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Data are scarce regarding retrograde type A dissection (RTAD) after thoracic endovascular aortic repair (TEVAR). This study aimed to investigate the clinical characteristics and surgical treatment outcomes of patients who developed RTAD after TEVAR.From January 2015 to January 2020, 25 consecutive patients (aged 52 ± 11.69 years) of RTAD after TEVAR received open surgery. All patients received total arch replacement (TAR) with the frozen elephant trunk (FET). The proximal part of the TEVAR stent was removed using a wire scissor. The distal part of the TEVAR stent in the descending aorta was preserved. Data of 50 random patients of type A aortic dissection without prior TEVAR were collected during the same period. We compared the perioperative and midterm follow-up outcomes between patients with prior TEVAR and patients without prior TEVAR.The mean cardiopulmonary bypass time, aortic cross-clamp time, and deep hypothermic circulatory arrest time were 173.7 ± 44.1, 109.5 ± 31.4, and 21.6 ± 6.8 minutes in the RTAD group, respectively. These times are similar to those of the no-RTAD group. The median interval between the initial TEVAR procedure and RTAD was 8.5 months (range, 0-72 months). New entry tears that were induced by the proximal end of the TEVAR stent were found in 23 (92%) patients of the RTAD group. There were no significant differences in major adverse events and overall survival between the two groups.TAR with the FET technique was feasible for the treatment of RTAD after TEVAR, with acceptable early and midterm results.

In the present work, we investigate the dynamic behavior of composition operators on Hilbert spaces of Dirichlet series. Especially, we characterize completely their cyclicity. Then it is shown that there are no hypercyclic composition operators, and given a certain class of operators whose adjoints are hypercyclic. All these indicate that there are indigent cyclic composition operators.

In view of the fact that a single sentiment classification model may be unstable in classification, this paper attempts to propose a joint neural network and ensemble learning sentiment analysis method. After data preprocessing such as word segmentation on the text, combined with document vectorization method for feature extraction, we then use four basic classifiers including long short-term memory network, convolutional neural network, a serial model combining convolutional neural network and long short-term memory network, and support vector machine to train model, respectively. Finally, the integration is carried out by stacking ensemble learning. The experimental results show that the integrated model significantly improves the accuracy of text sentiment analysis and it can effectively predict the sentiment polarity of the text.

BACKGROUND: Multiple mechanisms have been proposed that lead to reduced effectiveness of trastuzumab in HER2-positive gastric cancer (GC), yet resistance to trastuzumab remains a challenge in clinics. METHODS: We established trastuzumab-resistant cells and patient-derived xenografts models to measure metabolic levels and vascular density and shape. The HER2-positive GC patient samples were used to determine clinical significance. We also measured protein expression and phosphorylation modifications to determine those alterations related to resistance. In vivo studies combining inhibitor of PFKFB3 with trastuzumab corroborated the in vitro findings. RESULTS: The 6-phosphofructo-2-kinase (PFKFB3)-mediated trastuzumab resistance pathways in HER2-positive GC by activating the glycolytic pathway. We also found vessels are chaotic and destabilised in the tumour during the trastuzumab resistance process. Inhibition of PFKFB3 significantly diminished tumour proliferation and promoted vessel normalisation in the patient-derived xenograft model. Mechanistically, PFKFB3 promoted the secretion of CXCL8 into the tumour microenvironment, and phosphorylated Ser1151 of ERBB2, enhancing the transcription of CXCL8 by activating the PI3K/AKT/NFκB p65 pathway. CONCLUSIONS: Our current findings discover that PFKFB3 inhibitors might be effective tools to overcome adjuvant therapy resistance in HER2-positive GC and reshaping the microenvironment by normalising tumour vessels is a novel strategy to overcome trastuzumab resistance. [Image: see text]

