blotting. Th2 cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were detected by ELISA. Results: Histamine alone did not induce TSLP production by HNECs. The pre-incubation with 4-MH prior to histamine promoted TSLP expression, which was inhibited by the stimulation with JNJ prior to histamine and 4-MH. The pre-incubation with 2-pyridylethylamine before histamine stimulation had no impact on TSLP production. In AR rats, the levels of TSLP and OX40L protein were increased as well as Th2 cytokines, which was further up-regulated by 4-MH treatment, while JNJ treatment attenuated these effects. Conclusions: H4R activation induced TSLP production by HNECs, which up-regulated OX40L expression in the nasal mucosa of sensitized rats. These factors promoted Th2-cytokine profile in AR. [ABSTRACT FROM AUTHOR]

In order to solve the problem of wrinkling in traditional multi-point forming (MPF), a new multi-point forming process, namely multi-point forming with individually controlled force-displacement (MPF-ICFD), was proposed. The core idea of this process is to impose a full-area normal constraint on the sheet metal during the whole forming process. Therefore, the deformation sequence of the sheet metal is changed from the local constraint and the whole deformation in the traditional MPF to the whole constraint and the local deformation so as to completely eliminate the noncontact region and avoid wrinkling. In this paper, the saddle surface part was taken as the research object. The influence of normal restraint on critical wrinkle stress is studied by mechanical analysis, and the wrinkle restraint mechanism under normal restraint is revealed. The deformation behavior of saddle surface parts was studied by forming experiments, and the wrinkling law of saddle surface parts under different constraints is obtained. The deformation characteristics of saddle surface parts were analyzed by numerical simulation, and the critical stress distribution rules of the sheet metal were given. It is shown that the critical wrinkling stress of the sheet metal is significantly increased in MPF-ICFD compared with that in traditional MPF, and the increased value is proportional to the magnitude of normal constrained force. Besides, the wrinkling phenomenon of saddle surface parts is significantly suppressed, and the surface quality of workpiece is obviously improved. In addition, the stress state change from compressive stress to tensile stress in the core region of the sheet metal was prone to wrinkle. [ABSTRACT FROM AUTHOR]

This systematic review applied meta-analytic procedures to evaluate the curative effect of trans-septal suturing versus nasal packing after septoplasty. Computerized search of the published literature in PubMed, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, WANFANG, CNKI databases. Randomized trials investigating trans-septal suturing versus nasal packing following septoplasty in patients with deviated nasal septum. Adhesion, septal hematoma, bleeding, septal perforation, infection, pain, headache, or residual septal deviation per randomized patients. 19 randomized controlled trials of 1845 subjects were included. Meta-analysis showed that postoperative pain, headache, and adhesion were significantly lower in trans-septal suturing group. Nasal packing and trans-septal suturing technique appear to be equivalent with regard to postoperative bleeding, hematoma, septal perforation, infection, and residual septal deviation. Trans-septal suturing technology is not only associated with less patient pain, headache, and lower occurrence rate of adhesion after septoplasty but it also relates to higher patient satisfaction and an improved quality of life. The suturing technology can be used as a substitute for traditional nasal packing of the first-line treatment. More well-designed studies are needed to confirm the effect of trans-septal suturing following septoplasty. [ABSTRACT FROM AUTHOR]

The purpose of the present work is to study the buckling problem with plate/shell topology optimization of orthotropic material. A model of buckling topology optimization is established based on the independent, continuous, and mapping method, which considers structural mass as objective and buckling critical loads as constraints. Firstly, composite exponential function (CEF) and power function (PF) as filter functions are introduced to recognize the element mass, the element stiffness matrix, and the element geometric stiffness matrix. The filter functions of the orthotropic material stiffness are deduced. Then these filter functions are put into buckling topology optimization of a differential equation to analyze the design sensitivity. Furthermore, the buckling constraints are approximately expressed as explicit functions with respect to the design variables based on the first-order Taylor expansion. The objective function is standardized based on the second-order Taylor expansion. Therefore, the optimization model is translated into a quadratic program. Finally, the dual sequence quadratic programming (DSQP) algorithm and the global convergence method of moving asymptotes algorithm with two different filter functions (CEF and PF) are applied to solve the optimal model. Three numerical results show that DSQP&CEF has the best performance in the view of structural mass and discretion. [ABSTRACT FROM AUTHOR]

