[Synthesis and tissue distribution of bufadienolides in Bufo bufo gargarizans].

This study explored the biosynthesis of bufadienolides(BDs) in Bufo bufo gargarizans to solve the dilemma of the decreasing resources of B. bufo gargarizans and provide a theoretical basis for the sustainable utilization of the resources. Ultra-high performance liquid chromatography-Orbitrap-mass spectrometry(UHPLC-Orbitrap-MS) was employed to detect the synthesis sites of BDs in B. bufo gargarizans, and the results were verified by desorption electrospray ionization-mass spectrometry imaging(DESI-MSI) and homogenate incubation experiments. BDs in B. bufo gargarizans had the highest content in the liver and the highest concentration in the gallbladder, in addition to the parotid gland and skin, which suggested that the liver could synthesize BDs. The results of DESI-MSI also showed that BDs were mainly enriched in the liver rather than the immature parotid gland. The incubation experiment of liver homogenates demonstrated the liver of B. bufo gargarizans had the ability to synthesize BDs. This study showed that the liver was a major organ for the synthesis of BDs in B. bufo gargarizans during metamorphosis, development, and growth, which provided strong theoretical support for the biosynthesis of BDs and the sustainable utilization of B. bufo gargarizans resources.

[Evaluation of efficacy of Dihuang Baoyuan Granules for diabetes mellitus and composition and in vivo distribution analysis based on UHPLC-LTQ-Orbitrap MS].

Dihuang Baoyuan Granules is a prescription endorsed by HU Tianbao, a renowned and elderly Chinese medicine practitioner from Beijing, and has demonstrated definite clinical efficacy. The composition of this prescription is intricate as it includes 7 distinct herbal medicines. This study aims to analyze the chemical composition of Dihuang Baoyuan Granules, evaluate its efficacy in the treatment of diabetes and analyze the distribution of the drug components in the plasma, liver, and kidney after administration. The findings will serve as a reference for future research on pharmacodynamic substances of this prescription. UHPLC-LTQ-Orbitrap MS was employed to analyze the main chemical components of Dihuang Baoyuan Granules. A Waters ACQUITY Premier HSS T3 column(2.1 mm×100 mm, 1.8 µm) was used for chromatographic separation with 0.1% formic acid(A)-acetonitrile(B) as the mobile phases in a gradient elution at a flow rate of 0.3 mL·min~(-1). Electrospray ionization(ESI) source was used to acquire data in positive and negative ion modes. Furthermore, a rat model of diabetes mellitus was established by feeding with a high-sugar high-fat diet, and injection with streptozocin at a dose of 35 mg·kg~(-1), and the modeled rats were then administrated with Dihuang Baoyuan Granules. The fasting blood glucose, hemoglobin A1c, and other relevant indicators were measured, and the substances present in the plasma, liver, and kidney were identified. By reference to quasi-molecular ions, MS/MS fragment ions, MS spectra of reference substances, and compound information in available reports, 191 components were identified in Dihuang Baoyuan Granules, including 29 alkaloids, 24 flavonoids, 22 organic acids, 16 amino acids, 12 terpenes, 11 steroid saponins, 9 sugars, 8 phenylethanoid glycosides, 8 nucleosides, 2 phenylpropanoids, and 49 others compounds. Eighty-three chemical components were identified in rat plasma, 109 in the liver, and 98 in the kidney. Component identification and characterization of Dihuang Baoyuan Granules in vitro and in vivo provide efficacy information and guidance for the basic research on the pharmacodynamic substances and further clinical application of this prescription.

Design, synthesis and neuraminidase inhibitory activity of 4-methyl-5-(3-phenylacryloyl) thiazoles.

A series of 4-methyl-5-(3-phenylacryloyl)thiazoles based on chalcones were designed, synthesized and evaluated for their influenza neuraminidase (NA) inhibitory activity in vitro. A preliminary structure-activity relationship (SAR) analysis showed that thiazoles bearing amide had greater potency. It also showed that mono-hydroxyl group at 4-position on phenyl ring was more effective than other electron-releasing groups or electron-withdraw groups. Compounds A2 and A26 were more potent against NA with IC50 values of 8.2 ± 0.5 µg/mL and 6.2 ± 1.4 µg/mL, respectively. Molecular docking study demonstrated that thiazoles skeleton was benefit for the NA inhibitory activity.

Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma.

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment.

Developing and validating a Chinese multimorbidity-weighted index for middle-aged and older community-dwelling individuals.

OBJECTIVE: To develop and validate an index to quantify the multimorbidity burden in Chinese middle-aged and older community-dwelling individuals. METHODS: We included 20,035 individuals aged 45 and older from the China Health and Retirement Longitudinal Study (CHARLS) and 19,297 individuals aged 65 and older from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Health outcomes of physical functioning (PF), basic and instrumental activities of daily living (ADL and IADL) and mortality were obtained. Based on self-reported disease status, we calculated five commonly used western multimorbidity indexes for CHARLS baseline participants. The one that predicted the health outcomes the best was selected and then modified through a linear mixed model using the repeated individual data in CHARLS. The performance of the modified index was internally and externally evaluated with CHARLS and CLHLS data. RESULTS: The multimorbidity-weighted index (MWI) performed the best among the five indexes. In the modified Chinese multimorbidity-weighted index (CMWI), the weights of the diseases varied greatly (range 0.2-5.1). The top three diseases with the highest impact were stroke, memory-related diseases and cancer, corresponding to weights of 5.1, 4.3 and 3.4, respectively. Compared with the MWI, the CMWI showed better model fits for PF and IADL with larger R2 and smaller Akaike information criterion, and comparable prediction performances for ADL, IADL and mortality (e.g. the same predictive accuracy of 0.80 for ADL disability). CONCLUSION: The CMWI is an adequate index to quantify the multimorbidity burden for Chinese middle-aged and older community-dwelling individuals. It can be directly computed via disease status examined in regular community health check-ups to facilitate health management.

Machine learning to predict mesenchymal stem cell efficacy for cartilage repair.

Inconsistent therapeutic efficacy of mesenchymal stem cells (MSCs) in regenerative medicine has been documented in many clinical trials. Precise prediction on the therapeutic outcome of a MSC therapy based on the patient's conditions would provide valuable references for clinicians to decide the treatment strategies. In this article, we performed a meta-analysis on MSC therapies for cartilage repair using machine learning. A small database was generated from published in vivo and clinical studies. The unique features of our neural network model in handling missing data and calculating prediction uncertainty enabled precise prediction of post-treatment cartilage repair scores with coefficient of determination of 0.637 ± 0.005. From this model, we identified defect area percentage, defect depth percentage, implantation cell number, body weight, tissue source, and the type of cartilage damage as critical properties that significant impact cartilage repair. A dosage of 17 - 25 million MSCs was found to achieve optimal cartilage repair. Further, critical thresholds at 6% and 64% of cartilage damage in area, and 22% and 56% in depth were predicted to significantly compromise on the efficacy of MSC therapy. This study, for the first time, demonstrated machine learning of patient-specific cartilage repair post MSC therapy. This approach can be applied to identify and investigate more critical properties involved in MSC-induced cartilage repair, and adapted for other clinical indications.

Three Unusual Sesquiterpenes with Distinctive Ring Skeletons from Daphne penicillata Uncovered by Molecular Networking Strategies.

Daphnenoids A-C (1-3), three unusual sesquiterpenes with distinctive ring skeletons, together with a biogenetically related daphnenoid D (4) were obtained from the herb of Daphne penicillata by molecular networking strategies. Daphnenoid A (1) possesses a unique caged tetracyclo [5.3.2.01,6.04,11] dodecane scaffold by unexpected cyclizations of C-1/C-11 and C-2/C-14. Daphnenoids B and C (2 and 3) were the first discovered natural sesquiterpenes with unique 5/5 spirocyclic systems in nature. Their structures were determined by NMR spectroscopic analysis, computer-assisted structure elucidation methods, quantum chemical calculations, and X-ray diffraction. A hypothetical biogenetic pathway begins with typical guaiane sesquiterpene (a), including a key intermediate (4) was proposed. Daphnenoids B and C (2 and 3) exhibited potential inhibitory activities on the production of NO against LPS-induced BV2 microglial cells.

High and Tunable Proton Conduction in Six 3D-Substituted Imidazole Dicarboxylate-Based Lanthanide-Organic Frameworks.