Tumor microenvironment plays vital roles in shaping cancer diversity, and CD73 (ecto-5′-nucleotidase; NT5E) is an emerging immune checkpoint in modulating cancer progression via conversion of immunostimulatory ATP into immunosuppressive adenosine. However, how the CD73 is regulated and how it functions in the progression of cancer are largely unknown. Here, we showed that CD73 was overexpressed and correlated with poor prognosis of gastric cancer. CD73 links adenosinergic signaling in microenvironment switching to induction of epithelial-to-mesenchymal transition phenotype in gastric cancer during metastasis. Further pathway and gene set enrichment analysis of transcriptome data revealed the modulation role of CD73 in RICS/RhoA signaling by its extracellular function in adenosinergic pathway, which subsequently inhibited phosphorylation of LIMK/cofilin and promoted β-catenin activation. Pharmacological inhibition of CD73 adenosinergic signaling was found to induce RICS dysfunction. Dissemination and hematogenous metastasis model showed that targeting CD73 in gastric cancer could suppress experimental metastasis. To conclude, it substantiates CD73 as a target for treatment of gastric cancer metastasis and verifies RICS as an intracellular functional molecule linking CD73/adenosinergic signaling switching to RhoA/LIMK/cofilin pathway.

Objective: The study objective was to evaluate the effect of en bloc arch reconstruction with frozen elephant trunk (FET) technique for acute type A aortic dissection.Methods: 41 patients with acute Stanford type A dissection underwent en bloc arch reconstruction combined with FET implantation between April 2018 and August 2020. The mean age of the patients was 46 ± 13 years, and 9 patients were female. One patient had Marfan syndrome. Six patients had pericardial tamponade, 9 had pleural effusion, 5 had transient cerebral ischemic attack, and 3 had chronic kidney disease.Results: The hospital mortality rate was 9.8% (4 patients). 2 (4.9%) patients had stroke, 23 (56.1%) had acute kidney injury, and 5 (12.2%) had renal failure requiring hemodialysis. During follow-up, the rate of complete false lumen thrombosis was 91.6% (33/36) around the FET, 69.4% (25/36) at the diaphragmatic level, and 27.8% (10/36) at the superior mesenteric artery level. The true lumen diameter at the same three levels of the descending aorta increased significantly while the false lumen diameter reduced at the two levels: pulmonary bifurcation and the diaphragm. The 1-, 2-and 3-year actuarial survival rates were 90.2% [95% confidence interval (CI), 81.2–99.2], 84.2% (95% CI, 70.1–98.3) and 70.2% (95% CI, 42.2–98), respectively.Conclusions: In patients with acute type A dissection, en bloc arch reconstruction with FET technique appeared to be feasible and effective with early clinical follow-up results. Future studies including a large sample size and long-term follow-up are required to evaluate the efficacy.

This study aimed to analyze the early and mid-term outcomes of aortic valve replacement with bovine pericardium in the treatment of aortic valve regurgitation.From January 2015 to March 2018, 36 patients (19 men; mean ± standard deviation [SD] age, 46.70 ± 16.60 years) underwent aortic valve replacement with bovine pericardium. The bovine pericardium was intraoperatively measured and shaped using an Ozaki template, according to the shape and size of the individual patient's aortic valve leaflets. Additional procedures were performed, including ventricular septal defect repair in 5 cases, mitral valve reconstruction in 6 cases, tricuspid valve reconstruction in 6 cases, and coronary artery bypass grafting in 3 cases.There were no perioperative deaths. One elderly patient with postoperative respiratory failure recovered after symptomatic treatment. One patient with frequent ventricular tachycardia after intraoperative cardiac re-jump underwent intra-aortic balloon counterpulsation (IABP), and the IABP device was successfully removed on the second postoperative day. Within the first 6 months of follow-up, there were no death events, no reoperation events, and no additional thromboembolic events. Follow-up echocardiography was performed for 6 months, with average left ventricular ejection fraction of 62.01 ± 3.21%, mean transvalvular pressure gradient of 11.17 ± 4.90 mmHg, and mean aortic valve velocity of 1.60 ± 0.58 m/s. Compared with the preoperative transthoracic echocardiography findings, the results at the six-month follow-up were statistically significant (P < 0.05). Mild aortic valve regurgitation occurred in 2 patients (5.56%), whereas other patients had no or only minimal aortic valve regurgitation (n = 34, 94.44%). Moderate aortic valve regurgitation occurred in one patient at 9 months after the initial operation. This was found to be due to infective endocarditis, and a biological valve was finally implanted.Aortic valve replacement with bovine pericardium in the treatment of aortic valve regurgitation is feasible, and good early and mid-term results are achieved. Long-term results need to be followed up in the future.