In this paper, a new process of multi-point forming with individually controlled force-displacement (MPF-ICFD) is presented to reduce the springback in the traditional multi-point forming (MPF). An experimental setup was designed and manufactured, and the contrast experiment was conducted to investigate the differences between the traditional MPF and the proposed MPF-ICFD. Furthermore, the stress state and springback mechanism in both processes were analyzed with the plastic forming theory. The differences in springback were also investigated with 1060 aluminum alloy and Q 295 steel. The results showed that the specimens in MPF-ICFD presented an excellent deformation uniformity and are consistent with the target profile. The springback magnitude of 1060 aluminum alloy is 34.63% in MPF while 7.51% in MPF-ICFD, and the springback magnitude of Q 295 steel is 31.16% in MPF while 17.02% in MPF-ICFD. The results demonstrate that the springback can be strongly inhibited by MPF-ICFD. [ABSTRACT FROM AUTHOR]

In this paper, a model of topology optimization with linear buckling constraints is established based on an independent and continuous mapping method to minimize the plate/shell structure weight. A composite exponential function (CEF) is selected as filtering functions for element weight, the element stiffness matrix and the element geometric stiffness matrix, which recognize the design variables, and to implement the changing process of design variables from 'discrete' to 'continuous' and back to 'discrete'. The buckling constraints are approximated as explicit formulations based on the Taylor expansion and the filtering function. The optimization model is transformed to dual programming and solved by the dual sequence quadratic programming algorithm. Finally, three numerical examples with power function and CEF as filter function are analyzed and discussed to demonstrate the feasibility and efficiency of the proposed method. [ABSTRACT FROM AUTHOR]

To solve the problem of springback in traditional multi-point forming (MPF), a new multi-point forming process, namely, multi-point forming with individually controlled force–displacement (MPF-ICFD), is proposed. In this manuscript, traditional MPF and MPF-ICFD are compared. Taking the cylindrical surface as the research object, the change in the springback of a plate is analysed by experiments, and the distribution of the strain and wall thickness of the plate is analysed by numerical simulation. Theoretical analysis is used to calculate the forming window for the MPF-ICFD process, and the results from theoretical analysis are verified by experiments and numerical simulation. The results show that the springback of 1060 aluminium alloy and Q295 for MPF-ICFD can be decreased by 73.8% and 45.5%, respectively, compared with traditional MPF. In traditional MPF, the strain uniformity of the plate is poor, and the maximum thinning rate is 4.5%. For MPF-ICFD, the strain is relatively uniform, and the maximum thinning rate is 0.25%. For an aluminium alloy sheet with a wall thickness of 1.5–3 mm, the upper and lower limits of the forming force for a single head are observed to change linearly from 6.3 to 12.6 kN and from 0.5 to 1 kN, respectively. [ABSTRACT FROM AUTHOR]

A new topology optimization method is formulated for lightweight design of multimaterial structures, using the independent continuous mapping (ICM) method to minimize the weight with a prescribed nodal displacement constraint. Two types of independent topological variable are used to identify the presence of elements and select the material for each phase, to realize the interpolations of the element stiffness matrix and total weight. Furthermore, an explicit expression for the optimized formulation is derived, using approximations of the displacement and weight given by first- and second-order Taylor expansions. The optimization problem is thereby transformed into a standard quadratic programming problem that can be solved using a sequential quadratic programming approach. The feasibility and effectiveness of the proposed multimaterial topology optimization method are demonstrated by determining the best load transfer path for four numerical examples. The results reveal that the topologically optimized configuration of the multimaterial structure varies with the material properties, load conditions, and constraint. Firstly, the weight of the optimized multimaterial structure is found to be lower than that composed of a single material. Secondly, under the precondition of a displacement constraint, the weight of the topologically optimized multimaterial structure decreases as the displacement constraint value is increased. Finally, the topologically optimized multimaterial structures differ depending on the elastic modulus of the materials. Besides, the established optimization formulation is more reliable and suitable for use in practical engineering applications with structural performance parameters as constraint. [ABSTRACT FROM AUTHOR]

