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The new coronavirus SARS-CoV-2 has become a global pandemic, which has had a huge impact on the lives of people around the world and has caused huge impacts and losses on global economic development. To now, there is still no effective drug or therapy against coronavirus. A large number of studies have shown that vaccines are the ultimate weapon to eliminate major infectious diseases. The development of new vaccines against new coronaviruses is the best way to prevent new coronavirus infections. In this study, we developed a new vaccine against the new coronavirus by combining our self-developed nano adjuvant loaded with carnosine graphene oxide adjuvant with loaded with CpG molecule and RBD protein antigen. Our results showed that this vaccine can produce high titer anti-SARS-CoV-2 RBD antibody neutralizing SARS-CoV-2 in mice within 2 weeks.

Background Although many studies have reported the effectiveness of nursing interventions on the sexual quality of life of patients with breast cancer, the results have not been synthesized. This study aims to assess the effectiveness of nursing interventions on the sexual quality of life of patients with breast cancer. Review methods A comprehensive search was conducted in 11 databases from inception to October 7, 2021. Studies evaluating the effects of nursing interventions on sexual quality of life were included. Study selection, data extraction, and risk of bias assessment were performed by two independent reviewers. Results This review pooled 38 studies with 3,664 participants. Meta-analysis results showed that nursing interventions significantly improved sexual quality of life, including sexual function (standardized mean difference [SMD] = 0.98, 95% confidence interval [CI] = [0.60–1.37], P < 0.001) and sexual satisfaction (SMD = 0.99, 95% CI = [0.41–1.57], P < 0.001). In addition, depression (SMD = −1.16, 95% CI = [−2.08–−0.24], P = 0.01) and general quality of life (SMD = 0.20, 95% CI = [0.08–0.33], P = 0.002) were significantly improved, but body image (SMD = 0.17, 95% CI = [−0.08–0.41], P = 0.19) and anxiety (SMD = −0.45, 95% CI = [-0.93–0.02], P = 0.06) did not significantly improve. Subgroup analysis showed that nursing interventions had a stronger long-term effect on sexual function (SMD = 1.15, 95% CI = [0.51–1.80], P = P < 0.001) and was more effective in younger patients (SMD = 1.43, 95% CI = [0.63–2.23], P = P < 0.001). Nursing interventions showed a statistically significant short-term effect on sexual satisfaction (SMD = 1.32, 95% CI = [0.44–2.20], P = 0.003) and a significant effect in older patients (SMD = 1.27, 95% CI = [0.46–2.08], P = 0.002). Conclusions Nursing intervention may be an effective way to improve the sexual quality of life of patients with breast cancer. Nursing interventions had a stronger long-term effect on sexual function, and the group with the strongest effect is the younger patients. Nursing interventions showed a significant short-term effect on sexual satisfaction, and older patients had significant improvement in sexual satisfaction.

Abstract Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

Abstract Aims To estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients. Materials and methods 68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR 300 mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), angiotensin II (Ang II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels. Results After 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P

In this work, Inconel 625 alloy is explored regarding high-temperature tensile deformation and fracture behaviors at a strain rate of 0.005–0.01 s−1 under a deformation temperature ranging from 700–800 °C. The subsequent analysis focuses on the impact of deformation parameters on flow and fracture characteristics. The fractured surface reveals that ductile fracture is dominated by the nucleation, growth, and coalescence of microvoids as the primary failure mechanisms. The elevated deformation temperature and reduced strain rate stimulate the level of dynamically recrystallized (DRX) structures, resulting in intergranular fractures. The Arrhenius model and the particle swarm optimization-artificial neural network (PSO-ANN) model are developed to predict the hot tensile behavior of the superalloy. It indicates that the PSO-ANN model exhibits a correlation coefficient (R) as high as 0.9967, surpassing the corresponding coefficient of 0.9344 for the Arrhenius model. Furthermore, the relative absolute error of 9.13% (Arrhenius) and 1.85% (PSO-ANN model) are recorded. The developed PSO-ANN model accurately characterizes the flow features of the Inconel 625 superalloy with high precision and reliability.

