Noninvasive left ventricular pressure-strain myocardial work in patients with well-functioning bicuspid aortic valves and aortic dilation: a preliminary study.

Background: Noninvasive left ventricular pressure-strain myocardial work (MW) is a novel method for evaluating left ventricular function that integrates myocardial deformation and afterload and has certain advantages over global longitudinal strain (GLS). The study aimed to analyze MW in patients with well-functioning bicuspid aortic valve (BAV) and explore the influences of aortic dilation and arterial stiffness on left ventricular function. Methods: A total of 104 patients with well-functioning BAVs and 50 controls were enrolled in our study. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), GLS, and aortic stiffness index were measured. Based on the ascending aortic diameter, patients with BAV were divided into 3 subgroups (nondilated, mildly dilated, and moderately dilated). Results: GWI, GCW, GWW, and aortic stiffness index were significantly increased (P<0.001, P=0.023, P<0.001, and P<0.001, respectively), while GWE and GLS were significantly decreased among patients with BAV compared with controls (all P values <0.001). Patients with BAV and mildly and moderately dilated aortas had an increased GWW and aortic stiffness index but a decreased GWE compared with patients with BAV and nondilated aortas (all P values <0.05); meanwhile, GCW and GLS did not differ among the BAV subgroups (all P values >0.05). GWI was elevated in patients with BAV and moderately dilated aortas compared with patients with BAV and nondilated aortas (P<0.05). On multivariable analysis, the aortic stiffness index was an independent influencer of GWI, GCW, GWW, and GWE (P=0.025, P=0.049, P<0.001, and P=0.001, respectively). The aortic diameter was highly correlated with the aortic stiffness index (r=0.863; P<0.001). Conclusions: MW could assess early myocardial impairment in patients with well-functioning BAV. MW may help to differentiate the detrimental effect of aortic dilation on left ventricular function, whereas GLS may not.

Left atrial strain brings new insights for evaluating early diastolic dysfunction in patients with well-functioning bicuspid aortic valve.

BACKGROUND: Left atrial reservoir strain (LARS) is an early sensor of left ventricular (LV) diastolic dysfunction. Still, the clinical implications of LARS in patients with well-functioning bicuspid aortic valve (BAV) remain unknown. MATERIALS: The study recruited 103 patients with well-functioning BAV and 50 controls with tricuspid aortic valves. LARS, LV global longitudinal strain (LVGLS) and aortic elasticity indices (aortic strain, aortic distensibility and stiffness index) were acquired. This study aimed to analyze the changes of LARS and further explore the influential factors of LARS in patients with well-functioning BAV. RESULTS: Patients with BAV had lower LARS (34.17 ± 4.85 vs. 44.72 ± 6.06 %, P < .001) and LVGLS (20.53 ± 1.28 vs. 22.30 ± .62 %, P < .001), and abnormal aortic elasticity indices (aortic strain:7.14 ± 1.57 vs. 10.99 ± 1.03 %, aortic distensibility: 5.82 ± 1.50 vs. 8.98 ± 2.42 (10-6 cm2 dyne-1 ), and stiffness index: 6.30 ± 2.30 vs. 3.92 ± .98, all P < .05) compared with controls. LARS was associated with LVGLS (r = .799), interventricular septum index (r = -.232), lateral e' (r = .290), septal e' (r = .308), E/e' ratio (r = -.392), aortic strain (r = .829), aortic distensibility (r = .361), and stiffness index (r = -.724) (all P < .05). LVGLS, aortic strain and E/e' ratio were independent influencers of LARS in the multifactorial analysis model (all P < .05). CONCLUSION: In patients with well-functioning BAV, decreased LARS may provide evidence of subclinical LV diastolic function impairment. LARS may be helpful for clinical risk stratification in such a population.

Ursolic acid reduces oxidative stress injury to ameliorate experimental autoimmune myocarditis by activating Nrf2/HO-1 signaling pathway.

