Baduanjin for ischemic heart failure with mildly reduced/preserved ejection fraction (BEAR Trial): A randomized controlled trial.

AIM: While Baduanjin, a traditional Chinese mind-body exercise, has shown potential health benefits, its efficacy in improving outcomes for heart failure patients with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) has not been well documented. We aimed to investigate the adjunctive impact of Baduanjin on exercise capacity and quality of life for HFmrEF/HFpEF. METHODS: Patients with HFmrEF/HFpEF were enrolled in this multicenter randomized clinical trial. All participants were randomized to conventional cardiac rehabilitation with or without an additional 12-week Baduanjin exercise. The primary endpoint was the distance covered in a 6-min walk test (6MWD), while key secondary outcomes included quality of life measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and cardiopulmonary function including anaerobic threshold (VO2 AT). RESULTS: A total of 120 patients were enrolled, and 109 completed all session and tests. The mean age of the 120 patients was 60.5 years (SD, 9.21 years), and 23 (19.2%) were women. The Baduanjin group exhibited a 6.14% improvement in 6MWD compared to a 1.32% improvement in the control group (median improvement, 25.0 vs. 5.0 m; p < 0.001) at 12th week. The VO2 AT increased by 25.87% in the Baduanjin group versus 3.94% in the control group (p < 0.001). Quality of life also significantly improved in the Baduanjin group as indicated by MLHFQ score changes (-16.8% vs. -3.99%; p < 0.001). CONCLUSIONS: Adding Baduanjin to exercise-based cardiac rehabilitation for patients with ischemic HFmrEF or HFpEF are generally safe and could provide significant improvements in exercise capacity and quality of life.

Redox-Active Ferrocene Quencher-Based Supramolecular Nanomedicine for NIR-II Fluorescence-Monitored Chemodynamic Therapy.

Real-time monitoring of hydroxyl radical (⋅OH) generation is crucial for both the efficacy and safety of chemodynamic therapy (CDT). Although ⋅OH probe-integrated CDT agents can track ⋅OH production by themselves, they often require complicated synthetic procedures and suffer from self-consumption of ⋅OH. Here, we report the facile fabrication of a self-monitored chemodynamic agent (denoted as Fc-CD-AuNCs) by incorporating ferrocene (Fc) into ß-cyclodextrin (CD)-functionalized gold nanoclusters (AuNCs) via host-guest molecular recognition. The water-soluble CD served not only as a capping agent to protect AuNCs but also as a macrocyclic host to encapsulate and solubilize hydrophobic Fc guest with high Fenton reactivity for in vivo CDT applications. Importantly, the encapsulated Fc inside CD possessed strong electron-donating ability to effectively quench the second near-infrared (NIR-II) fluorescence of AuNCs through photoinduced electron transfer. After internalization of Fc-CD-AuNCs by cancer cells, Fenton reaction between redox-active Fc quencher and endogenous hydrogen peroxide (H2 O2 ) caused Fc oxidation and subsequent NIR-II fluorescence recovery, which was accompanied by the formation of cytotoxic ⋅OH and therefore allowed Fc-CD-AuNCs to in situ self-report ⋅OH generation without undesired ⋅OH consumption. Such a NIR-II fluorescence-monitored CDT enabled the use of renal-clearable Fc-CD-AuNCs for efficient tumor growth inhibition with minimal side effects in vivo.

Iron-siRNA Nanohybrids for Enhanced Chemodynamic Therapy via Ferritin Heavy Chain Downregulation.

Ferrous iron (Fe2+ ) has more potent hydroxyl radical (⋅OH)-generating ability than other Fenton-type metal ions, making Fe-based nanomaterials attractive for chemodynamic therapy (CDT). However, because Fe2+ can be converted by ferritin heavy chain (FHC) to nontoxic ferric form and then sequestered in ferritin, therapeutic outcomes of Fe-mediated CDT agents are still far from satisfactory. Here we report the synthesis of siRNA-embedded Fe0 nanoparticles (Fe0 -siRNA NPs) for self-reinforcing CDT via FHC downregulation. Upon internalization by cancer cells, pH-responsive Fe0 -siRNA NPs are degraded to release Fe2+ and FHC siRNA in acidic endo/lysosomes with the aid of oxygen (O2 ). The accompanied O2 depletion causes an intracellular pH decrease, which further promotes the degradation of Fe0 -siRNA NPs. In addition to initiating chemodynamic process, Fe2+ -catalyzed ⋅OH generation facilitates endo/lysosomal escape of siRNA by disrupting the membranes, enabling FHC downregulation-enhanced CDT.

