In Silico Evaluation of In Vivo Degradation Kinetics of Poly(Lactic Acid) Vascular Stent Devices.

Biodegradable vascular stents (BVS) are deemed as great potential alternatives for overcoming the inherent limitations of permanent metallic stents in the treatment of coronary artery diseases. The current study aimed to comprehensively compare the mechanical behaviors of four poly(lactic acid) (PLA) BVS designs with varying geometries via numerical methods and to clarify the optimal BVS selection. Four PLA BVS (i.e., Absorb, DESolve, Igaki-Tamai, and Fantom) were first constructed. A degradation model was refined by simply including the fatigue effect induced by pulsatile blood pressures, and an explicit solver was employed to simulate the crimping and degradation behaviors of the four PLA BVS. The degradation dynamics here were characterized by four indices. The results indicated that the stent designs affected crimping and degradation behaviors. Compared to the other three stents, the DESolve stent had the greatest radial stiffness in the crimping simulation and the best diameter maintenance ability despite its faster degradation; moreover, the stent was considered to perform better according to a pilot scoring system. The current work provides a theoretical method for studying and understanding the degradation dynamics of the PLA BVS, and it could be helpful for the design of next-generation BVS.

Immune cell early activation, apoptotic kinetic, and T-cell functional impairment in domestic pigs after ASFV CADC_HN09 strain infection.

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV.

A phenomenological model of pulsatile blood pressure-affected degradation of polylactic acid (PLA) vascular stent.

The stent implantation may alter the post-operative patient's blood pressure, and bioresorbable vascular stents (BVS) as a candidate to treat vascular diseases, its degradation is affected by mechanical stress, thus, the altered pressure representing varying stress level will result in different degradation behaviors of the BVS. This paper first proposed a novel stress-regulated PLA degradation model that included swelling factor, and then the degradation evolutions of a PLA BVS within 180 days under normal and high blood pressures were simulated by finite element method, and more four degradation indexes were defined to study the effects of the two blood pressures on the degradation of the PLA BVS. The results showed that the high pressure weakly accelerated the degradation of the PLA BVS with respect to the normal pressure by examining the four indexes, e.g., the residual stent volume v r ( t ) decreased to 0.72 and 0.69, respectively for the normal and high pressures at day 180. The current finding provided a theoretical understanding of the PLA BVS degradation, and hinted that the PLA BVS may not need to be elaborately selected in clinical practices for treating hypertensive patients.

A Versatile Disorder-to-Order Technology to Upgrade Polymers into High-Performance Bioinspired Materials.

Biodegradable polymer as traditional material has been widely used in the medical and tissue engineering fields, but there is a great limitation as to its inferior mechanical performance for repairing load-bearing tissues. Thus, it is highly desirable to develop a novel technology to fabricate high-performance biodegradable polymers. Herein, inspired by the bone's superstructure, a versatile disorder-to-order technology (VDOT) is proposed to manufacture a high-strength and high-elastic modulus stereo-composite self-reinforced polymer fiber. The mean tensile strength (336.1 MPa) and elastic modulus (4.1 GPa) of the self-reinforced polylactic acid (PLA) fiber are 5.2 and 2.1 times their counterparts of the traditional PLA fiber prepared by the existing spinning method. Moreover, the polymer fibers have the best ability of strength retention during degradation. Interestingly, the fiber tensile strength is even higher than those of bone (200 MPa) and some medical metals (e.g., Al and Mg). Based on all-polymeric raw materials, the VDOT endows bioinspired polymers with improved strength, elastic modulus, and degradation-controlled mechanical maintenance, making it a versatile update technology for the massive industrial production of high-performance biomedical polymers.

Senescent endothelial cells' response to the degradation of bioresorbable scaffold induces intimal dysfunction accelerating in-stent restenosis.

Atherosclerotic cardiovascular disease is a typical age-related disease accompanied by stiffening arteries. We aimed to elucidate the influence of aged arteries on in-stent restenosis (ISR) after the implantation of bioresorbable scaffolds (BRS). Histology and optical coherence tomography showed increased lumen loss and ISR in the aged abdominal aorta of Sprague-Dawley rats, with apparent scaffold degradation and deformation, which induce lower wall shear stress (WSS). This was also the case at the distal end of BRS, where the scaffolds degraded faster, and significant lumen loss was followed by a lower WSS. In addition, early thrombosis, inflammation, and delayed re-endothelialization were presented in the aged arteries. Degradation of BRS causes more senescent cells in the aged vasculature, increasing endothelial cell dysfunction and the risk of ISR. Thus, profoundly understanding the mechanism between BRS and senescent cells may give a meaningful guide for the age-related scaffold design. STATEMENT OF SIGNIFICANCE: The degradation of bioresorbable scaffolds aggravates senescent endothelial cells and a much lower wall shear stress areas in the aged vasculature, lead to intimal dysfunction and increasing in-stent restenosis risk. Early thrombosis and inflammation, as well as delayed re-endothelialization, are presented in the aged vasculature after bioresorbable scaffolds implantation. Age stratification during the clinical evaluation and senolytics in the design of new bioresorbable scaffolds should be considered, especially for old patients.