Background: Oxidative stress is crucial in experimental autoimmune myocarditis (EAM)-induced inflammatory myocardial injury. Ursolic acid (UA) is an antioxidant-enriched traditional Chinese medicine formula. The present study aimed to investigate whether UA could alleviate inflammatory cardiac injury and determine the underlying mechanisms. Methods: Six-week-old male BALB/c mice were randomly assigned to one of the three groups: Sham, EAM group, or UA intervention group (UA group) by gavage for 2 weeks. An EAM model was developed by subcutaneous injection of α-myosin heavy chain derived polypeptide (α-MyHC peptide) into lymph nodes on days 0 and 7. Echocardiography was used to assess cardiac function on day 21. The inflammation level in the myocardial tissue of each group was compared using hematoxylin and eosin staining (HE) of heart sections and Interleukin-6 (IL-6) immunohistochemical staining. Masson staining revealed the degree of cardiac fibrosis. Furthermore, Dihydroethidium staining, Western blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to determine the mechanism of cardioprotective effects of UA on EAM-induced cardiac injury, and the level of IL-6, Nrf2, and HO-1. Results: In EAM mice, UA intervention significantly reduced the degree of inflammatory infiltration and myocardial fibrosis while improving cardiac function. Mechanistically, UA reduced myocardial injury by inhibiting oxidative stress (as demonstrated by a decrease of superoxide and normalization of pro- and antioxidant enzyme levels). Interestingly, UA intervention upregulated the expression of antioxidant factors such as Nrf2 and HO-1. In vitro experiments, specific Nrf2 inhibitors reversed the antioxidant and antiapoptotic effects of ursolic acid, which further suggested that the amelioration of EAM by UA was in a Nrf2/HO-1 pathway-dependent manner. Conclusion: These findings indicate that UA is a cardioprotective traditional Chinese medicine formula that reduces EAM-induced cardiac injury by up-regulating Nrf2/HO-1 expression and suppressing oxidative stress, making it a promising therapeutic strategy for the treatment of EAM.

Decreased ventricular systolic function in chemotherapy-naive patients with acute myeloid leukemia: a three-dimensional speckle-tracking echocardiography study.

Background: The relationship between acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) and cardiac function is not well established. This study aimed to evaluate whether AML patients exist early myocardial damages prior to chemotherapy and to investigate its association with cardiovascular biomarkers. Methods: Conventional echocardiography and three-dimensional speckle-tracking strain analysis were performed prospectively in 72 acute leukemia (AL) patients before any chemotherapy therapy (of whom 44 were AML patients, 28 ALL patients). The results were compared with those from 58 control group matched for age and gender. Results: There were no significant differences in conventional biventricular systolic function parameters between AL patients and controls. The left ventricular global longitudinal strain (LVGLS) and right ventricular free wall longitudinal strain (RVFWLS) were significantly lower in AL patients (-23.0 ± 1.4% vs. -24.1 ± 1.3% and -27.9 ± 7.1% vs. -33.0 ± 4.6%, respectively, P < 0.001 for all). Compared with ALL patients, AML patients had lower LVGLS and RVFWLS (-22.7 ± 1.3% vs. -23.5 ± 1.6% and -26.2 ± 7.6% vs. -30.4 ± 5.5%, respectively, P < 0.05 for all). LVGLS was lower in ALL patients compared with controls (-23.5 ± 1.6% vs. -24.7 ± 1.4%, P < 0.05), however, there was no difference in right ventricular systolic function parameters between the two groups. LVGLS in AL patients was independently correlated with left ventricular ejection fraction (LVEF) and the absolute number of circulating lymphocytes. Conclusions: Our findings suggest that baseline myocardial systolic function is lower in AL patients than controls. AML patients had lower baseline LVGLS and RVFWLS than controls and ALL patients. The decreased LVGLS is correlated with LVEF and the absolute number of circulating lymphocytes.

New trends in non-pharmacological approaches for cardiovascular disease: Therapeutic ultrasound.

Significant advances in application of therapeutic ultrasound have been reported in the past decades. Therapeutic ultrasound is an emerging non-invasive stimulation technique. This approach has shown high potential for treatment of various disease including cardiovascular disease. In this review, application principle and significance of the basic parameters of therapeutic ultrasound are summarized. The effects of therapeutic ultrasound in myocardial ischemia, heart failure, myocarditis, arrhythmias, and hypertension are explored, with key focus on the underlying mechanism. Further, the limitations and challenges of ultrasound therapy on clinical translation are evaluated to promote application of the novel strategy in cardiovascular diseases.

NaH-promoted one-pot synthesis of 5-amidoimidazoles from arylamines, carbon disulfide and isocyanides.