Enhancing Catalytic Activity of a Nickel Single Atom Enzyme by Polynary Heteroatom Doping for Ferroptosis-Based Tumor Therapy.

As a rising generation of nanozymes, single atom enzymes show significant promise for cancer therapy, due to their maximum atom utilization efficiency and well-defined electronic structures. However, it remains a tremendous challenge to precisely produce a heteroatom-doped single atom enzyme with an expected coordination environment. Herein, we develop an anion exchange strategy for precisely controlled production of an edge-rich sulfur (S)- and nitrogen (N)-decorated nickel single atom enzyme (S-N/Ni PSAE). In particular, sulfurized S-N/Ni PSAE exhibits stronger peroxidase-like and glutathione oxidase-like activities than the nitrogen-monodoped nickel single atom enzyme, which is attributed to the vacancies and defective sites of sulfurized nitrogen atoms. Moreover, both in vitro and in vivo results demonstrate that, compared with nitrogen-monodoped N/Ni PSAE, sulfurized S-N/Ni PSAE more effectively triggers ferroptosis of tumor cells via inactivating glutathione peroxidase 4 and inducing lipid peroxidation. This study highlights the enhanced catalytic efficacy of a polynary heteroatom-doped single atom enzyme for ferroptosis-based cancer therapy.

Amplification of Lipid Peroxidation by Regulating Cell Membrane Unsaturation To Enhance Chemodynamic Therapy.

Lipid peroxidation (LPO) is one of the most damaging processes in chemodynamic therapy (CDT). Although it is well known that polyunsaturated fatty acids (PUFAs) are much more susceptible than saturated or monounsaturated ones to LPO, there is no study exploring the effect of cell membrane unsaturation degree on CDT. Here, we report a self-reinforcing CDT agent (denoted as OA@Fe-SAC@EM NPs), consisting of oleanolic acid (OA)-loaded iron single-atom catalyst (Fe-SAC)-embedded hollow carbon nanospheres encapsulated by an erythrocyte membrane (EM), which promotes LPO to improve chemodynamic efficacy via modulating the degree of membrane unsaturation. Upon uptake of OA@Fe-SAC@EM NPs by cancer cells, Fe-SAC-catalyzed conversion of endogenous hydrogen peroxide into hydroxyl radicals, in addition to initiating the chemodynamic therapeutic process, causes the dissociation of the EM shell and the ensuing release of OA that can enrich cellular membranes with PUFAs, enabling LPO amplification-enhanced CDT.

Effects of different rehabilitation modality on cardiopulmonary function in patients with acute coronary syndrome after revascularization.

Objective: To investigate the effects of different rehabilitation modalities on cardiopulmonary function in patients with acute coronary syndrome after revascularization. Methods: Two randomized controlled trials were conducted. All patients were stable for more than 48 h and less than 1 week after revascularization for acute coronary syndrome and were randomly assigned to Group A (home-based rehabilitation group) or Group B (center guided home-based rehabilitation group). The cardiopulmonary exercise test was mainly performed before and 3 months after cardiac rehabilitation (at the end of intervention). The primary endpoints of the study were peak oxygen uptake (VO2peak), and the secondary endpoints were maximum metabolic equivalents (METs), anaerobic threshold exercise load (Load AT), maximal workload (Load max), and anaerobic threshold oxygen uptake (VO2 AT). Results: A total of 106 patients were included in the study, with 47 patients in Group A (with 6 losses) and 50 patients in Group B (with 3 losses). There were no significant difference between the two groups in terms of age, gender, body mass index (BMI), left ventricular ejection fraction(LVEF), low-density lipoprotein cholesterol(LDL-C),cardiovascular risk factors. In Group A, no significant differences in CPET indices were observed before and after the intervention. In Group B, values of maximum metabolic equivalents (METs), peak heart rate (PHR), anaerobic threshold exercise load (Load AT), maximal workload (Load max), maximum ventilation per minute (VE max), peak oxygen uptake (VO2peak), anaerobic threshold oxygen uptake (VO2 AT) and maximum oxygen pulse (VO2/HRmax) were higher than those before the intervention (P < 0.05). In addition, METs (max), Load AT, Load max, VO2 AT, and VO2peak in Group B were higher than those in group A (P < 0.05). The change rates of VO2peak, METs(max), PHR, Load max, VO2 AT, VE max, VO2/HR(max) in the two groups were significantly different before and after intervention (P < 0.05). Conclusion: Cardiac exercise rehabilitation is helpful for improving patients' cardiopulmonary endurance and quality of life. Moreover, rehabilitation modalities with regular hospital guidance can improve cardiopulmonary function in a shorter period,which seems to be more effective than a complete home-based rehabilitation model. Clinical Trial Registration: http://www.chictr.org.cn, identifier (ChiCTR2400081034).