PurposeLumbar disc herniation (LDH) is one of the leading causes of low-back pain and results in a series of clinical symptoms, including pain, reflex loss, and muscle weakness. Spinal manipulative therapy (SMT) can relieve pain and promote internal and external stabilization of the lumbar spine. In this study, we investigated whether the brain alterations of LDH patients with SMT were frequency-dependent based on the calculation of Amplitude of Low-Frequency Fluctuations (ALFF) and fractional ALFF (fALFF). Further, we established a cohort of LDH patients to evaluate the contribution of SMT treatments to brain functional reorganization.MethodsA total of 55 participants, including 27 LDH patients and 28 health controls (HCs), were collected. All LDH patients underwent two fMRI scans (before SMT and after the sixth SMT session). To represent LDH-related brain oscillatory activities, we calculated the ALFF and fALFF in the conventional band (0.01–0.08 Hz), the slow-4 band (0.027–0.073 Hz), and the slow-5 band (0.01–0.027 Hz). Moreover, we extracted ALFF and fALFF values in clusters with significant differences to evaluate the SMT effect.ResultsCompared with HCs, the LDH patients before SMT (LDH-pre) exhibited increased fALFF in right lingual gyri in the conventional band, and showed increased fALFF in left Cerebelum_Crus1 in the slow-4 band. We further examined the abnormal brain activities changes before and after the SMT intervention. The ALFF and fALFF values of LDH-pre group were higher than those of the HCs and LDH-pos groups. After SMT, the increased ALFF and fALFF values were suppressed for patients in conventional band and slow-4 band.ConclusionThe present study characterized the altered regional patterns in spontaneous neural activity in patients with LDH. Meanwhile, SMT is an effective treatment of LDH, and we supposed that it might have been involved in modulating dysfunctional brain regions which are important for the processing of pain. The findings of the current study may provide new insights to understand pathological mechanism of LDH.

Abstract Background The prevalence of type 2 diabetes in youth is escalating rapidly. We aimed to evaluate the effects of liraglutide on beta-cell function, metabolic productions of oxidative stress, low grade inflammation compared with metformin in young patients with recent onset type 2 diabetes mellitus. Methods Sixty patients were randomly assigned to receive 8-week liraglutide or metformin treatment. Beta-cell function was assessed by modified beta cell function index (MBCI), early phase of insulin secretion index (ΔI30/ΔG30), proinsuin to insulin ratio (P/I) and the insulin area under the curve (AUCins). The expression of 8-OH-dG and 8-iso-PGF2α and hs-C-reactive protein (hs-CRP) were measured as indications of oxidative stress and low grade inflammation. Results After 8 weeks liraglutide treatment, MBCI, ΔI30/ΔG30, AUCins significantly increased, 8-OH-dG, 8-iso-PGF2α, P/I and hs-CRP remarkably reduced. The differences before and after 8-week liraglutide treatment in ΔMBCI (11.1 [2.81, 43.08] vs 0.00 [− 8.16, 10.47], P = 0.017), ΔLNΔI30/ΔG30 (0.44 [0.04, 0.85] vs − 0.09 [− 0.33, 0.36], P = 0.049), ΔAUCins (117 [− 8, 376] vs − 21 [− 314, 109] mIU/L, P = 0.013), ΔP/I (− 0.05 [− 0.09, − 0.03] vs − 0.02 [− 0.04, 0.01], P = 0.026)were remarkably enhanced compared to those of the metformin therapy. The expression of 8-OH-dG, 8-iso-PGF2α and hs-CRP also decreased after 8-week metformin treatment. Conclusions These data demonstrated that liraglutide administration was more effective on ameliorating beta-cell function than metformin treatment in young patients with new-onset type 2 diabetes mellitus. Both liraglutide and metformin could alleviate the level of oxidative stress and attenuate low grade inflammatory, we speculate this effect may not the main mechanism of beta-cell function improvement by liraglutide in diabetic patients. Trial registration Chinese Clinical Trials registry, chiCTR1800018008, Registered 27 August 2018—retrospectively registered.