A novel, convenient and efficient protocol to access functionalized 5-amidoimidazoles is developed via one-pot synthesis from readily available materials of arylamines, carbon disulfide and isocyanides. The transformation was realized at room temperature and provided 5-amidoimidazoles in moderate to good yields in the presence of NaH. In addition, control experiments indicated that the process might be achieved via the base-induced cyclization of activated methylene isocyanides with N,N-disubstituted thioureas that produced from the reaction of amines and carbon disulfide.

Vaginal Microbiota Changes Caused by HPV Infection in Chinese Women.

Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases. After studying 602 unvaccinated Chinese women using 16S rRNA to detect cervical-vaginal microecology, we analyzed the relationship between HPV infection and vaginal microecology including 20 HPV types. In Chinese women, L. gasseri-dominated and L. jensenii-dominated clusters were significantly absence. Microbial alpha diversity was significantly higher in HPV-infected and cervical intraepithelial neoplasia (CIN)-diagnosed groups than in healthy control group. Certain bacteria were associated with HPV infection and CIN, including Streptococcus, Prevotella, Chlamydia, Bifidobacterium, Ralstonia, and Aerococcus. With the development of disease, the proportions of community state type III (CST-III) and CST-IV-B gradually increased, whereas the proportions of CST-I and CST-IV-A gradually decreased. In addition, age was an influential factor for HPV infection. With aging, the probability of HPV infection and the proportion of CST-IV-B increase. In conclusion, our study was a large cross-sectional study that evaluated the relationship between vaginal microbiota and HPV infection, and brought essential comparable data.

An Eco-Friendly Conversion of Aquaculture Suspended Solid Wastes Into High-Quality Fish Food by Improving Poly-ß-Hydroxybutyrate Production.

The aquaculture industry is vital in providing a valuable protein food source for humans, but generates a huge amount of solid and dissolved wastes that pose great risks to the environment and aquaculture sustainability. Suspended solids (in short SS), one of the aquaculture wastes, are very difficult to be treated due to their high organic contents. The bioconversion from wastewater, food effluents, and activated sludge into poly-ß-hydroxybutyrate (PHB) is a sustainable alternative to generate an additional income and could be highly attractive to the agricultural and environmental management firms. However, little is known about its potential application in aquaculture wastes. In the present study, we first determined that 7.2% of SS was PHB. Then, the production of PHB was increased two-fold by the optimal fermentation conditions of wheat bran and microbial cocktails at a C/N ratio of 12. Also, the PHB-enriched SS showed a higher total ammonia nitrogen removal rate. Importantly, we further demonstrated that the PHB-enriched SS as a feed could promote fish growth and up-regulate the expression of the immune-related genes. Our study developed an eco-friendly and simple approach to transforming problematic SS wastes into PHB-enriched high-quality food for omnivorous fish, which will increase the usage efficiency of SS and provide a cheaper diet for aquatic animals.

Synthesis and application of starch-stablized Fe-Mn/biochar composites for the removal of lead from water and soil.

Starch-stablized and Fe/Mn bimetals modified biochar derived from corn straw (SFM@CBC and SFM@CBC-350) were firstly prepared, characterized (FTIR, XRD, SEM, EDS, BET and XPS), and applied in Pb removal from water and soil. SFM@CBC and SFM@CBC-350 displayed highly effective adsorption performance of Pb2+ from wastewater with the maximum adsorption capacity of 170.91 mg g-1 and 190.17 mg g-1, respectively, which were much greater than that of FM@CBC (149.25 mg g-1) and CBC (101.10 mg g-1). Studies of adsorption kinetics, isotherms and thermodynamics indicated that the absorption of Pb2+ by SFM@CBC and SFM@CBC-350 was spontaneous and endothermic reaction, and it was controlled by monolayer chemisorption. The mechanism studies indicated that Pb2+ removal involved with multiple mechanism, including complexation (dominant process confirmed by XPS analysis), physical adsorption, electrostatic attraction, and cation exchange. The reusability test demonstrated that SFM@CBC and SFM@CBC-350 had very good stability and reusability. In addition, in order to further explore Pb removal performance of the modified biochar, SFM@CBC-350 was used in soil-ryegrass pot systems. Compared with the controls, the addition of SFM@CBC-350 reduced Pb content in soil and ryegrass, increased the biomass and total chlorophyll content, reduced the activity of antioxidant enzymes (CAT, SOD, MDA and POD) and ROS fluorescence intensity of ryegrass, thus alleviating Pb stress of ryegrass. Besides, the addition of SFM@CBC-350 could increase the richness and diversity of soil microorganisms, which was beneficial to the growth of ryegrass. Hence, SFM@CBC-350 has the potential of being used as a green, efficient and promising adsorbent in Pb removal from wastewater and soil.