Aims: Variation in tree litter inputs and understory vegetation caused by human disturbances and climate change in forest plantations can extend to alter forest stability and productivity over time. Here, we explore how tree litter inputs interact with understory plant management to influence belowground processes in a managed forest plantation. Methods: We conducted a two-factor nested experimental manipulation of pine litter and understory vegetation in a nutrient-poor Pinus sylvestris var. mongolica plantation. Three levels of tree litter manipulation (ambient litter, litter removal and litter addition) were nested in two levels of understory manipulation (understory intact and understory removal). After two years of manipulation, mineral soils were analyzed for total and extractable C, N and P concentrations, N mineralization, enzyme activities, as well as the microbial community structure (as indicated by phospholipid fatty acids). Results: Litter removal had little impact on C and nutrient cycling as well as microbial biomass and community structure in this low nutrient pine plantation; however, litter addition and the removal of the understory vegetation had large impacts on these processes. Litter addition elevated soil microbial biomass, acid phosphatase and β-1, 4-glucosidase activities, by a much greater degree when the understory vegetation was intact than when the understory was removed. Litter addition also reduced soil available P by 39% when the understory vegetation was intact, and reduced soil available P by 74% and NO -N by 45% when the understory was removed. Litter addition significantly reduced the ratio of Gram-positive to Gram-negative bacteria as well as the ratio between PLFA markers cy17:0 and 16:1ω7. Understory removal reduced the ratio of PLFA markers cy17:0 to 16:1ω7. Conclusions: Our study results show that, in this managed pine plantation, soil microbial community structure and function were more sensitive to an increase rather than to a decrease in pine litter inputs. Further, we found that the presence of understory vegetation can increase soil microbial biomass and alleviate the reduction in available N and P concentrations induced by pine litter addition. Thus, preservation of the understory vegetation is an effective way to maintain the functional stability of managed forests on nutrient-poor soils. [ABSTRACT FROM AUTHOR]

Current therapeutic options for acute kidney injury (AKI) are limited to the use of supportive measures and dialysis. A recent approach that has sparked great interest and gained enormous popularity is the implantation of stem cells to repair acutely damaged kidney organ. Hypoxia inducible factor-1α (HIF-1α) is effective in protecting the kidney from ischemia and nephrotoxicity. In this study, we investigated whether HIF-1α-modified adipose-derived stem cells (ASCs) had an enhanced protective effect on cisplatin-induced kidney injury in vivo. Cisplatin-induced AKI was established in nude mice. Our study demonstrated that HIF-1α-modified ASCs obviously promoted the recovery of renal function, ameliorated the extent of histologic injury and reduced renal apoptosis and inflammation, but HIF-1α-modified ASCs homed to kidney tissues at very low levels after transplantation. In addition, we also found that HIF-1α-modified ASCs significantly increased HO-1 expression in cisplatin-induced AKI in vivo. Thus, our study indicated HIF-1α-modified ASCs implantation could provide advanced benefits in the protection again AKI, which will contribute to developing a new therapeutic strategy for the treatment of AKI. [ABSTRACT FROM AUTHOR]

Purpose: Appropriate prescription of oral anticoagulants (OACs) and good patient adherence are essential to ensure optimal anticoagulation in patients with atrial fibrillation (AF). The aim of this study is to develop a mobile health tool to aid both clinicians and patients with AF in anticoagulation therapy. Methods: In this study, a novel anticoagulation management model integrating decision support and patient follow-up, the I-Anticoagulation, was developed based on a WeChat Mini Program. With this tool, the risks of stroke and bleeding in AF patients can automatically be calculated according to their characteristics. Anticoagulation regimens were recommended based on a trade-off analysis that balances stroke and bleeding risks according to recent clinical guidelines. A shared decision can be made with full communication between medical professionals and patients. Moreover, follow-up was also conducted using I-Anticoagulation. Results: A total of 120 AF patients receiving anticoagulants (40 received warfarin and 80 received non-vitamin K antagonist oral anticoagulants [NOACs]) were included in the pilot study. The incidence of thromboembolic events was 2.5% and 1.3%, and the rates of bleeding events were 22.5% and 13.8% in the warfarin and NOAC groups, respectively. Generally, self-reported adherence was high, and the satisfaction with anticoagulation was good in all patients with AF. Conclusion: Overall, the anticoagulation management model developed in this study could be involved in the full process of anticoagulation therapy in AF patients to improve rationality, adherence, and satisfaction in both medical professionals and patients. However, the usability, feasibility, and acceptability of the I-Anticoagulant-based anticoagulation management model need to be further assessed through well-designed random clinical trials. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the growth and fixed points of solutions of higher-order linear differential equations in the unit disc. We extend the coefficient conditions to a type of one-constant-control coefficient comparison and obtain the same estimates of iterated order of solutions. We also obtain better estimates by providing a precise value of iterated order of solution instead of a range of that in the case of coefficient characteristic function comparison. Moreover, we utilize iteration to investigate and estimate the fixed points of solutions' arbitrary-order derivatives with higher-order equations f (k) + A k − 1 (z) f (k − 1) + ⋯ + A 1 (z) f ′ + A 0 (z) f = 0 and provide a concise method to judge if the items generated by the iteration do not vanish identically and ensure the iteration proceeds. Our results are an improvement over those by B. Belaïdi, T. B. Cao, G. W. Zhang and A. Chen. [ABSTRACT FROM AUTHOR]