BackgroundPreventing relapse of schizophrenic patients is really a challenge. The present study sought to provide more explicit evidence and factors of different grades and weights by a series of step-by-step analysis through χ2 test, logistic regression analysis and decision-tree model. The results of this study may contribute to controlling relapse of schizophrenic patients.MethodsA total of 1,487 schizophrenia patients were included who were 18–65 years of age and discharged from 10 hospitals in China from January 2009 to August 2009 and from September 2011 to February 2012 with improvements or recovery of treatment effect. We used a questionnaire to collect information about relapse and correlative factors during one year after discharge by medical record collection and telephone interview. The χ2 test and logistic regression analysis were used to identify risk factors and high-risk factors firstly, and then a decision-tree model was used to find predictive factors.ResultsThe χ2 test found nine risk factors which were associated with relapse. Logistic regression analysis also showed four high-risk factors further (medication adherence, occupational status, ability of daily living, payment method of medical costs). At last, a decision-tree model revealed four predictors of relapse; it showed that medication adherence was the first grade and the most powerful predictor of relapse (relapse rate for adherence vs. nonadherence: 22.9 vs. 55.7%, χ2 = 116.36, p < 0.001). The second grade factor was occupational status (employment vs. unemployment: 19.7 vs. 42.7%, χ2 = 17.72, p < 0.001); the third grade factors were ability of daily living (normal vs. difficult: 28.4 vs. 54.3%, χ2 = 8.61, p = 0.010) and household income (household income ≥ 3000 RMB vs.

Abstract Background It has been suggested that liraglutide could have an impact on glucose and lipid metabolism disorder and adhesion molecule activation, which may play important roles in the vascular damage of diabetes. In this study, we examined the effects of liraglutide versus metformin on non-esterified free fatty acids, beta-cell insulin secretion, and adhesion molecule levels in patients with recent-onset type 2 diabetes mellitus. Methods In this study, 60 patients newly diagnosed with type 2 diabetes mellitus (mean age 33.97 ± 5.67 years) were randomly assigned to receive once-daily subcutaneous liraglutide or oral metformin. Before the study and after the 8-week treatment period, a 75 g oral glucose tolerance test was performed. Plasma glucose, lipids and lipoprotein, plasma insulin, glycaemic and insulin responses, non-esterified free fatty acids (NEFA), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were evaluated. Results After 8 weeks, 120 min of NEFA (155 ± 125 vs 99 ± 73 µmol/L, P = 0.026) and the levels of sVCAM-1 (465 ± 136 vs 382 ± 131 ng/ml, P = 0.013) significantly decreased, while the early phase insulin secretion index (24.94 [7.78, 38.89] vs. 31.13 [17.67, 59.09], P = 0.031), fasting plasma insulin (104 [51, 123] vs 113 [54, 171] mIU/L, P = 0.015), 60 min plasma insulin (326 [165, 441] vs 471 [334, 717] mIU/L, P = 0.005), 120 min plasma insulin (401 [193, 560] vs 500 [367, 960] mIU/L, P = 0.047), and insulin area under the curve (AUCins) (648 [321, 742] vs 738 [451, 1118] mIU/L, P = 0.005) remarkably increased for patients in the liraglutide treatment group. The levels of sVCAM-1 dramatically decreased after 8 weeks of liraglutide treatment (503 ± 182 vs 382 ± 131 ng/ml, P = 0.046) compared to that of the metformin treatment group. At the same time, the differences before and after liraglutide treatment in 120 min of NEFA (− 32 [− 96, − 5] vs 5 [− 35, 38] µmol/L, P = 0.033) and AUCins (738 [451, 1118] vs 594 [357, 1216] mIU/L, P = 0.014) were remarkably enhanced compared to that of the metformin therapy. Nevertheless, there were no significant differences in fasting NEFA after liraglutide or metformin treatment. The reduction of 120 min NEFA (ΔNEFA) was positively correlated with the decrease of sVCAM-1 (ΔsVCAM-1) after 8 weeks of liraglutide treatment (r = 0.523, P = 0.003). Conclusions Our results demonstrate that liraglutide administration is more effective than metformin in reducing 120 min NEFA and suppressing sVCAM-1 levels for recent-onset type 2 diabetes mellitus. We suggest that this outcome may be because liraglutide is associated with potentiating insulin secretion capacity, inhibiting vascular inflammatory cytokines, and antagonizing atherosclerosis.