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important cause of post-surgery morbidity and mortality. However, it is unclear whether thromboprophylaxis with the low-molecular-weight heparin (LMWH) enoxaparin after non-orthopedic surgery could balance the cost and clinical outcomes or not. The purpose of this research was to evaluate the cost-effectiveness of enoxaparin for the universal prophylaxis of VTE and associated long-term complications in patients after non-orthopedic surgery compared with no prevention in a Chinese healthcare setting. A decision model, which included both acute VTE and long-term complications, was developed to assess the economic outcomes of the two strategies for patients after non-orthopedic surgery. Quality-adjusted life years (QALYs) and direct medical costs were measured over a 5-year horizon. Incremental cost-effectiveness ratios (ICERs) were calculated. Compared with no prevention, patients under enoxaparin treatment with Caprini risk scores of 3–4, 5–6, 7–8, and ≥ 9 increased by 0.012, 0.017, 0.034, and 0.102 in QALYs, respectively. The results were either that ICERs of thromboprophylaxis with enoxaparin over no prevention were lower than the thresholds or that thromboprophylaxis with enoxaparin was dominant. For patients with a Caprini risk score ≥ 9, thromboprophylaxis with enoxaparin is dominant across the whole drug use duration range. The sensitivity analysis confirmed the results. As the first analysis evaluating the economic outcomes of enoxaparin in patients undergoing general non-orthopedic surgery, this study suggests that thromboprophylaxis with enoxaparin is highly cost-effective compared with no prevention in patients with Caprini risk score ≥ 3.

Aims: To conduct a lifetime cost-effectiveness analysis (CEA) of rasburicase compared with standard of care (SOC) for tumor lysis syndrome (TLS) in children with hematologic malignancies from the Chinese healthcare system perspective. Materials and methods: The CEA was performed using a decision tree model with a lifetime horizon. The model explores the cost-effectiveness of rasburicase vs SOC for both preventing TLS and treating established TLS among pediatric patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and non-Hodgkin's lymphoma (NHL). Both the prophylaxis-use model and treatment-use model incorporate long-term health states of the diseases: survival without TLS and death. The efficacy data of rasburicase and SOC were obtained from published literature. Drug costs, healthcare resource utilization (HRU), and adverse event (AE) management costs were obtained via a published study with clinical experts. Costs in US dollar and quality-adjusted life year (QALY) are reported, and incremental cost-effectiveness ratios (ICERs) were also calculated. Uncertainties due to parameter fluctuations in the model were assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: During TLS prevention, compared with SOC, the ICER of rasburicase treatment in China are $17,580.04/QALY, $5,783.45/QALY, and $5,391.00/QALY for pediatric patients with AML, ALL, and NHL, respectively. For the established TLS treatment, compared with SOC, the ICERs of rasburicase treatment are $2,031.18/QALY, $1,142.93/QALY, and $990.37/QALY for pediatric patients with AML, ALL, and NHL, respectively. Limitations: The clinical data for SOC are based on the published study in China, and the rasburicase prevention or treatment failure rate was either calculated based on the risk ratio or directly from the clinical study among non-Chinese pediatric patients. Another study limitation was the lack of utility data for pediatric patients with TLS and without TLS. Thus, the utility scores of pediatric cancer survivors were used as an alternative. Conclusion: Rasburicase is estimated to be a cost-effective alternative to SOC in the prevention and treatment of TLS among Chinese pediatric patients with AML, ALL, and NHL.

