Objective
This study aimed to investigate the relationship between the duration of cardiopulmonary bypass (CPB) and stroke or early death in patients with acute type A aortic dissection (ATAAD) ...receiving total aortic arch replacement with the frozen elephant trunk procedure (TAR with FET).
Methods
A retrospective cohort study of 258 consecutive patients was conducted at Beijing Anzhen Hospital from December 2014 to June 2016. Patients who received TAR with FET for ATAAD were included. An adverse outcome (AO) was defined as 30-day mortality or stroke. Additionally, an AO was compared using propensity score matching.
Results
The incidence of AO was 13.6% (n = 35). The 30-day mortality rate was 10.8% and the stroke rate was 9.3%. Patients were aged 47.9 ± 10.6 years old. The duration of CPB was an independent predictor of occurrence of AO after adjusting for confounding factors by multivariable logistic regression analysis (odds ratio 1.101, 95% confidence interval 1.003–1.208). In matched analysis, CPB duration remained a risk factor of AO.
Conclusions
The duration of CPB is an independent predictor of AO in surgical repair for ATAAD. The underlying mechanisms of this association are important for developing improved prevention strategies.
Clinopodium chinense (Benth.) O. Ktze is a traditional Chinese herbal medicine, which comprises the plant's total flavonoids. TFCC plays an important role in the treatment of cardiovascular disease.
...The aim of the study was to study the protective effects and possible mechanism of TFCC against isoproterenol (ISO)-mediated myocardial injury in vivo and anoxia/reoxygenation (A/R)-induced H9c2 cell injury in vitro.
Male Sprague–Dawley (SD) rats were intragastrically pretreated with TFCC for 15 days. After 2 h of TFCC administration on days 14 and 15, a myocardial injury model was established with intragastric administration of 120 mg/kg of ISO daily for 2 days. The experiment was stopped 12 h after the last administration of the drugs. ECG recordings were taken after the treatment. Serum samples were assayed to determine the serum cardiac enzymes (e.g., creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). The left ventricle was excised for histopathological examination, and myocardial homogenates were prepared to detection catalase, glutathione peroxidase, and superoxide dismutase. Reactive oxygen species (ROS), heme oxygenase-1(HO-1),and peroxidase were detected by the corresponding ELISA kits. H9c2 cells were pretreated with different concentrations of TFCC for 12 h before A/R exposure. Afterward, cell viability, LDH release, hoechst 33,342, and peromide iodine (PI) double staining, JC-1 staining, and ROS examination were determined. Western blot analyses of B-cell lymphoma-2, Bcl-2associated X protein, cleaved cysteinylaspartate specific protease-3 and-9, nuclear factor 2(Nrf2), HO-1 and serine/threonine protein kinase (AKT), and P-AKT were conducted.
The pretreatment of TFCC (10, 20, and 40 mg/kg) daily for 15 days prevented ISO-induced myocardial damage, including the decrease in serum cardiac enzymes and cardiomyocyte apoptotic index and improvement in the heart rate and vacuolation. TFCC also improved the free radical scavenging and antioxidant potential, thereby suggesting that one possible mechanism of TFCC-induced cardio protection is mediated by blocking the oxidative stress. To clarify these mechanisms, we performed the in vitro study by A/R-induced cytotoxicity model in H9c2 cells. TFCC pretreatment prevented apoptosis, increased the expression of HO-1, and enhanced the nuclear translocation of Nrf2. TFCC also activated phosphorylation of AKT, whereas the addition of LY294002, which is the pharmacologic inhibitor of PI3K, blocked the TFCC-induced Nrf2/HO-1 activation and cytoprotective effect.
TFCC protects against myocardial injury and enhances cellular antioxidant defense capacity by inducing the phosphorylation of AKT, which subsequently activated the Nrf2/HO-1 signaling pathway.
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The optimal hypothermic level in total arch replacement with stented elephant trunk implantation for acute type A aortic dissection (aTAAD) has not been established, and the superiority of unilateral ...or bilateral cerebral perfusion remains a controversial issue. Therefore, we evaluated the application of moderate hypothermic circulatory arrest (MHCA) with a core temperature of 29 °C and bilateral selective antegrade cerebral perfusion in aTAAD treated by total arch replacement with stented elephant trunk implantation.
From July 2019 to January 2020, 25 aTAAD patients underwent total arch replacement with stented elephant trunk implantation via MHCA (29 °C) and bilateral selective antegrade cerebral perfusion (modified group). Thirty-six patients treated by the same procedure with MHCA (25 °C) and unilateral selective antegrade cerebral perfusion during this period were selected as controls.