The hot deformation characteristics of a GH4169 superalloy are investigated at the temperature and strain rate ranges of 1193–1313 K and 0.01–1 s−1, respectively, through Gleeble-3500 simulator. The hot deformed microstructures are analyzed by optical microscopy (OM), transmission electron microscopy (TEM), and electron backscattered diffraction (EBSD) technology. The effects of deformation parameters on the features of flow curves and annealing twins are discussed in detail. It is found that the shapes of flow curves are greatly affected by the deformation temperature. Broad peaks appear at low deformation temperatures or high strain rates. In addition, the evolution of annealing twins is significantly sensitive to the deformation degree, temperature, and strain rate. The fraction of annealing twins first decreases and then rises with the added deformation degree. This is because the initial annealing twin characters disappear at the relatively small strains, while the annealing twins rapidly generate with the growth of dynamic recrystallized grains during the subsequent hot deformation. The fraction of annealing twins is relatively high when the deformation temperature is high or the strain rate is low. In addition, the important role of annealing twins on dynamic recrystallization (DRX) behaviors are elucidated. The obvious bulging at initial twin boundaries, and the coherency of annealing twin boundaries with dynamic recrystallized grain boundaries, indicates that annealing twins can motivate the DRX nucleation during the hot deformation.

AIM: To detect early glaucoma by optical coherence tomography (OCT) posterior pole asymmetry analysis. METHODS: Totally 39 eyes from 39 healthy subjects, 40 eyes from 40 mild glaucoma patients, 33 eyes from 33 moderate glaucoma patients and 41 eyes from severe glaucoma patients were included in this study. All subjects underwent posterior pole asymmetry analysis (PPAA) of OCT and the posterior pole area was divided into three zones. Means, standard deviations and 95% confidence intervals of each zone asymmetry in control group were assessed. Retina thickness asymmetry (RTA) of different stage of glaucoma were compared for each zone, and receiver operating characteristic (ROC) curves were made to test the efficacy of strategies using different zones to discriminate glaucomatous eyes from the healthy ones. RESULTS: In a healthy population, RTA of the centre zone showed the minimal mean value (3.085 μm), standard deviation (1.756), and the narrowest 95% confidence interval (from 2.360 to 3.810 μm). It was only in the center zone that RTA exhibited significant difference between control and moderate glaucoma group (P

The incidence of ischemic stroke in patients with diabetes is increasing. While brachial-ankle pulse wave velocity (BaPWV) and ankle-brachial index (ABI) are known to be associated with ischemic cardiovascular and cerebrovascular diseases, whether these measures predict the risk of ischemic cerebrovascular disease in diabetic patients remains unclear. 117 patients with type 2 diabetes were enrolled in this study. According to the results of head magnetic resonance imaging, the patients were divided into a diabetes-only group (n = 55) and a diabetes and ischemic stroke group (n = 62). We then performed ABI and BaPWV examinations for all patients. Compared with the diabetes-only group, we found decreased ABI and increased BaPWV in the diabetes and ischemic stroke group. Multivariate logistic regression analyses revealed that BaPWV and ABI were risk factors for ischemic stroke in patients with type 2 diabetes. Our findings indicate that decreased ABI and increased BaPWV are objective indicators of increased risk of ischemic stroke in patients with type 2 diabetes.