In an effort to upgrade and provide a unified and improved instrument control and data acquisition system for the Oak Ridge National Laboratory (ORNL) small-angle neutron scattering (SANS) instrument suite&mdash, biological small-angle neutron scattering instrument (Bio-SANS), the extended q-range small-angle neutron scattering diffractometer (EQ-SANS), the general-purpose small-angle neutron scattering diffractometer (GP-SANS)&mdash, beamline scientists and developers teamed up and worked closely together to design and develop a new system. We began with an in-depth analysis of user needs and requirements, covering all perspectives of control and data acquisition based on previous usage data and user feedback. Our design and implementation were guided by the principles from the latest user experience and design research and based on effective practices from our previous projects. In this article, we share details of our design process as well as prominent features of the new instrument control and data acquisition system. The new system provides a sophisticated Q-Range Planner to help scientists and users plan and execute instrument configurations easily and efficiently. The system also provides different user operation interfaces, such as wizard-type tool Panel Scan, a Scripting Tool based on Python Language, and Table Scan, all of which are tailored to different user needs. The new system further captures all the metadata to enable post-experiment data reduction and possibly automatic reduction and provides users with enhanced live displays and additional feedback at the run time. We hope our results will serve as a good example for developing a user-friendly instrument control and data acquisition system at large user facilities.

Aims Most therapeutic drugs of endometriosis have been contraceptives but symptoms recur in up to 75% of cases, which makes it a presses need to try to find novel and safer therapeutic drugs. Imperatorin is a furanocoumarin existing in many plants, possessing multiple activities, including anti-inflammatory. The purpose of this study was to assess the effects and mechanisms of imperatorin in endometriosis. Main methods Ectopic endometrial volume and hematoxylin-eosin staining were used to estimate the effects of imperatorin in experimental endometriosis model rats. Potential mechanisms of imperatorin in endometriosis were systematically analyzed by network pharmacology and molecular docking. Western blotting and enzyme-linked immunosorbent assay were employed to evaluate proteins expression and cytokines levels in PI3K/Akt/NF-κB pathway. Key findings Imperatorin could significantly inhibit the growth and ameliorate the histopathological features of ectopic endometrium in experimental endometriosis rats. Network pharmacology approaches showed that imperatorin might regulate inflammatory response and cellular function via primarily affecting PI3K-Akt pathway, Endocrine resistance, Th17 cell differentiation in endometriosis. Moreover, 7 core targets (PIK3CA, AKT1, SRC, MAPK8, MAPK14, ERBB2 and CCND1) resulted from the intersection of KEGG and PPI network topological analysis were used to dock with imperatorin, which indicated that imperatorin could preferably fit in the binding pocket of the above target proteins, except for CCND1. Lastly, imperatorin markedly inhibited the activation of PI3K/Akt/NF-κB pathway via suppressing the phosphorylation levels of PI3K, Akt and p65 in the ectopic endometrium tissue. Significance Our findings revealed that imperatorin is a significant multi-target natural active ingredient for treatment endometriosis.

Background Tumors display a high rate of glucose metabolism and the SLC2A (also known as GLUT) gene family may be central regulators of cellular glucose uptake. However, roles of SLC2A family in mechanism of metabolite communication with immunity in gastric cancer remains unknown. Methods Bioinformatics analysis and IHC staining were used to reveal the expression of SLC2A3 in gastric cancer and the correlation with survival prognosis. Real-time PCR, western blots, OCR, ECAR, lactate production and glucose uptake assays were applied to determine the effect of SLC2A3 on glycolysis reprogramming. We then investigated the consequences of SLC2A3 upregulation or inhibition on aerobic glycolysis, also explored the underlying mechanism. Bioinformatics analysis and in vitro and in vivo research were used to reveal the role of SLC2A3 in macrophage infiltration and transition. Results Here, we show that SLC2A3 acts as a tumor promoter and accelerates aerobic glycolysis in GC cells. Mechanistically, the SLC2A3-STAT3-SLC2A3 feedback loop could promote phosphorylation of the STAT3 signaling pathway and downstream glycolytic targeting genes. Moreover, SLC2A3 potentially contributes to M2 subtype transition of macrophage infiltration in the GC microenvironment. Conclusions SLC2A3 could be used as a prognostic biomarker to determine prognosis and immune infiltration in GC and may provide an intervention strategy for GC therapy.