Six isostructural three-dimensional (3D) Ln(III)-organic frameworks, {[Ln2(HMIDC)2(µ4-C2O4)(H2O)3]·4H2O}n [LnIII = GdIII (1), EuIII (2), SmIII (3), NdIII (4), PrIII (5), and CeIII (6)], have been fabricated by using a multifunctional ligand of 2-methyl-1H-imidazole-4,5-dicarboxylic acid (H3MIDC). Ln-metal-organic frameworks (MOFs) 1-6 present 3D structures and possess abundant H-bonded networks between imidazole-N atoms and coordinated and free water molecules. All the six Ln-MOFs demonstrate humidity- and temperature-dependent proton conductivity (σ) having the optimal values of 2.01 × 10-3, 1.40 × 10-3, 0.93 × 10-3, 2.25 × 10-4, 1.11 × 10-4, and 0.96 × 10-4 S·cm-1 for 1-6, respectively, at 100 °C/98% relative humidity, in the order of CeIII (6) < PrIII (5) < NdIII (4) < SmIII (3) < EuIII (2) < GdIII (1). In particular, the σ for 1 is 1 order of magnitude higher than that for 6, and it enhances systematically according to the decreasing order of the ionic radius, indicating that the lanthanide-contraction tactics can effectively regulate the proton conductivity while retaining the proton conduction routes. This will offer valuable guidance for the acquisition of new proton-conducting materials. In addition, the outstanding water stability and electrochemical stability of such Ln-MOFs will afford a solid material basis for future applications.

Exchange Bias in Magnetic Topological Insulator Superlattices.

Magnetic doping and proximity coupling can open a band gap in a topological insulator (TI) and give rise to dissipationless quantum conduction phenomena. Here, by combining these two approaches, we demonstrate a novel TI superlattice structure that is alternately doped with transition and rare earth elements. An unexpected exchange bias effect is unambiguously confirmed in the superlattice with a large exchange bias field using magneto-transport and magneto-optical techniques. Further, the Curie temperature of the Cr-doped layers in the superlattice is found to increase by 60 K compared to a Cr-doped single-layer film. This result is supported by density-functional-theory calculations, which indicate the presence of antiferromagnetic ordering in Dy:Bi2Te3 induced by proximity coupling to Cr:Sb2Te3 at the interface. This work provides a new pathway to realizing the quantum anomalous Hall effect at elevated temperatures and axion insulator state at zero magnetic field by interface engineering in TI heterostructures.

Vogesella urethralis sp. nov., isolated from human urine, and emended descriptions of Vogesella perlucida and Vogesella mureinivorans.

A novel Vogesella strain, YM-1T, was recovered from human urine in PR China in 2017. Cells of strain YM-1T were Gram-stain-negative, rod-shaped, aerobic, motile, non-spore-forming and poly-ß-hydroxybutyrate-accumulating. The strain contained C16:1ω6c/C 16:1ω7c, C16:0 and C18:0ω7c as major fatty acids; phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified phospholipid as major polar lipids; and ubiquinone-8 as the predominant respiratory quinone. Comparison of 16S rRNA gene sequences indicated that this strain had highest similarities to Vogesella perlucida DS-28T (98.8 %) and Vogesella mureinivorans 389T (98.1 %). The results of phylogenetic analysis based on the 16S rRNA gene sequences revealed that the novel strain was clustered and well separated with V. perlucida DS-28T and V. mureinivorans 389T within the genus Vogesella. The average nucleotide identity (ANI) and amino acid identity (AAI) analyses showed that this strain was not identified as V. perlucida DS-28T or V. mureinivorans 389T, with values well below the threshold limit for species demarcation (ANI <88.1 %, AAI <88.6 %). Based on the above results, strain YM-1T is proposed to be a novel species of the genus Vogesella with the name Vogesella urethralis sp. nov. (YM-1T=NBRC 113779=CGMCC 1.17135).

Isoliquiritin promote angiogenesis by recruiting macrophages to improve the healing of zebrafish wounds.