Purpose: Investigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes. Methods: Patients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs. Results: In comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LOMFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs. Conclusion: The present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients. [ABSTRACT FROM AUTHOR]

Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model.Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively.Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with the VP group. .Immunohistochemistry analysis revealed that NF-κB and MMP expression was reduced in the MSC and SP groups compared to the VP group. Cell apoptosis decreased significantly in both the MSC and SP groups in comparison to the VP group. TSG-6 mRNA and protein expression were higher in the plaques of the MSC group compared to the VP and SP groups.Our study results suggest that MSC transplantation can effectively stabilize vulnerable plaques in atherosclerotic rabbits. This may potentially offer a new clinical application of MSC in atherosclerosis.

Background. Recent studies suggest that mutation of the slow delayed rectifier potassium channel (IKs) contributes to familial atrial fibrillation (FAF). In the current study, we identified common genetic variants of KCNQ1 and explored the potential association between KCNQ1 polymorphism with lone AF (LAF). Methods. Clinical data and blood samples were collected from 190 Han Chinese patients with sporadic AF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified six known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 190 LAF patients and 190 healthy controls. Results. One of the SNPs in KCNQ1 was strongly associated with LAF; significant allelic association was detected rs59233444 (P=0.013, OR=1.469, 95% confidence interval (CI): 1.083–1.993). A multiple regression analysis indicated that rs59233444 is an independent risk factor for LAF. Twelve new variants were identified in KCNQ1, including one in the 5′-UTR, two in the 3′-UTR, six in introns, two synonymous substitutions, and one missense substitution. Variants c.1009C>T, c.1860C>T, and c.+2285C>T were not present in the 190 controls, and the others were identified in controls at various frequencies. Conclusions. rs59233444, a common SNP but not mutation in the coding regions of the KCNQ1 gene, is a risk factor for LAF in Chinese Han population.

A new generation method for spatial and temporal correlated multiple-input multiple-output (MIMO) Nakagami fading channel is proposed, which has low complexity and is applicable for arbitrary fading parameters and prespecified correlation coefficients of different subchannel. The new scheme can be divided into two steps: (1) generate independent Nakagami fading sequences for each subchannel based on a novel rejection method; (2) introduce the temporal and spatial correlation based on the relationships between Rayleigh, Gamma, and Nakagami random processes. The analysis and simulation results show that the proposed simulator has a good agreement with the theoretical model on fading envelope distribution, spatial-temporal correlation characteristic.

The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co-expression analysis. The microarray dataset associated with HCM (E-GEOD-36961) was obtained from the European Molecular Biology Laboratory-European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co-expression networks for informative pathways, and a weight value was assigned to each pathway. Differential pathways were extracted based on weight threshold, which was calculated using a random model. In order to assess whether the co-expression method was feasible, it was compared with traditional pathway enrichment analysis of differentially expressed genes, which were identified using the significance analysis of microarrays package. A total of 1,074 informative pathways were screened out for subsequent investigations and their weight values were also obtained. According to the threshold of weight value of 0.01057, 447 differential pathways, including folding of actin by chaperonin containing T-complex protein 1 (CCT)/T-complex protein 1 ring complex (TRiC), purine ribonucleoside monophosphate biosynthesis and ubiquinol biosynthesis, were obtained. Compared with traditional pathway enrichment analysis, the number of pathways obtained from the co-expression approach was increased. The results of the present study demonstrated that this method may be useful to predict marker pathways for HCM. The pathways of folding of actin by CCT/TRiC and purine ribonucleoside monophosphate biosynthesis may provide evidence of the underlying molecular mechanisms of HCM, and offer novel therapeutic directions for HCM. [ABSTRACT FROM AUTHOR]

Purpose: Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial. Materials and Methods: Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared. Results: Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and allcause mortality rates were similar. Conclusion: Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure. [ABSTRACT FROM AUTHOR]