A cross-sectional analysis about bacterial vaginosis, high-risk human papillomavirus infection, and cervical intraepithelial neoplasia in Chinese women.

Bacterial vaginosis (BV) is a genital infection that frequently presents in women infected with human papillomavirus (HPV), but the correlation between BV, HPV and cervical intraepithelial neoplasia (CIN) development is still elusive. We organized a cross-sectional analysis which enrolled 624 participants and obtained 423 samples of vaginal secretions from them, including 193 HPV-negative samples and 230 HR-HPV-positive samples. We used 16S rRNA sequencing to measure the vaginal microbiota diversity in women with different BV, HPV and CIN status, and then calculated risk factors for CIN by logistic regression. We found that the diversity of vaginal microbiota was significantly increased after BV, HPV and BV-infected CIN group. The Observed species and Chao1 index of H.C group showed little difference with normal group, while its Shannon index was considerable higher than normal group. L. iners enriched in HPV infection group compared with others significantly. BV (OR = 0.358; 95% CI = 0.195-0.656; P < .05) and HR-HPV infection (OR = 0.016; 95% CI = 0.004-0.072; P < .001) were risk factors for CIN. In conclusion, we consider BV as a risk factor for CIN. The enrichment of L. iners under HPV infection state may contribute to maintenance of vaginal dysbiosis, and BV infection could facilitate the disturb.

CuCl2·2H2O/TBHP mediated synthesis of ß-enaminones via coupling reaction of vinyl azides with aldehydes.

A facile and efficient oxidative functionalization of vinyl azides with aldehydes furnishing a diverse array of ß-acylated enaminones was developed. The cross coupling was accomplished in the presence of CuCl2·2H2O/TBHP and produced the desired ß-acylated enaminones in a (Z)-stereo-selective and atom-economic manner, which make this protocol particularly attractive. In the transformation, the new C-C and C-N bonds were formed via a one-pot strategy including the process of radical addition and recombination.

Cyprinid herpesvirus 2 infection changes microbiota and metabolites in the gibel carp (Carassius auratus gibelio) midgut.

Cyprinid herpesvirus 2 (CyHV-2) infects gibel carp (Carassius auratus gibelio) and causes severe losses. Microbiota in animal guts involves nutrition intake, development, immunity, and disease resistance. However, the relationship between gibel carp gut microbiota and CyHV-2 infection is not well known. Herein, we analyzed the gut microbiota composition and metabolite profiles in CyHV-2-infected and -uninfected fish using high-throughput sequencing and gas chromatography/mass spectrometry. Results showed that CyHV-2 infection significantly changed gut microbiota and metabolite profiles (p < 0.05). High-throughput sequencing demonstrated that the relative abundance of Aeromonas in the midgut increased dramatically while Cetobacterium decreased. Time-course analysis showed that the number of Aeromonas in the midgut of infected fish increased more than 1,000 times within 5 days post infection. Metabolome analysis illustrated that CyHV-2 infection significantly altered 24 metabolites in the midgut of gibel carp, annotating to the anomaly of digestion and metabolisms of amino acids, carbohydrates, and lipids, such as tryptophan (Trp) metabolism. The Mantel test demonstrated that gut microbiota and metabolite profiles were well related (r = 0.89). Furthermore, Trp metabolism responded to CyHV-2 infection closely was taken as one example to prove the correlation among CyHV-2 infection, metabolites and microbiota in the midgut, and host immunity. Results showed that modulating Trp metabolism could affect the relative abundance of Aeromonas in the midgut of fish, transcription of antiviral cytokines, and CyHV-2 infection. Therefore, we can conclude that CyHV-2 infection significantly perturbed the gut microbiome, disrupted its' metabolic functions, and caused the proliferation of the opportunistic pathogen Aeromonas. This study also suggests that modulation of the gut microbiome will open a therapeutic opportunity to control CyHV-2 infection in gibel carp.