Licorice is a widely used herbal medicine for the treatment of various diseases in southern Europe and parts of Asia. It has been reported that the isoliquiritin (ISL) from Glycyrrhiza root has the activity of promoting angiogenesis. The purpose of this study was to investigate the effect of ISL on the wound healing activity of zebrafish and its mechanism. 6-month-old zebrafish were injured in the skin (2 mm in diameter) and then treated with ISL. By measuring wound size and by histological examination, we found that ISL improved wound healing. In addition, 4-day-old zebrafish embryos of double transgenic line [Tg(fli-1:EGFP)]/[Tg(mpeg:mCherry)] were suffered from tissue traumas and then treated with ISL. Through fluorescent microscopy, we found that ISL promoted macrophage recruitment and angiogenesis in the wound area. Through qPCR analysis, we found that ISL up-regulated the expression of genes related to inflammation and angiogenesis in zebrafish embryos. These results showed that ISL could promote inflammatory response and angiogenesis, which played key roles in promoting wound healing. Therefore, ISL can be used as a promising candidate to promote wound healing.

Poor cardiovascular health status among Chinese women.

BACKGROUND: Systematic investigation and analysis of cardiovascular health status (CVHS) of Chinese women is rare. This study aimed to assess CVHS and atherosclerotic cardiovascular disease (ASCVD) burden in the Chinese women physicians (CWP) and community-based non-physician cohort (NPC). METHODS: In this prospective, multicenter, observational study, CVHS using the American Heart Association (AHA) defined 7 metrics (such as smoking and fasting glucose) and ASCVD risk factors including hypertension, hyperlipidemia and type-2 diabetes were evaluated in CWP compared with NPC. RESULTS: Of 5832 CWP with a mean age of 44 ± 7 years, only 1.2% achieved the ideal CVHS and 90.1% showed at least 1 of the 7 AHA CVHS metrics at a poor level. Total CVHS score was significantly decreased and ASCVD risk burden was increased in postmenopausal subjects in CWP although ideal CVHS was not significantly influenced by menopause. Compared to 2596 NPC, fewer CWP had ≥ 2 risk factors (8% vs. 27%, P < 0.001); CWP scored significantly higher on healthy factors, a composite of total cholesterol, blood pressure, fasting glucose (P < 0.001), but, poorly on healthy behaviors (P < 0.001), specifically in the physical activity component; CWP also showed significantly higher levels of awareness and rates of treatment for hypertension and hyperlipidemia, but, not for type-2 diabetes. CONCLUSION: Chinese women's cardiovascular health is far from ideal and risk intervention is sub-optimal. Women physicians had lower ASCVD burden, scored higher in healthy factors, but, took part in less physical activity than the non-physician cohort. These results call for population-specific early and improved risk intervention.

Assessment of cardiac output and volume load by transpulmonary thermodilution technique in immature pigs.

OBJECTIVE: To assess the accuracy of cardiac output (CO) measured by transpulmonary thermodilution technique (TPTD)and explore the validity of intrathoracic blood volume index (ITBVI) for assessment of circulatory volume status. METHODS: Ten immature pigs with a mean weight of (20.6±1.9)kg were studied during the conditions including normovolemia, hypervolemia, and hypovolemia. Simultaneous CO was measured in each condition using pulmonary artery thermodilution (PATD) method and TPTD. More specifically, CO (COPA) was determined with PATD, while CO (COTP) and ITBVI were determined with TPTD. All measurements were repeated 3 times. Central venous pressure (CVP) and heart rate were measured at the same time. The potential correlations of CVP and ITBVI with cardiac index (CI) and stroke volume index (SVI) in each blood volume status were analyzed. RESULTS: A total of 90 simultaneous measurements of COPA and COTP in 3 different blood volume conditions were made. The correlation coefficient between the two measurements was 0.977 (P<0.001) and the mean difference was (0.25±0.26)L/min (95%CI:0.20-0.30 L/min, P<0.001). The coefficient of variation of COTP was 3.7%, while COPA was 5.4%. Compared with those in normovolemia, CVP and ITBVI in hypervolemia significantly increased (P=0.002, 0.019), ITBVI in hypovolemia decreased significantly (P<0.001), and CVP in hypovolemia decreased insignificantly (P=0.05). Correlation analysis revealed a significant correlation between ITBVI with CI and SVI in normovolemia (r=0.741, P=0.014; r=0.885, P=0.001). In contrast, correlations between CVP with CI and SVI were poor. CONCLUSIONS: TPTD can accurately and precisely measure CO in different blood volume conditions. ITBVI measured by TPTD has better validity for the assessment of circulatory volume status than CVP.

MS/MS-based molecular networking discovery of sesquiterpenes from Carpesium abrotanoides L. with their cytotoxic and acetylcholinesterase inhibitory activity.

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation.

The impact of female sex hormones on cardiovascular disease: from mechanisms to hormone therapy.