Biological evaluation of a novel bilirubin adsorbent and its therapeutic effect on animal models of hyperbilirubinemia.

Hyperbilirubinemia caused severe hepatobiliary diseases with various causes, especially hepatic fibrosis and cirrhosis caused by end-stage hepatitis B and C. Plasma adsorption perfusion (PP) has a tremendous advantage in treating patients with hyperbilirubinemia and liver failure, wherein, a safe and effective adsorbent is the key to filter out bilirubin successfully in PP. In this work, a simple engineering strategy, a new porous polymer adsorption resin ERM-0100 based on the homopolymer predispersion system, is proposed to produce high-performance bilirubin adsorbents. Preliminary experimental results show that ERM-0100 exhibits a large surface area and uniformly porous structure. Experimental results verify that ERM-0100 has high biocompatibility and bilirubin adsorption efficiency (TBIL:35%, direct bilirubin [DBIL]:30%, IBIL:87%) that is significantly higher than most of the reported adsorbents. Animal experiments prove that ERM-0100 has high bilirubin adsorption efficiency and can improve the liver function of animals. The combination of high biocompatibility and high adsorption capacity positions the ERM-0100 as a promising candidate for bilirubin removal.

Efficacy and Safety of Resistance Training for Coronary Heart Disease Rehabilitation: A Systematic Review of Randomized Controlled Trials.

Background: Resistance training (RT), as part of exercise prescriptions during cardiac rehabilitation for patients with cardiovascular disease (CVD), is often used as a supplement to aerobic training (AT). The effectiveness and safety of RT has not been sufficiently confirmed for coronary heart disease (CHD). Objective: To provide updated evidence from randomized clinical trials (RCTs) on efficacy and safety of RT for the rehabilitation of CHD. Method: Three English and four Chinese electronic literature databases were searched comprehensively from establishment of each individual database to Dec, 2020. RCTs which compared RT with AT, no treatment, health education, physical therapy, conventional medical treatment (or called usually care, UC) in CHD were included. Methodological quality of RCTs extracted according to the risk of bias tool described in the Cochrane handbook. The primary outcomes were the index of cardiopulmonary exercise testing and the quality of life (QOL). The secondary outcomes included the skeletal muscle strength, aerobic capacity, left ventricular function and structure. Results: Thirty-right RCTs with a total of 2,465 participants were included in the review. The pooling results suggest the RT+AT is more effective in the cardiopulmonary exercise function (peak oxygen uptake, peak VO2) [MD, 1.36; 95% CI, 0.40-2.31, P = 0.005; I 2 = 81%, P < 0.00001], the physical score of QOL [SMD, 0.71; 95% CI, 0.33-1.08, P = 0.0003; I 2 = 74%, P < 0.0001] and global score of QOL [SMD, 0.78; 95% CI, 0.43-1.14, P < 0.0001; I 2 = 60%, P = 0.03], also in the skeletal muscle strength, the aerobic capacity and the left ventricular ejection fraction (LVEF) than AT group. However, there is insufficient evidence confirmed that RT+AT can improve the emotional score of QOL [SMD, 0.27; 95% CI, -0.08 to 0.61, P = 0.13; I 2 = 70%, P = 0.0004] and decrease left ventricular end-diastolic dimension (LVEDD). No significant difference between RT and AT on increasing peak VO2 [MD, 2.07; 95% CI, -1.96 to 6.09, P = 0.31; I 2 = 97%, P < 0.00001], the physical [SMD, 0.18; 95% CI, -0.08 to 0.43, P = 0.18; I 2 = 0%, P = 0.51] and emotional [SMD, 0.22; 95% CI, -0.15 to 0.59, P = 0.24; I 2 = 26%, P = 0.25] score of QOL. Moreover, the pooled data of results suggest that RT is more beneficial in increasing peak VO2 [MD, 3.10; 95% CI, 2.52-3.68, P < 0.00001], physical component [SMD, 0.85; 95% CI, 0.57-1.14, P < 0.00001; I 2 = 0%, P = 0.64] and the emotional conditions [SMD, 0.74; 95% CI, 0.31-1.18, P = 0.0009; I 2 = 58%, P = 0.12] of QOL and LVEF, and decreasing LVEDD than UC. Low quality evidence provided that RT had effect in decreasing rehospitalization events than UC [RR, 0.33, 95% CI 0.17 to 0.62, P = 0.0006; I 2 = 0%, P = 0.64]. There is no significant difference in the safety of RT compared to AT. Conclusions: RT combined with AT is more beneficial than AT alone for CHD. RT can effectively improve the capacity of exercise and the QOL compared with UC. But the difference between RT and AT is still unknown. More high-quality and large-sample studies are needed to confirm our findings.