The antimetabolite 5-fluorouracil (5-FU) is a widely used chemotherapy regimen for the treatment of gastric cancer (GC). However, resistance to 5-FU remains a major drawback in the clinical use. The treatments of anti-tumor chemo-agents recruit tumor associated macrophages (TAMs) which are highly implicated in the chemoresistance development, but the underlying molecular mechanism is unclear. Here, we demonstrate that YAP1 is overexpressed in resistant GC tissues compared to sensitive GC tissues. Further, IL-3 secreted by YAP1-overexpressed GC could skew macrophage polarization to M2-like phenotype and inducing GLUT3-depended glycolysis program. Meanwhile, polarized M2 macrophages enhance 5-FU resistance in tumor cells by secreting CCL8 and activating phosphorylation of JAK1/STAT3 signaling pathway.

Background Thoracic aortic graft infection (TAGI) is a rare and serious complication after surgery for which the treatment is controversial and challenging. Rather than following the traditional surgical strategy of graft replacement and extensive debridement, we have chosen to preserve the graft and cover it by a laparoscopic omental flap. In this article, we describe the clinical manifestation, diagnostic modalities, and treatment of this disease and analyze the role of laparoscopic omental flaps in its treatment. Case presentation We present two cases of thoracic aortic graft infections that had undergone surgical graft replacement for acute Stanford type A dissection. Their clinical manifestation of infection was atypical, with computed tomography suggesting infection of the grafts. Both patients were successfully treated with debridement, laparoscopic omental transposition, and antibiotics. The first case, a 55-year-old male, was found to have an infection at the aortic arch. The second case is a 52-year-old male who was found to have infection at the ascending aorta and arch. Surprisingly, both intraoperative cultures were negative. The infections were brought under control and the patients recovered steadily after surgery. Early follow-up results showed no signs of graft infection. Conclusion These findings suggest that graft replacement for the treatment of TAGI is not always necessary in selected patients. Conservative surgical treatment, including laparoscopic omental transposition, is effective and less invasive for treating TAGI.

Additional file 1 Figure S1. Kaplan–Meier survival curves comparing OS (a–m) and DFS (n–z) between the high and low expression of SLC2A family members in gastric cancer. Figure S2. TIMER database analyzed the expression of SLC2A3 in pan-cancer. Figure S3. (a) Knockdown effectiveness of four siRNAs were tested by western blot. (b) The effects of SLC2A3 perturbation on other GLUT isoforms and HMIT were assessed by RT-PCR. Figure S4. The photo captured by JASPAR to predict the potential binding site in SLC2A3 promoter region by transcriptional factor STAT3. Table S1. Primers and RNA sequences used in this study.

In this paper, we study weighted composition operators on the Hilbert space of Dirichlet series with square summable coefficients. The Hermitianness, Fredholmness and invertibility of such operators are characterized, and the spectra of compact and invertible weighted composition operators are also described.