The flow softening behaviors of a nickel-based superalloy with δ phase are investigated by hot compression tests over wide ranges of deformation temperature and strain rate. Electron backscattered diffraction (EBSD), optical microscopy (OM), and scanning electron microscopy (SEM) are employed to study the flow softening mechanisms of the studied superalloy. It is found that the flow softening behaviors of the studied superalloy are sensitive to deformation temperature and strain rate. At high strain rate and low deformation temperature, the obvious flow softening behaviors occur. With the increase of deformation temperature or decrease of strain rate, the flow softening degree becomes weaken. At high strain rate (1s-1), the flow softening is mostly induced by the plastic deformation heating and flow localization. However, at low strain rate domains (0.001-0.01s-1), the effects of deformation heating on flow softening are slight. Moreover, the flow softening at low strain rates is mainly induced by the discontinuous dynamic recrystallization and the dissolution of δ phase (Ni3Nb). [ABSTRACT FROM AUTHOR]

Urapidil has been proposed to be an effective vasodilator for the treatment of acute decompensated heart failure (ADHF); however, its effect on cardiac function, as compared with that of nitroglycerin, in elderly patients with hypertension and ADHF has yet to be determined. In the present study, a multicenter, open-label clinical trial was performed, in which 120 elderly patients with hypertension and ADHF were randomly assigned to the treatment (50-400 μg/min intravenous urapidil) or control group (5-40 μg/min intravenous nitroglycerin). The dosages of the medications were adjusted according to the blood pressure of the patients. The systolic and diastolic blood pressure, heart rate and serum level of N-terminal pro B-type natriuretic peptide (NT-proBNP) were evaluated at hospital admission and at days 1, 2, 3 and 7 after treatment. In addition, the left ventricular function was assessed by measuring the left ventricular ejection fraction (LVEF) and left ventricular end-diastolic volume at hospital admission and at days 2 and 7 after treatment. The results indicated that intravenous administration of urapidil and nitroglycerin were effective in lowering the blood pressure and heart rate within 7 days, with no significant differences observed between the two groups (P>0.05). By contrast, greater reduction in the serum NT-proBNP level (2,410.4±546.1 vs. 4,234.1±876.4 pg/ml; P<0.05) and greater improvement in the LVEF (55.3±3.4 vs. 45.2±2.4%; P<0.05) were observed in the urapidil-treated group, as compared with the nitroglycerin-treated group. No adverse events were reported during the treatment period in the two groups. The clinical outcomes at 6 months following discharge were evaluated and were not found to be significantly different between the two groups. In conclusion, the present results of the present study suggested that urapidil was as effective as nitroglycerin in controlling blood pressure and heart rate and was more effective in improving cardiac systolic function in elderly patients with hypertension and ADHF. [ABSTRACT FROM AUTHOR]

Scinderin is a Ca2+-dependent filamentous actin (F-actin) severing and capping protein, which has a key role in regulated secretion. However, little is known regarding the function and mechanism of scinderin in human carcinoma development and progression. In the present study, the biological function of scinderin was investigated using a cell proliferation assay, flow cytometric analysis and a Transwell assay in highly tumorigenic and the metastatic human gastric cancer cell line SGC-7901 transfected with scinderin-small hairpin RNA lentivirus. The changes in the expression of epithelial-mesenchymal transition (EMT) markers were also investigated. The results indicated that scinderin knockdown effectively suppressed proliferation, reduced migration and arrested the cell cycle of the SGC-7901 cells at G2/M phase. Furthermore, scinderin knockdown altered the expression of EMT markers; the expression of E-cadherin was significantly upregulated, along with an evident decrease in N-cadherin and β-catenin expression. In conclusion, the present study suggested that suppression of scinderin impaired proliferation and migration of gastric cancer SGC-7901 cells and attenuates its EMT process. Scinderin may therefore be a potential target for tumor EMT and therapy against gastric cancer. [ABSTRACT FROM AUTHOR]