A One-pot-synthesized Double-layered Anticoagulant Hydrogel Tube.

Extracorporeal membrane oxygenation(ECMO) has emerged as a viable treatment in severe cases of acute respiratory distress syndrome, acute respiratory failure, and adult respiratory distress syndrome. However, thromboembolic events stemming from the use of ECMO devices results in significant morbidity and mortality rates; the inner surface of the ECMO tubing comes into contact with the blood and can readily initiate coagulation. In addition, the tubing needs to be continually replaced due to thromboses on the inner tube wall, which not only increases the risk of infection but also the economic burden. Despite considerable effort, a surface modification strategy that effectively addresses these challenges has not yet been realized. In this study, we developed an integrated hollow core-shell-shell hydrogel tube of gelatin/alginate/acrylamide-bacterial nanocellulose(GAA) that meets the anticoagulant requirements for the inner tubing layer as well as the highly elastic soft material needed for the outer layer. Using static blood from healthy volunteers, we confirmed that the platelets or coagulation is not stimulated by the GAA tubing. Importantly, experiments with dynamic blood also demonstrated that the inner layer of the tubing does not elicit blood clotting. The one-pot-synthesized process may provide guidance for the design of anticoagulation tubes used clinically. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at 10.1007/s40242-021-1267-3.

Exosomes derived from bone marrow mesenchymal stem cells reverse epithelial-mesenchymal transition potentially via attenuating Wnt/ß-catenin signaling to alleviate silica-induced pulmonary fibrosis.

Pulmonary fibrosis induced by silica dust is an irreversible, chronic, and fibroproliferative lung disease with no effective treatment at present. BMSCs-derived exosomes (BMSCs-Exo) possess similar functions to their parent cells. In this study, we investigated the therapeutic potential and underlying molecular mechanism for BMSCs-Exo in the treatment of silica-induced pulmonary fibrosis. The rat model of experimental silicosis pulmonary fibrosis was induced with 1.0 mL of one-off infusing silica suspension using the non-exposed intratracheal instillation (50 mg/mL/rat). In vivo transplantation of BMSCs-Exo effectively alleviated silica-induced pulmonary fibrosis, including a reduction in collagen accumulation, inhibition of TGF-ß1, and decreased HYP content. Treatment of BMSCs-Exo increased the expression of epithelial marker proteins including E-cadherin (E-cad) and cytokeratin19 (CK19) and reduced the expression of fibrosis marker proteins including α-Smooth muscle actin (α-SMA) after exposure to silica suspension. Furthermore, we found that BMSCs-Exo inhibited the expression of Wnt/ß-catenin pathway components (P-GSK3ß, ß-catenin, Cyclin D1) in pulmonary fibrosis tissue. BMSCs-Exo is involved in the alleviation of silica-induced pulmonary fibrosis by reducing the level of profibrotic factor TGF-ß1 and inhibiting the progression of epithelial-mesenchymal transition (EMT). Additionally, attenuation of the Wnt/ß-catenin signaling pathway closely related to EMT may be one of the mechanisms involved in anti-fibrotic effects of exosomes.