Pediatric low-grade gliomas (PLGGs) consist of a number of entities with overlapping histological features. PLGGs have much better prognosis than the adult counterparts, but a significant proportion of PLGGs suffers from tumor progression and recurrence. It has been shown that pediatric and adult low-grade gliomas are molecularly distinct. Yet the clinical significance of some of newer biomarkers discovered by genomic studies has not been fully investigated. In this study, we evaluated in a large cohort of 289 PLGGs a list of biomarkers and examined their clinical relevance. TERT promoter (TERTp), H3F3A and BRAF V600E mutations were detected by direct sequencing. ATRX nuclear loss was examined by immunohistochemistry. CDKN2A deletion, KIAA1549-BRAF fusion, and MYB amplification were determined by fluorescence in situ hybridization (FISH). TERTp, H3F3A, and BRAF V600E mutations were identified in 2.5, 6.4, and 7.4% of PLGGs, respectively. ATRX loss was found in 4.9% of PLGGs. CDKN2A deletion, KIAA1549-BRAF fusion and MYB amplification were detected in 8.8, 32.0 and 10.6% of PLGGs, respectively. Survival analysis revealed that TERTp mutation, H3F3A mutation, and ATRX loss were significantly associated with poor PFS (p < 0.0001, p < 0.0001, and p = 0.0002) and OS (p < 0.0001, p < 0.0001, and p < 0.0001). BRAF V600E was associated with shorter PFS (p = 0.011) and OS (p = 0.032) in a subset of PLGGs. KIAA1549-BRAF fusion was a good prognostic marker for longer PFS (p = 0.0017) and OS (p = 0.0029). MYB amplification was also a favorable marker for a longer PFS (p = 0.040). Importantly, we showed that these molecular biomarkers can be used to stratify PLGGs into low- (KIAA1549-BRAF fusion or MYB amplification), intermediate-I (BRAF V600E and/or CDKN2A deletion), intermediate-II (no biomarker), and high-risk (TERTp or H3F3A mutation or ATRX loss) groups with distinct PFS (p < 0.0001) and OS (p < 0.0001). This scheme should aid in clinical decision-making. [ABSTRACT FROM AUTHOR]

Inflammation and immunoreaction markers were correlated with the survival of patients in many tumors. However, there were no reports investigating the relationships between preoperative hematological markers and the prognosis of medulloblastoma (MB) patients based on the molecular subgroups (WNT, SHH, Group 3, and Group 4). A total 144 MB patients were enrolled in the study. The differences of preoperative hematological markers among molecular subgroups of MB were compared by One-way ANOVA method. Kaplan-Meier method was used to calculate the curves of progression free survival (PFS) and overall survival (OS). The comparison of survival rates in different groups were conducted by the Log-rank test. Multivariate analysis was used to evaluate independent prognostic factors. Increased preoperative NLR (neutrophil-to-lymphocyte ratio, PFS, P = 0.004, OS, P < 0.001) and PLR (platelet-to-lymphocyte ratio, PFS, P = 0.028, OS, P = 0.003) predicted poor prognosis in patients with MB, while preoperative MLR (monocyte-to-lymphocyte ratio), MPV (mean platelet volume), PDW (platelet distribution width), and AGR (albumin-to-globulin ratio) were revealed no predictive value on the prognosis of patients with MB. Furthermore, high preoperative NLR and PLR predicted unfavorable prognosis in childhood MB patients. However, preoperative NLR and PLR were not associated with the prognosis in adult MB patients. Multivariate analysis demonstrated preoperative NLR (PFS, P = 0.029, OS, P = 0.005) and PLR (PFS, P = 0.023, OS, P = 0.005) were the independent prognostic factors in MB patients. Emphatically, the levels of preoperative NLR and PLR in Group 3 MB were significantly higher than those in WNT MB. High preoperative NLR was associated with unfavorable OS in Group 3 (P = 0.032) and Group 4 (P = 0.027) tumors. Similarly, increased preoperative PLR predicted poor PFS (P = 0.012) and OS (P = 0.009) in Group 4 tumors. Preoperative NLR and PLR were the potential prognostic markers for MB patients. Preoperative NLR and PLR were significantly associated with the survival of Group 3 and Group 4 tumors. [ABSTRACT FROM AUTHOR]