Trastuzumab is the only target to be approved as the first-line treatment of HER2 positive metastatic gastric cancer, but ubiquitous resistance decreases its therapeutic benefit. In this study, we found HER4, phosphorylation HER4 (p-HER4) and the mesenchymal marker Vimentin increased in trastuzumab-resistant cells (MKN45TR and NCI-N87TR), while epithelial markers expressions in trastuzumab-resistant cell lines and animal models decreased. Additionally, silencing HER4 prevented the epithelial-mesenchymal transition and led to decreased proliferation and migration in vitro and in vivo. The expression of YAP1, a vital downstream interacted target of HER4, decreased when HER4 was knocked down. Interestingly, stimulation of NRG1 could compromise the inhibitory impact and rescue cell survival; whereas, transfection of siYAP1 sensitized trastuzumab-treated cells. Expression analysis of the proteins in patient-derived xenograft model (PDX) mice showed that HER4, p-HER4, YAP1, and Vimentin were clearly upregulated in the trastuzumab-resistant mice compared to mice without trastuzumab resistance. However, HER2 and E-cadherin were downregulated in response to continuous treatment with trastuzumab. These findings elucidated that the central role of the HER4-YAP1 axis in trastuzumab resistance of HER2-positive gastric cancer cells through induction of EMT. Hence, regulating the HER4-YAP1 axis might be a promising strategy for clinical interventions in patients with HER2-positive gastric cancer.

Driver genes conducing to peritoneal metastasis in advanced gastric cancer remain to be clarified. S100A4 is suggested to evolve in metastasis of gastrointestinal cancer, we aim to explore the role of S100A4 plays in metastasis of advanced gastric cancer and the potential mechanism. Transfection of siRNA or cDNA was applied to alter the expression of protein S100A4 and MYH9, investigation of the expression of epithelial and mesenchymal transition (EMT) associated markers was followed. Cell migration assay was used to screen the alteration of migration ability regulated by S100A4 and MYH9. IHC analysis for tissue sample microarray was performed to reveal their relationship with clinical pathological parameters and potential capacity of predicting survival. Consistent overexpression of S100A4 and MYH9 were found in peritoneal metastasis and primary site compared with adjacent normal tissue. Low expression of S100A4 led to increased epithelial markers as wells as decline of mesenchymal makers, while overexpression of S100A4 led to inverse impact. S100A4 expression was closely correlated with increased migration ability and EMT process induced by TGF-β stimulation. Interference of S100A4 led to downregulation of MYH9 and inactivation of Smad pathway through participating in EMT process, which could be reversed by overexpression of MYH9. Moreover, co-expression of S100A4 and MYH9 was identified in tissue microarray and confirmed by immunofluorescence assay. In conclusion, overexpression of S100A4 and downstream molecular MYH9 in advanced gastric cancer predicted poor prognosis; oncogene S100A4 facilitate EMT process induced by TGF-β stimulation, suggesting a potential target in management of peritoneal metastasis of gastric cancer.

We investigate magnetism and optical properties of intrinsic and Mn-doped monolayer CrSi2 using the first-principle methods based on density functional theory. The results show that both monolayer CrSi2 sheets are metallic and ferromagnetic (FM) that hold promise in future 2D magnetic devices. In spite the slight reduction of the total magnetic moment of system after Mn doping in monolayer CrSi2, the formation energies of ferromagnetic CrSi2 are also reduced. So, Mn doping in monolayer CrSi2 can have more promising applications in spintronics and magnetic storage. The optical properties of monolayer CrSi2, including the absorption spectra, reflectivity, refractive index, loss function and dielectric function are also calculated. The intensity of reflectivity in far-infrared ranges is enhanced and real part n of refractive index decreases after Mn doping. The real part n of the refractive index is nearly constant (˜1) beyond 13 eV indicating that monolayer CrSi2 is vacuum like and fully transparent.

On the Hilbert space of Dirichlet series with square summable coefficients, there are no non-normal complex symmetric composition operators induced by non-constant symbols. This is in sharp contrast with the phenomenon on the classical Hardy space over the unit disk.

In this paper, we investigate the -Toeplitzness and asymptotic -Toeplitzness of composition operators and their adjoints on the Hilbert space of Dirichlet series with square summable coefficients. ...