Sodium Tanshinone II A Sulfonate for Coronary Heart Disease: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: To assess whether an adjunctive therapy of Sodium Tanshinone II A Sulfonate Injection (STS) is effective and safe in improving clinical outcomes in patients with coronary heart disease (CHD). METHODS: A literature search was conducted through PubMed, the Cochrane Library, Knowledge Infrastructure Databases (CNKI), Chinese Biomedical Literature Database (SinoMed), Chinese Science and Technology Periodical Database (VIP) and Wanfang Database up to August 2017. Randomized controlled trials (RCTs) comparing STS with placebo or no additional treatments on the basis of standard conventional medicine therapies were included. The outcomes were all-cause mortality, major acute cardiovascular events (MACEs), cardiac function and inflammatory factors. The risk of bias assessment according to the Cochrane Handbook was used to evaluate the methodological quality of the included trials. Revman 5.3 software was used for data analyses. RESULTS: A total of 22 RCTs involving 1,873 participants were included. All of the trials used STS as adjunctive treatment to standard conventional medicine therapy. Due to the poor quality of methodologies of most trials, only limited evidence showed that a combination of STS with percutaneous coronary intervention (PCI) or thrombolytic therapy (TT) might be more effective on reduction of all cause death rate than TT alone [risk ratio (RR) 0.25, 95% confidence interval (CI) 0.07 to 0.87] or PCI alone (RR 0.42, 95% CI 0.04 to 4.36). The results of 6 trials comparing STS plus TT with TT alone showed that the addition of STS significantly reduced the incidence of cardiac shock (RR 0.35, 95% CI 0.14 to 0.86), heart failure (RR 0.41, 95% CI 0.20 to 0.83) and arrhythmia (RR 0.21, 95% CI 0.12 to 0.46). STS combined with TT also showed a superior effect on cardiac function and inflammatory factor. No severe adverse event was reported related to STS. CONCLUSIONS: As an adjunctive therapy, STS combined with standard conventional medicine seems to be more effective on all-cause mortality or MACEs than conventional medicine treatment alone with less side effects. However, we cannot make a firm conclusion due to low quality of inclusion trials. Well-designed trials with high methodological quality are needed to validate the effect of STS for CHD patients.

Tanshinone IIA Exerts Anti-Inflammatory and Immune-Regulating Effects on Vulnerable Atherosclerotic Plaque Partially via the TLR4/MyD88/NF-κB Signal Pathway.

Background: Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA's anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in ApoE-deficient (ApoE-/-) mice. Methods: Male ApoE-/- mice (6 weeks) were fed with a high-fat diet for 13 weeks and then randomized to the model group (MOD) or Tan IIA groups [high dose: 90 mg/kg/day (HT), moderate dose: 30 mg/kg/day (MT), low dose: 10 mg/kg/day (LT)] or the atorvastatin group (5 mg/kg/day, ATO) for 13 weeks. Male C57BL/6 mice (6 weeks) were fed with ordinary rodent chow as control. The plaque stability was evaluated according to the morphology and composition of aortic atherosclerotic (AS) plaque in H&E staining and Movat staining sections by calculating the area of extracellular lipid, collagenous fiber, and foam cells to the plaque. The expression of the Toll-like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear factor-kappa B (NF-κB) signal pathway in aorta fractions was determined by immunohistochemistry. Serum levels of blood lipid were measured by turbidimetric inhibition immunoassay. The concentrations of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by cytometric bead array. Results: Tan IIA stabilized aortic plaque with a striking reduction in the area of extracellular lipid (ATO: 13.15 ± 1.2%, HT: 12.2 ± 1.64%, MT: 13.93 ± 1.59%, MOD: 18.84 ± 1.46%, P < 0.05) or foam cells (ATO: 16.05 ± 1.26%, HT: 14.88 ± 1.79%, MT: 16.61 ± 1.47%, MOD: 22.08 ± 1.69%, P < 0.05) to the plaque, and an evident increase in content of collagenous fiber (ATO: 16.22 ± 1.91%, HT: 17.58 ± 1.33%, MT: 15.71 ± 2.26%, LT:14.92 ± 1.65%, MOD: 9.61 ± 0.7%, P < 0.05) to the plaque than that in the model group, concomitant with down-regulation of the protein expression of TLR4, MyD88, and NF-κB p65, and serum level of MCP-1 and TNF-α in a dose-dependent manner. There were no differences in serum TC, LDL, HDL, or TG levels between ApoE-/- mice and those treated with atorvastatin. Conclusions: These results suggest that Tan IIA could stabilize vulnerable AS plaque in ApoE-/- mice, and this anti-inflammatory and immune-regulating effect may be achieved via the TLR4/MyD88/NF-κB signaling pathway.