A Unique Role of T Helper 17 Cells in Different Treatment Stages of Multiple Myeloma.

BACKGROUND: T helper 17 (Th17) cells are a subset of CD4-positive T cells, which secrete interleukin 17 and specifically express the retinoic acid receptor-related orphan receptors γt gene. Recently, Studies have shown that the level of Th17 cells in peripheral blood of newly diagnosed multiple myeloma (MM) patients is significantly higher than that of healthy persons. Th17 cells play an important role in the immune microenvironment of MM and interact with tumor cells, osteoclasts, and osteoblasts. Th17 cells might be a potential therapeutic target for MM patients. PATIENTS AND METHODS: In this study, we further tracked the levels of Th17 cells in peripheral blood of 56 patients with MM from newly diagnosed to partial remission to complete remission to relapse and 11 healthy donors. RESULTS: The level of Th17 cells increased further when the disease reached partial remission, decreased to normal level when it reached complete remission, and increased again when the disease recurred. In addition, we also found that in newly diagnosed MM patients, Th17 cell levels fluctuated greatly; not all patients were upregulated, and patients with normal Th17 cell levels had the highest chance of complete remission. CONCLUSION: Th17 cells contribute to the stratification of different treatment stages of MM patients. The level of Th17 cells in patients with newly diagnosed MM is associated with the treatment outcome of complete remission.

Circulating level of Th17 cells is associated with sensitivity to glucocorticoids in patients with immune thrombocytopenia.

Glucocorticoids are a widely recognized first-line therapy for immune thrombocytopenia (ITP). However, some patients are unresponsive to glucocorticoid therapy for reasons that remain unclear. Accumulating evidence suggests that CD4+ T-cell abnormalities play a crucial role in the development of ITP. In the present study, we investigated peripheral blood CD4+ T cells, Th17-associated cytokines, and the mRNA expression level of Th17 transcription factor-RORγt-in patients with newly-diagnosed ITP before glucocorticoid therapy. The study involved 27 newly-diagnosed patients. Th17-cell levels in the peripheral blood of newly-diagnosed ITP patients were associated with responsiveness to glucocorticoid therapy. Newly-diagnosed ITP patients who were not sensitive to glucocorticoid treatment were found to have lower levels of Th17 cells. Quantifying Th17 cells may allow physicians to predict prognosis of glucocorticoid treatment and stratify therapy for those with ITP. This strategy may provide a new approach to the treatment of glucocorticoid-insensitive patients.

Rituximab maintenance therapy for patients with diffuse large B-cell lymphoma: A meta-analysis.

PURPOSE: The addition of rituximab to standard chemotherapy has significantly improved survival in patients with lymphoma. Recently, maintenance therapy with rituximab has been shown to prevent relapse and provide survival benefits for patients with follicular or mantle cell lymphoma. However, the effects of rituximab in patients with diffuse large B-cell lymphoma (DLBCL) remain unclear. Two new studies involving rituximab in the treatment of DLBCL were performed this past year. We performed a meta analysis to evaluate the effects of rituximab maintenance treatment of patients with DLBCL. METHODS: Several databases (PubMed, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) databases were reviewed for relevant randomized controlled trials published prior to May, 2016. Two reviewers assessed the quality of the included studies and extracted data independently. The hazard ratios (HRs) for time-to-event data and relative risks (RRs) for the other data were pooled and estimated. RESULTS: Totally 5 studies including 1740 patients were eligible for the meta-analysis. Compared to the observation group, patients who received rituximab maintenance therapy had significantly improved event-free survival (EFS) (HR = 0.80, 95% CI: 0.65-0.98) and progression-free survival (PFS) (HR = 0.72, 95% CI: 0.54-0.94). However, there was no statistically significant difference in overall survival (OS) (HR = 0.66, 95% CI: 0.27-1.29). A subgroup analysis suggested that male patients may benefit from rituximab maintenance therapy with a better EFS (HR = 0.53, 95% CI: 0.34-0.82-), while this advantage was not observed in female patients (HR = 0.99, 95% CI: 0.64-1.52). CONCLUSIONS: Rituximab maintenance may provide survival benefits beyond that afforded by first- and second-line chemotherapy alone, especially in male patients. However, maintenance rituximab treatment may cause more adverse events. It is recommended that both survival benefits and adverse events should be taken into consideration when making treatment decisions.