There were no differences between the two groups of patients in terms of age, sex, incidence of hypertension, malperfusion, and pericardial effusion, although the incidence of cardiac tamponade was higher in the modified group (control 2.8%, modified 20%; P = 0.038). The lowest mean circulatory arrest temperature was 24.6 ± 0.9 °C in the control group, and 29 ± 0.8 °C in the modified group (P < 0.001). In-hospital mortality was 4.9% (3/61) for the entire cohort (control 8.3%, modified 0; P = 0.262). The incidence of permanent neurologic deficit was 4.9% (control 8.3%, modified 0; P = 0.262). There were no significant differences in the occurrence of temporary neurological deficit, renal failure, and paraplegia between groups. The rate of major adverse events in the modified group was lower (30.6% vs. 4%, P = 0.019). A shorter duration of ventilation and ICU stay was identified in the modified group, as well as a reduced volume of drainage within the first 48 h and red blood cell transfusion.
The early results of MHCA (29 °C) and bilateral selective antegrade cerebral perfusion applied in total arch replacement with stented elephant trunk implantation for aTAAD were acceptable, providing similar inferior cerebral and visceral protection compared with that of the conventional strategy. A higher core temperature may account for the shorter duration of ventilation and ICU stay, as well as a reduced volume of drainage and red blood cell transfusion.
Summary
Microglia‐mediated neuroinflammation plays a dual role in various brain diseases due to distinct microglial phenotypes, including deleterious M1 and neuroprotective M2. There is growing ...evidence that the peroxisome proliferator‐activated receptor γ (PPARγ) agonist rosiglitazone prevents lipopolysaccharide (LPS)‐induced microglial activation. Here, we observed that antagonizing PPARγ promoted LPS‐stimulated changes in polarization from the M1 to the M2 phenotype in primary microglia. PPARγ antagonist T0070907 increased the expression of M2 markers, including CD206, IL‐4, IGF‐1, TGF‐β1, TGF‐β2, TGF‐β3, G‐CSF, and GM‐CSF, and reduced the expression of M1 markers, such as CD86, Cox‐2, iNOS, IL‐1β, IL‐6, TNF‐α, IFN‐γ, and CCL2, thereby inhibiting NFκB–IKKβ activation. Moreover, antagonizing PPARγ promoted microglial autophagy, as indicated by the downregulation of P62 and the upregulation of Beclin1, Atg5, and LC3‐II/LC3‐I, thereby enhancing the formation of autophagosomes and their degradation by lysosomes in microglia. Furthermore, we found that an increase in LKB1–STRAD–MO25 complex formation enhances autophagy. The LKB1 inhibitor radicicol or knocking down LKB1 prevented autophagy improvement and the M1‐to‐M2 phenotype shift by T0070907. Simultaneously, we found that knocking down PPARγ in BV2 microglial cells also activated LKB1–AMPK signaling and inhibited NFκB–IKKβ activation, which are similar to the effects of antagonizing PPARγ. Taken together, our findings demonstrate that antagonizing PPARγ promotes the M1‐to‐M2 phenotypic shift in LPS‐induced microglia, which might be due to improved autophagy via the activation of the LKB1–AMPK signaling pathway.
The present study was designed to investigate whether Araloside C, one of the major triterpenoid compounds isolated from Aralia elata known to be cardioprotective, can improve heart function ...following ischaemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. We observed that Araloside C concentration‐dependently improved cardiac function and depressed oxidative stress induced by I/R. Similar protection was confirmed in isolated cardiomyocytes characterized by maintaining Ca2+ transients and cell shortening against I/R. Moreover, the potential targets of Araloside C were predicted using the DDI‐CPI server and Discovery Studio software. Molecular docking analysis revealed that Araloside C could be stably docked into the ATP/ADP‐binding domain of the heat shock protein 90 (Hsp90) protein via the formation of hydrogen bonds. The binding affinity of Hsp90 to Araloside C was detected using nanopore optical interferometry and yielded KD values of 29 μM. Araloside C also up‐regulated the expression levels of Hsp90 and improved cell viability in hypoxia/reoxygenation‐treated H9c2 cardiomyocytes, whereas the addition of 17‐AAG, a pharmacologic inhibitor of Hsp90, attenuated Araloside C‐induced cardioprotective effect. These findings reveal that Araloside C can efficiently attenuate myocardial I/R injury by reducing I/R‐induced oxidative stress and Ca2+i overload, which was possibly related to its binding to the Hsp90 protein.