Acupuncture for Primary Insomnia: An Updated Systematic Review of Randomized Controlled Trials.

Introduction: Acupuncture as one of the alternative therapies for insomnia is widely used in Asia and increasingly employed in western countries. Objectives: To provide updated evidence from randomized controlled trials (RCTs) on the effectiveness and safety of acupuncture for primary insomnia. Methods: A comprehensive literature search in 11 databases was conducted from January 2008 to October 2017. Two authors independently extracted data and assessed risk of bias independently. Statistical analysis was performed using RevMan 5.3 software. According to predefined protocol, we combined data in meta-analysis and performed trial sequential analysis when appropriate. Grading of Recommendations Assessment, Development, and Evaluation was also conducted to assess the quality of evidence. Results: A total of 73 RCTs involving 5533 participants were analyzed. The pooled results showed better effect from real acupuncture than no treatment (mean difference [MD] -5.58, 95% confidence interval [CI] -6.85 to -4.31, I2 = 0%, p < 0.00001, 2 trials, fixed effect model, 105 participants) on reducing Pittsburgh Sleep Quality Index (PSQI) scores with "very low quality" evidence. Acupuncture plus drugs showed better improvement than drugs alone on decreasing the PSQI total scores (MD -3.17, 95% CI -4.74 to -1.61, I2 = 72%, 4 trials, random-effects model (REM), p < 0.0001, 253 participants, low quality). Similar benefit favored acupuncture compared with no treatment (MD -8.46, 95% CI -9.59 to -7.33, I2 = 0%, p < 0.00001, 2 trials, 65 participants). Acupuncture showed more benefit than estazolam on PSQI (with enough statistical power). Athens Insomnia Scale (MD -1.64, 95% CI -2.40 to -0.89, I2 = 0%, p < 0.0001, 3 trials, fixed-effects model, 180 participants) or SPIEGEL (MD -2.86, 95% CI -3.54 to -2.18, p < 0.00001, I2 = 0%, 5 trials, fixed-effects model, 326 participants) with "very low-quality" evidence. Furthermore, low-quality evidence showed less adverse events from acupuncture than western medications (risk ratio 0.23, 95% CI 0.11-0.48, I2 = 56%, p < 0.0001, 11 trials, REM, 914 participants). Publication bias was likely present based on the PSQI total scores. Conclusions: The summary estimates indicate that acupuncture might result in improvement than no treatment on PSQI scores and appears safe. However, the quality of the evidence is varied from very low to low due to the potential risk of bias and inconsistency among included trials. Further large sample size and rigorously designed RCTs are still needed.

Baduanjin exercise for patients with ischemic heart failure on phase-II cardiac rehabilitation (BEAR trial): study protocol for a prospective randomized controlled trial.

BACKGROUND: Preliminary evidence based on clinical observations suggests that meditative exercise may offer potential benefits for patients with chronic heart failure (CHF). Cardiac rehabilitation (CR), as a class-IA indication in clinical practice guidelines, has been established as an effective strategy to improve quality of life and prognosis of CHF patients. Baduanjin exercise is an important component of traditional Chinese Qigong exercises. However, its benefits for CHF have not been rigorously tested. We sought to investigate whether Baduanjin, as an adjunct to standard care, improves cardiopulmonary function, exercise tolerance, and quality of life in patients with CHF caused by coronary artery disease (CAD). METHODS/DESIGN: In this randomized controlled trial, 120 patients will be randomly allocated in a 1:1 ratio to Baduanjin exercise combined with conventional exercise of CR (Baduanjin exercise group) or conventional exercise of CR alone (conventional exercise group). In addition to conventional physical activity, participants in the Baduanjin exercise group will participate in a 45-min Baduanjin exercise training session twice a week, for 12 weeks. The primary outcome is walking distance in the 6-min Walk Test (6MWT), and the secondary outcomes are peak oxygen uptake (VO2 peak), ventilatory anerobic threshold (VAT), The minute ventilation to carbon dioxide production relationship (VE/VCO2 slope), left ventricular end-diastolic volume index (LVEDVi), left ventricular ejection fraction (LVEF), quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), amino-terminal pro-brain natriuretic peptide (NT-proBNP), hs-CRP, heart rate variability (HRV), New York Heart Association (NYHA) classification, and major adverse cardiovascular events. DISCUSSION: This is the first trial to evaluate the effects of a Baduanjin exercise-based CR program on cardiopulmonary function and exercise tolerance in ischemic CHF patients. If successful, it will prove the value of Baduanjin exercise in improving cardiopulmonary function and exercise tolerance in patients with ischemic heart failure on phase-II CR, and may further develop a Chinese Qigong exercise-based CR framework. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03229681 . Registered retrospectively on 23 July 2017.