Cardiovascular disease remains the leading cause of mortality in women, yet it has not raised the awareness from the public. The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones. Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects. Before menopause, cardiovascular protective effects of estrogens have been well described. Progestogens were often used in combination with estrogens in hormone therapy. Fluctuations in sex hormone levels, particularly estrogen deficiency, were considered the specific risk factor in women's cardiovascular disease. However, considerable heterogeneity in the impact of hormone therapy was observed in clinical trials. The heterogeneity is likely closely associated with factors such as the initial time, administration route, dosage, and formulation of hormone therapy. This review will delve into the pathogenesis and hormone therapy, summarizing the effect of female sex hormones on hypertension, pre-eclampsia, coronary heart disease, heart failure with preserved ejection fraction, and cardiovascular risk factors specific to women.

Drug-eluting stents versus bare-metal stents in patients with decreased GFR: a meta-analysis.

BACKGROUND: Decreased estimated glomerular filtration rate (eGFR) is a strong predictor of both mortality and subsequent cardiac events after percutaneous coronary intervention. The safety and efficacy of drug-eluting (DESs) versus bare-metal stents (BMSs) in this population have not been evaluated adequately. STUDY DESIGN: A systematic review and meta-analysis. SETTING & POPULATION: Studies involving the comparison of clinical outcomes between DESs and BMSs in patients with eGFR <60 mL/min/1.73 m(2). Studies exclusively involving patients with ST-segment elevation myocardial infarction were excluded. SELECTION CRITERIA FOR STUDIES: MEDLINE (on Ovid), EMBASE, and the Cochrane Library databases from 2002-2013 were searched for studies comparing DESs with BMSs in patients with eGFR <60 mL/min/1.73 m(2). INTERVENTION: DES versus BMS implantation. OUTCOMES: Mortality, repeat revascularization, myocardial infarction, and stent thrombosis. RESULTS: Data from 26 comparative studies with 66,840 patients were included. Compared with BMSs, DESs were associated with significant reductions in repeat revascularization (OR, 0.61; 95% CI, 0.50-0.74; P < 0.001) and myocardial infarction (OR, 0.85; 95% CI, 0.79-0.92; P < 0.001), with no detectable difference in stent thrombosis (OR, 0.72; 95% CI, 0.46-1.12; P = 0.1). The superiority of DESs over BMSs in decreasing mortality also was documented (OR, 0.77; 95% CI, 0.65-0.90; P = 0.01). This survival benefit of DESs over BMSs was attenuated in randomized controlled trials or adjusted observational studies versus unadjusted observational studies. LIMITATIONS: Most studies were observational studies. Meta-analysis was not performed on individual patient data. CONCLUSIONS: DES use in patients with eGFR <60 mL/min/1.73 m(2) is associated with a reduced rate of repeat revascularization and myocardial infarction without increased risk of stent thrombosis. The true effect of DESs versus BMSs on mortality needs to be confirmed by randomized controlled trials.

[Effects of allitridi capsules on endothelial function and clinical prognosis after percutaneous coronary intervention in coronary artery disease patients with diabetes mellitus].

OBJECTIVE: To explore the effects of allitridi capsules on endothelial function and clinical prognosis after percutaneous coronary intervention (PCI) in coronary artery disease (CAD) patients with diabetes mellitus (DM). METHODS: A total of 120 CAD patients with DM undergoing PCI were randomly assigned to receive conventional (control, n = 60) and additional allitridi treatment (120 mg/day, n = 60) for 3 months.Serum nitric oxide (NO) and intercellular adhesion molecule 1 (ICAM-1) levels were determined by enzyme-linked immunosorbent assay (ELISA) immediately and at 3 months post-PCI. Endothelial function was assessed by endothelium dependent flow-mediated dilation (FMD). Duration of follow-up was 1 year after PCI. RESULTS: The clinical characteristics, serum NO and ICAM-1 levels and FMD at baseline were not different between two groups. At Month 3 post-PCI, serum NO level was markedly higher ((147 ± 32) vs (112 ± 24) µmol/L, P = 0.009) and serum ICAM-1 level was significantly lower ((182 ± 21) vs (232 ± 29) µmol/L, P = 0.021) in the allitridi group than in the control group.Furthermore, treatment of allitridi resulted in a significant improvement of FMD (8.2% ± 2.4% vs 6.4% ± 2.3%, P = 0.013). At Year 1 post-PCI, the incidence of major adverse cardiovascular event (MACE) was lower in the allitridi group than that in the control group (10.5% vs 17.2%, P = 0.022). CONCLUSIONS: Allitridi capsules significantly improve the clinical prognosis after PCI in CAD patients with DM. Its mechanism may lies in improved endothelial function and vascular inflammatory state.