In recent years, great improvements have been made on palladium‐catalyzed radical reactions. Emerging elegant methodologies of radical involved palladium‐catalyzed transformations provide more and ...more effective strategies for the construction of complex heterocyclic compounds and applications in drug discovery. It is universally known that Pd(0)/(II)/(IV)‐mediated reactions usually undergo two‐electron transfer processes, while the Pd(I) and Pd(III) involved reactions usually occur via single electron transfer processes. Since our review on palladium radical was published, numurous methodolgies involving palladium radical have sprung up in the past five years. This review further summarized the up‐to‐date transformations toward palladium radical from 2015. For most of these catalytic cycles strategies, plausible mechanisms are demonstrated in detail to give better insight for chemists in need.
Nitrogenous sesquiterpenoids fromnatural sourcesare rare, so unsurprisingly neither the potentially valuable bioactivity nor thebroad structural diversity of nitrogenous sesquiterpenoids has been ...reviewed before. This report covers the progressduring the decade from 2010 to February 2020 on the isolation, identification, and bioactivity of 391 nitrogen-containing natural sesquiterpenes from terrestrial plant, marine organisms, and microorganisms. This complete and in-depth reviewshouldbe helpful for discovering and developing new drugs of medicinal valuerelated to natural nitrogenous sesquiterpenoids.
Upconversion (UC) luminescent lanthanide nanoparticles (LNPs) are expected to play an important role in imaging and photodynamic therapy (PDT) in vitro and in vivo. However, with the absorption of UC ...emissions by photosensitizers (PSs) to generate singlet oxygen ((1)O2) for PDT, the imaging signals from LNPs are significantly weakened. It is important to activate another imaging route to track the location of the LNPs during PDT process. In this work, Nd(3+)-sensitized LNPs with dual-band visible and near-infrared (NIR) emissions under single 808 nm excitation were reported to address this issue. The UC emissions in green could trigger covalently linked rose bengal (RB) molecules for efficient PDT, and NIR emissions deriving from Yb(3+) and magnetic resonance imaging (MRI) were used for imaging simultaneously. Notably, the designed therapeutic platform could further effectively avoid the overheating effect induced by the laser irradiation, due to the minimized absorption of biological media at around 808 nm. TdT-mediated dUTP nick end labeling (TUNEL) assay showed serious cell apoptosis in the tumor after PDT for 2 weeks, leading to an effective tumor inhibition rate of 67%. Benefit from the PDT, the tumor growth-induced liver and spleen burdens were largely attenuated, and the liver injury was also alleviated. More importantly, pulmonary and hepatic tumor metastases were significantly reduced after PDT. The Nd(3+)-sensitized LNPs provide a multifunctional nanoplatform for NIR light-assisted PDT with minimized heating effect and an effective inhibition of tumor growth and metastasis.
Background: Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). ...However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. Methods: Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. Results: Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4–8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8–15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. Conclusions: Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.
Accurate and reliable monthly runoff forecasting plays an important role in making full use of water resources. In recent years, long short-term memory neural networks (LSTM), as a deep learning ...technology, has been successfully applied in forecasting monthly runoff. However, the hyperparameters of LSTM are predetermined, which has a significant influence on model performance. In this study, given that the decomposition of monthly runoff series may provide a more accurate prediction, as revealed by many previous studies, a hybrid model, namely, VMD-GWO-LSTM, is proposed for monthly runoff forecasting. The proposed hybrid model comprises two main components, namely, variational mode decomposition (VMD) coupled with the gray wolf optimizer (GWO)-based LSTM. First, VMD is utilized to decompose raw monthly runoff series into several subsequences. Second, GWO is implemented to optimize the hyperparameters of the LSTM for each subsequence on the condition that the inputs are determined. Finally, the total output of all subsequences is aggregated as the final forecast result. Four quantitative indices are employed to evaluate the model performance. The proposed model is demonstrated using 73 and 62 years of monthly runoff series data derived from the Xinfengjiang and Guangzhao Reservoirs in China's Pearl River system, respectively. To identify the feasibility and superiority of the proposed model, backpropagation neural networks (BPNN), support vector machine (SVM), LSTM, EMD-LSTM, VMD-LSTM and GWO-LSTM are also utilized for comparison. The results indicate that the proposed hybrid model can yield best forecast accuracy among these models, making it a promising new method for monthly runoff forecasting.
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