Preparation and Adsorption Properties of Novel Porous Microspheres with Different Concentrations of Bilirubin.

BACKGROUND: Plasma perfusion was widely used to clear toxic substances of plasma. Particle size and uniformity of adsorbent microspheres also affect the absorption rate. METHODS: Conventional suspension polymerization was improved using a pre-dispersion homogenizer to obtain novel adsorbent microspheres, named ERM-0100. Microsphere-related characteristics and attributes were analysed. RESULT: The ERM-0100 microspheres efficiently adsorbed different bilirubin concentrations, with a maximum rate of 59.72 ± 1.08%. At high bilirubin concentrations, ERM-0100 exhibited similar adsorption rate with BRS350 and BS330 (p = 0.303, p = 1.000, relatively), and higher than HB-H-6 (p = 0.000). At different concentration, ERM-0100 showed good adsorption performance. The ERM-0100 had no significant adsorption for electrolyte; for TP and ALB, the loss rates of ERM-0100 were 15.65 ± 0.36 and 23.23 ± 1.11%, respectively. In addition, ERM-0100 showed good blood compatibility. CONCLUSION: The ERM-0100 is a potential biomedical material for plasma perfusion for good effect, less costs and more safety. The microspheres may be coated to reduce its protein adsorption.

Preparation of sustained-release composite coating formed by dexamethasone and oxidated sodium alginate.

Inflammatory reaction and thrombosis are the unsolved main problems of non-coated biomaterials applied in cardiac surgery. In the present study, a series of sustained composite coating was prepared and characterized, such as in the chemical modification of polyvinyl chloride (PVC) for applications in cardiac surgery and the assessment of the biological property of modified PVC. The composite coatings were mainly formed by dexamethasone (DXM) and oxidated sodium alginate (OSA) through ionic and covalent bond methods. The biocompatibility and hemocompatibility of the coating surface were evaluated. Scanning electron microscopy analysis of the surface morphologies of the thrombus and platelets revealed that DXM-OSA coating improved the antithrombogenicity and biocompatibility of PVC circuits, which were essential for cardiac pulmonary bypass surgery. Evaluation of in vitro release revealed that the DXM on group PPC was gradually released in 8 h. Thus, DXM that covalently combined on the PVC surface showed sustained release. By contrast, DXM on groups PPI and PPD was quickly or shortly released, suggesting that groups PPI and PPD did not have sustained-release property. Overall, results indicated that the DXM-OSA composite coating may be a promising coating for the sustained delivery of DXM.

[Long-term anti-cancer implants inhibiting the activity of tumor growth in animal models].

This study was aimed to establish rat bladder tumor animal models to investigate the in viva antitumor effect of polyanhydride-pirarubicin (PAD-THP), a long-lasting anti-cancer implant, in the bladder tumor of animal models. The model of bladder cancer was set up with N-butly-N-(4 hydroxybutyl) nitrosamine (BBN) feeding into rats. The PAD-THP long-acting anti-cancer implants containing the drugs and the same dose of the THP naked drug were placed under the bladder mucosa of bladder tumor model in vivo. The pirarubicin plasma concentration was measured with high performance liquid chromatography (HPLC) detection in vivo. The effective drug concentration and lasting period were observed and compared in the animal bodies. The tumor sizes were measured before and after the treatment. The in viva antitumor effects were analyzed and compared. The results showed that more significant antitumor effect of PAD-THP implants on the local drug release characteristics were presented compared with that of the same dose of THP bare drug group and there were significant differences (P<0. 05) between the two methods. All the results indicated that the PAD-THP anti-cancer implants in the postoperative local treatment of bladder tumors would show prosperous in the future for clinical application.

Sodium alginate/heparin composites on PVC surfaces inhibit the thrombosis and platelet adhesion: applications in cardiac surgery.