Efficacy and safety of riociguat replacing PDE-5is for patients with pulmonary arterial hypertension: A systematic review and meta-analysis.

Introduction: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Some patients treated with phosphodiesterase type 5 inhibitors (PDE-5is) fail to reach treatment goals. As a novel soluble guanylate cyclase agonist, riociguat acts on the same pathway as PDE-5is but functions via different mechanisms. Whether riociguat is more effective and safer than PDE-5is is ambiguous. We aimed to evaluate the efficacy and safety of switching from PDE-5is to riociguat among these patients. Methods: Original published articles were retrieved from PubMed/Medline, Embase, Web of Science, Open Grey and Google Scholar. Studies that assessed the World Health Organization functional class (WHO-FC), 6-min walking distance (6MWD), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), cardiac index (CI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were collected. Adverse events after switching were evaluated. Results: Ten published studies were included. Compared to PDE-5is, riociguat significantly increased the 6MWD by 26.45 m weighted mean difference (WMD) = 26.45 m, 95% confidence intervals (CIs): 9.70-43.2 m, p = 0.002) and improved mPAP (WMD = -3.53, 95% CIs: -5.62-1.44 mmHg, p = 0.0009), PVR (WMD = -130.24 dyn·s·cm-5, 95% CI -187.43-73.05, p < 0.0001), CIs (WMD = 0.36 L/min·cm-2, 95% CIs: 0.25-0.47, p < 0.00001) and WHO-FC (OR = 0.11, 95% CIs: 0.08-0.16, p < 0.0001) but not NT-proBNP. In addition, we did not observe the most common side effects during the replacement of riociguat for PDE-5is. Conclusions: PAH patients benefit from PDE-5is compared to riociguat, including in hemodynamic parameters, 6MWD, WHO-FC and biomarkers.

Association of pre-diagnosis specific color groups of fruit and vegetable intake with ovarian cancer survival: results from the ovarian cancer follow-up study (OOPS).

Background: The colors of fruits and vegetables (FV) reflect the presence of pigmented bioactive compounds. The evidence of pre-diagnosis specific FV color group intake contributing to ovarian cancer (OC) survival is limited and inconsistent. Methods: A prospective cohort study was conducted between 2015 and 2020 with 700 newly diagnosed OC patients. Pre-diagnosis dietary information was assessed by a validated food frequency questionnaire. We classified FV into five groups based on the color of their edible parts (e.g., green, red/purple, orange/yellow, white, and uncategorized groups). Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of specific color groups of FV before diagnosis with OC survival. Potential multiplicative and additive interactions were assessed. Results: 130 patients died during a median follow-up of 37.57 (interquartile: 24.77-50.20) months. We observed the improved survival with a higher pre-diagnosis intake of total FV (HRtertile 3 vs. tertile 1 = 0.63, 95%CI = 0.40-0.99), total vegetables (HRtertile 3 vs. tertile 1 = 0.57, 95%CI = 0.36-0.90), and red/purple FV (HRtertile 3 vs. tertile 1 = 0.52, 95%CI = 0.33-0.82). In addition, we observed significant dose-response relationships for per standard deviation increment between total vegetable intake (HR = 0.79, 95%CI = 0.65-0.96) and red/purple group intake (HR = 0.77, 95%CI = 0.60-0.99) before diagnosis with OC survival. Additionally, pre-diagnosis green FV intake was borderline associated with better OC survival (HRper standard deviation increment = 0.83; 95%CI = 0.69-1.00). In contrast, we did not observe significant associations between pre-diagnosis intake of total fruits, orange/yellow, white, and uncategorized groups and OC survival. Conclusion: Pre-diagnosis FV intake from various color groups, especially the green and red/purple ones, may improve OC survival. Further studies are needed to validate our findings.

Corrigendum: Efficacy and safety of riociguat replacing PDE-5is for patients with pulmonary arterial hypertension: A systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphar.2023.1052546.].