For the first two equations of the Volterra lattice hierarchy and the first two equations of its non-autonomous (non-isospectral) extension, we present Riccati systems for functions cj(t), , such that an expression in terms of Hankel determinants built from them solves these equations on the right half of the lattice. This actually achieves a complete linearization of these equations of the extended Volterra lattice hierarchy. [ABSTRACT FROM AUTHOR]

In this paper, we present a generalized Toeplitz determinant solution for the generalized Schur flow and propose a mixed form of the two known relativistic Toda chains together with its generalized Toeplitz determinant solution. In addition, we also give a Hankel type determinant solution for a nonisospectral Toda lattice. All these results are obtained by technical determinant operations. As a bonus, we finally obtain some new combinatorial numbers based on the moment relations with respect to these semi-discrete integrable systems and give the corresponding combinatorial interpretations by means of the lattice paths. [ABSTRACT FROM AUTHOR]

By introducing some special bi-orthogonal polynomials, we derive the so-called discrete hungry quotient-difference (dhQD) algorithm and a system related to the QD-type discrete hungry Lotka–Volterra (QD-type dhLV) system, together with their Lax pairs. These two known equations can be regarded as extensions of the QD algorithm. When this idea is applied to a higher analogue of the discrete-time Toda (HADT) equation and the quotient–quotient-difference (QQD) scheme proposed by Spicer, Nijhoff and van der Kamp, two extended systems are constructed. We call these systems the hungry forms of the higher analogue discrete-time Toda (hHADT) equation and the quotient-quotient-difference (hQQD) scheme, respectively. In addition, the corresponding Lax pairs are provided. [ABSTRACT FROM AUTHOR]

Abstract Background Herpes simplex keratitis (HSK) is a rare and sight-threatening complication following refractive surgery. SmartSurfACE surgery is the result of combining transepithelial photorefractive keratectomy (trans-PRK) with Smart Pulse Technology (SPT) to diminish surface irregularities of the residual stromal bed after surgery with less pain, faster re-epithelialization, and better postoperative visual acuity. In this article, we report the first case of HSK following SmartSurf ACE without history of herpetic eye disease. Case presentation A 21-year-old woman underwent bilateral SmartSurfACE without history of clinical herpetic infection, active eye disease, or systemic disease. Mild superficial punctate keratitis occurred on the tenth postoperative day. The condition was not improved by ophthalmic drugs of anti-inflammation or epithelial healings. Dendritic corneal ulcer appeared within one month, which is the commonly recognized clinical manifestation of herpes simplex keratitis. The patient was managed with topical and systemic antiviral agents. After nine days of antiviral therapy, the lesion healed up, remaining mild stromal scarring in both eyes ultimately. Conclusion Herpes simplex keratitis is a rare but sight-threatening complication following refractive surgery. For the ocular irritation symptoms of postoperative patients, we should consider the possibility of HSK and give timely treatment.

Abstract To evaluate the effect of SGLT2 inhibitor (SGLT2i) on albuminuria, nephrin (NPH) and transforming-growth-factor-beta1 (TGF-β1) levels in urine and low-grade inflammation in type 2 diabetes (T2D) patients. A randomized, blank-controlled clinical trial included 68 T2D patients and 10 controls. Based on the urinary albumin-to-creatinine ratio (UACR), 68 diabetic patients were stratified into three levels, UACR

Abstract Poly‐ADP‐ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA‐deficient tumors. However, over 40% of BRCA‐deficient patients fail to respond to PARPi. Here, we report that thioparib, a next‐generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi‐sensitive and ‐resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1‐dependent DNA damage and replication stress, causing S‐phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR‐mediated DNA repair while increasing RAD51 foci formation. Notably, the on‐target inhibition of PARP7 by thioparib‐activated STING/TBK1‐dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome‐scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next‐generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier‐generation PARPi.