Thrombosis and hemocyte damage are the main problems of applied non-coated biomaterials to cardiac surgery that remain unsolved. The present study is aimed at the chemical modification of polyvinyl chloride (PVC) for applications in cardiac surgery and the biological property assessment of modified PVC. Sodium alginate (SA)/heparin (HEP) composites were covalently immobilized onto the surface of the PVC pipeline. The surface grafting density and protein adsorption were determined by ultraviolet spectrophotometry. The surface contact angles were evaluated by contact-angle measurement, whereas the surface characteristics were evaluated by Fouriertransform infrared spectroscopy. Blood coagulation time and platelet adhesion were measured using an automated blood coagulation analyzer and a hemocytometer, respectively. Surface morphologies of the thrombus and platelets were evaluated by scanning electron microscopy. The immobilization of SA/HEP reduced the contact angles of the coated surface. Protein adsorption was reduced by the immobilization of SA. The activated partial thrombin time and thrombin time of the coated PVC were significantly prolonged as compared with the non-coated PVC. Platelet adhesion and thrombus formation were all reduced by the immobilization of HEP. The results revealed that the SA/HEP coating can improve the antithrombogenicity of the PVC pipeline, as well as improve its biocompatibility and hemocompatibility, which are essential for cardiac pulmonary bypass surgery.

Reconstruction of orbital defects by implantation of antigen-free bovine cancellous bone scaffold combined with bone marrow mesenchymal stem cells in rats.

BACKGROUND: Tissue-engineering approach can result in significant bone regeneration. We aimed to reconstruct the segmental orbital rim defects with antigen-free bovine cancellous bone (BCB) scaffolds combined with bone marrow mesenchymal stem cells (BMSCs) in rats. METHODS: BCB was prepared by degreasing, deproteinization and partly decalcification. BMSCs isolated from green fluorescent protein (GFP) transgenic rats were osteogenically induced and seeded onto BCB scaffolds to construct induced BMSCs/BCB composites. An 8-mm full-thickness defect on the rat inferior-orbit rim was established. Induced BMSCs/BCB composites cultured for 5 days were implanted into the orbital defects as the experimental group. Noninduced BMSCs/BCB group, BCB group and exclusive group were set. General condition, spiral CT, 3D orbital reconstruction, histological and histomorphometric analysis were performed after implantation. RESULTS: BCB presented reticular porous structure. GFP-BMSCs adhering to BCB appeared bright green fluorescence and grew vigorously. Infection and graft dislocation were not observed. In induced BMSCs/BCB group, CT and 3D reconstruction showed perfect orbital repair situation. Histological analysis indicated BCB was mostly biodegraded; newly formed bone and complete synostosis were observed. The percentage of newly formed bone was (57.12 ± 6.28) %. In contrast, more residual BCB, less newly formed bone and nonunion were observed in the noninduced BMSCs/BCB group. Slowly absorbed BCB enwrapped by fibrous connective tissue and a small amount of new bone occurred in BCB group. Fibrous connective tissue appeared in exclusive group. CONCLUSIONS: Antigen-free bovine cancellous bone that retains natural bone porous structure and moderate mechanical strength with elimination of antigen is the ideal carrier for mesenchymal stem cells in vitro. BCB combined with BMSCs is a promising composite for tissue engineering, and can effectively reconstruct the orbit rim defects in rats.

[The study of absorbable sustained-release implants and animal experiments to prevent recurrence of bladder cancer].

This paper aims to prepare polyanhydride-Pirarubicin dose long-acting sustained-release implants for the treatment of bladder cancer and for the prevention of postoperative recurrence of bladder cancer. Pirarubicin hydrochloride (THP) and polyanhydride, in accordance with a certain proportion, were fully mixed in the agate morta and dissolved in dichloromethane, and then were cast into a film within a mold put in the dryer set at 4 degrees C. Each tablet implanted contained 5.0 mg of THP. Polyanhydride-pirarubicin sustained-release was implanted into the bladder mucosa of the rabbits, and blood and urine samples were taken at different times after the operation. The THP drug concentrations in urine and blood were determined with high-performance liquid chromatography. The THP concentration in urine was significantly higher than the THP concentration in plasma. The drug concentration in urine reached (92.5 +/- 7.4) microg/L at 250 d time after the operation. Polyanhydride-pirarubicin implants possess long-acting sustained-release level dynamics in the body. It can maintain a stable long-term drug release and can be expected to last a year and can effectively prevent recurrence of bladder cancer. The present experiments proved that the implants with sustained-release drug treatment are expected to be useful in the clinical application in prevention of bladder cancer recurrence.