Angiogenesis plays a critical role in the progression and vulnerability of atherosclerotic plaques; however, the orchestration of angiogenesis in atherosclerotic plaque formation remains unclear. The results of microarray analysis, real-time PCR and immunohistochemical analyses showed that Hairy/enhancer of split homologue-1 (Hes-1) expression was significantly decreased, while that of osteopontin (OPN) was increased, in atherosclerotic plaques. Meanwhile, immunofluorescence results demonstrated that both Hes-1 and OPN were expressed in endothelial cells (ECs) of neovessels in atherosclerotic plaques. The results of an in vitro study showed that Hes-1 was downregulated, while OPN was upregulated, in a time- and dose-dependent manner in human umbilical vein endothelial cells (HUVECs) by VEGF treatment. In addition, Hes-1 knockdown was found to have transcriptional promotion effect on OPN expression in HUVECs and enhance OPN-induced angiogenesis in response to VEGF. On the contrary, Hes-1 overexpression inhibited OPN expression in HUVECs and reduced angiogenesis in vitro and in vivo. The results of this study suggest that decreased Hes-1 expression in atherosclerotic plaques exaggerate VEGF-induced angiogenesis by upregulating OPN. Therefore, restoring Hes-1 expression and inhibiting OPN expression may be a promising strategy to prevent vulnerable plaque formation in patients with atherosclerosis.

This study aimed to analyze the early and mid-term outcomes of aortic valve replacement with bovine pericardium in the treatment of aortic valve regurgitation.From January 2015 to March 2018, 36 patients (19 men; mean ± standard deviation [SD] age, 46.70 ± 16.60 years) underwent aortic valve replacement with bovine pericardium. The bovine pericardium was intraoperatively measured and shaped using an Ozaki template, according to the shape and size of the individual patient's aortic valve leaflets. Additional procedures were performed, including ventricular septal defect repair in 5 cases, mitral valve reconstruction in 6 cases, tricuspid valve reconstruction in 6 cases, and coronary artery bypass grafting in 3 cases.There were no perioperative deaths. One elderly patient with postoperative respiratory failure recovered after symptomatic treatment. One patient with frequent ventricular tachycardia after intraoperative cardiac re-jump underwent intra-aortic balloon counterpulsation (IABP), and the IABP device was successfully removed on the second postoperative day. Within the first 6 months of follow-up, there were no death events, no reoperation events, and no additional thromboembolic events. Follow-up echocardiography was performed for 6 months, with average left ventricular ejection fraction of 62.01 ± 3.21%, mean transvalvular pressure gradient of 11.17 ± 4.90 mmHg, and mean aortic valve velocity of 1.60 ± 0.58 m/s. Compared with the preoperative transthoracic echocardiography findings, the results at the six-month follow-up were statistically significant (P0.05). Mild aortic valve regurgitation occurred in 2 patients (5.56%), whereas other patients had no or only minimal aortic valve regurgitation (n = 34, 94.44%). Moderate aortic valve regurgitation occurred in one patient at 9 months after the initial operation. This was found to be due to infective endocarditis, and a biological valve was finally implanted.Aortic valve replacement with bovine pericardium in the treatment of aortic valve regurgitation is feasible, and good early and mid-term results are achieved. Long-term results need to be followed up in the future.

Proliferation and migration of vascular smooth muscle cells (VSMCs) play crucial roles in the development of vascular restenosis. Our previous study showed that CCN4, namely Wnt1 inducible signaling pathway protein 1 (WISP1), significantly promotes proliferation and migration of rat VSMCs, but its mechanism remains unclear. This study aims to investigate whether and how WISP1 stimulates proliferation and migration of human VSMCs. Western blot analysis showed that FBS treatment increased WISP1 protein levels in human VSMCs in a dose-dependent manner. Overexpression of WISP1 using adenovirus encoding WISP1 (AD-WISP1) significantly increased proliferation rate of human VSMCs by 2.98-fold compared with empty virus (EV)-transfected cells, shown by EdU incorporation assay. Additionally, Scratch-induced wound healing assay revealed that adenovirus-mediated overexpression of WISP1 significantly increased cell migration compared with EV-transfected cells from 6h (4.56±1.14% vs. 11.23±2.25%, P

In this paper, we study properties of the topological space of composition operators acting on the space \({\mathcal{H}^{\infty}}\) of Dirichlet series. Especially, we show that there are two compact composition operators which are not in the same path component on \({\mathcal{H}^{\infty}}\). This is in sharp contrast with the classical case where all compact composition operators on \({H^{\infty}}\) of one variable or several variables lie in the same path component.

Background Increasing evidence has shown that gene beta-lactamases (LACTB) has effect on obesity. Recent studies demonstrate that miR-125b-5p is a potential small molecular target to prevent atherosclerosis obliterans which may be inflammation-associated. However, the mechanism underlying miR-125b-5p on arteriosclerosis development, the association between miR-125b-5p and LACTB is still unknown. Methods and results In this study, we found that miR-125b-5p was down-regulated while LACTB was up-regulated in atherosclerotic plaques. Our results showed that LACTB was a potential target of miR-125b-5p based on bioinformatics analyses and dual-luciferase reporter assays. Moreover, miR-125b-5p directly inhibited LACTB protein and mRNA expression by targeting LACTB 3′UTR. Meanwhile, the expression of monocyte chemotactic protein-1 (MCP-1) was decreased by miR-125b-5p mimics treatment in THP-1 macrophages. We also demonstrated that the level of MCP-1 was markedly increased when transfected with LACTB. In addition, the upregulation of MCP-1 expression through miR-125b-5p inhibitors was attenuate by siRNA-LACTB treatment in LPS-stimulated THP-1 macrophages. Conclusions MiR-125b-5p attenuates the secretion of MCP-1 by directly targeting inhibiting LACTB in LPS-stimulated THP-1 macrophages.

Purpose Induction immunosuppression therapy is used to support optimal outcomes in kidney transplantation. This study was to assess the cost-effectiveness of rabbit antithymocyte globulin (r-ATG) versus ATG-Fresenius (ATG-F) in kidney transplantation in the Chinese setting from the perspective of the health care payer. Methods A 2-part survival model was developed, consisting of a short-term part and a long-term part. The short-term part analyzed the first year, using the decision tree, and consisted of the functioning transplant, acute rejection (AR), delayed graft function (DGF), dialysis, and death health states. The long-term part analyzed 2 to 5 years, using Markov model, and consisted of the functioning transplant, chronic dysfunction, recurring primary disease, dialysis, and death health states, with capture of the association between DGF and graft loss. Costs, including drug acquisition and other direct medical costs, were derived from China IQVIA database (formerly known as IMS) hospital database, chart review, and physician interviews. Clinical outcomes and utility were retrieved from published literature. The model calculated quality-adjusted life-years (QALYs) and total costs per patient. Costs and QALYs were discounted at an annual rate of 3.5%. Univariate sensitivity analysis and probability sensitivity analysis (PSA) were conducted to assess the impact of uncertainty of the variables on the results. Findings Patients who received r-ATG had more clinical effectiveness than patients who received ATG-F mainly because of less AR, DGF, and dialysis. The incremental QALY was 0.01 over a 1-year time horizon and 0.0496 over a 5-year time horizon. R-ATG and ATG-F drug costs were ¥10,783 and ¥8409, respectively. However, the total treatment costs of the r-ATG arm were lower than the ATG-F arm because of lower costs related to DGF, AR, dialysis, and adverse events. In total, r-ATG saved ¥5423 over the 1-year and ¥7042 over the 5-year time horizon. R-ATG was dominant with lower total direct medical costs and higher QALYs compared with ATG-F. Both univariate sensitivity analysis and PSA found the robustness of the model results. PSA results indicated that r-ATG was cost-effective compared with ATG-F in 86.81% of the simulations, considering Implications From the perspective of the health care payer, r-ATG should be considered as the preferred treatment agent for induction therapy for Chinese patients undergoing kidney transplantation because of its lower overall medical costs and greater QALYs gained compared with ATG-F. The study was limited by lack of long-term efficacy data among the Chinese population and lack of comprehensive real-world higher quality costs data.