Reclamation intensifies the positive effects of warming on N2O emission in an alpine meadow.

Climatic warming can alter grassland nitrous oxide (N2O) emissions due to soil property alterations. However, how the reclamation affect grassland N2O flux under warming conditions remains unclear in alpine meadow ecosystems. We conducted a long-term manipulative warming experiment in a natural alpine meadow and a cultivated grassland on the Qinghai-Tibetan Plateau to explore the separate and interactive effects of warming and reclamation on the soil N2O emission flux. N2O fluxes were measured under four treatments including control (CK), warming (W), reclamation (R) and warming under reclamation (WR) from August 2018 to July 2019. We measured the content of soil C, N nutrients and 5 enzymatic activities in 2018 and 2019. Correlation analysis and structural equation modeling were used to clarify how soil N availability and soil enzyme activities affect N2O emission. Our results indicated that compared to the ambient conditions for the growing and non-growing seasons, soil N2O flux was significantly increased 59.1% and 152.0% by warming and 28.4% and 142.4% by reclamation, respectively. Compared with W, WR significantly increased N2O flux by 18.9% and 81.1% during the growing and non-growing seasons, respectively. Soil moisture was negatively correlated to enzymatic activity and N2O flux. Both warming and reclamation promoted soil nitrification by increasing related enzymatic activities that acted to increase the N2O flux. Reclamation resulted in a greater sensitivity of the activity of ammonia monooxygenase and hydroxylamine oxidoreductase to warming, thus enhancing the effects of warming on increasing the N2O flux. Our research indicated that reclamation can additionally increase the effects of warming on N2O emissions for alpine meadows. Therefore, excessive expansion of arable land should be avoided, and new reclamation sites should be planned scientifically, as warming is expected to intensify in the future.

Epidemiology and Genetic Characteristics of Porcine Reproductive and Respiratory Syndrome Virus in the Hunan and Hebei Provinces of China.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant threat to the pig industry in China. However, the epidemiological characteristics of PRRSV after the outbreak of African swine fever in China were not thoroughly investigated. In the present study, the serological and epidemiological investigations of PRRSV in pigs from the Hunan and Hebei provinces of China were assessed. The results showed that 73.12% (95% CI 71.74-74.49) of pigs were positive for PRRSV-special antibody by enzyme-linked immunosorbent assay. Out of 5799 samples, 482 (8.31%, 95% CI 7.60-9.02) samples were positive for PRRSV nucleic acids. The positive rates of PRRSV in healthy pigs from farms and slaughterhouses were 2.27% (47/2072) and 7.70% (217/2818), which were lower than that in diseased pigs (23.98%, 218/909). Furthermore, the full-length OFR5 gene sequences of 43 PRRSV strains were sequenced and analysed. Phylogenetic analysis revealed that 43 isolates were classified into three lineages, namely lineage 1 (n = 24), lineage 8 (n = 15), and lineage 3 (n = 4). Lineage 1 could be further divided into sublineage 1.5 (n = 2) and sublineage 1.8 (n = 22), and lineage 8 was classified into sublineage 8.1 (n = 3) and sublineage 8.7 (n = 12). Collectively, our findings revealed the severe prevalence of PRRSV in the Hunan and Hebei provinces, where sublineage 1.8 and sublineage 8.7 predominated. The present study provides the update information of the epidemiological and genetic characteristics of PRRSV in the investigated regions, which will be beneficial for PRRS control.

Temporal-spatial low shear stress induces heterogenous distribution of hematopoietic stem cell budding in zebrafish.

Hematopoietic stem/progenitor cells (HSPCs) originate from endothelial cells (ECs) localized on the ventral side of the dorsal aorta (DA), and hemodynamic parameters may suffer sharp changes in DA at HSPCs development stage for intersegmental vessel formation. However, the temporal-spatial shear stress parameters and biomechanics mechanisms of HSPC budding remain unknown. Here, we found that the hematopoietic endothelium (HE) in the aorta-gonad-mesonephros was heterogeneous; that is, HEs were mainly distributed at the ventral side of the vascular bifurcation in zebrafish embryos, which was found to show low shear stress (LSS) through numerical simulation analysis. Furthermore, HSPCs localized in the posterior somite of aorta-gonad-mesonephros with slow velocity. On the temporal scale, there was a slow velocity and LSS during HE budding from 36 h post-fertilization and decreased shear stress with drug expanded HSPC numbers. Mechanistically, matrix metalloproteinase (MMP) expression and macrophage chemotaxis were significantly increased in HEs by RNA-seq. After treatment with an MMP13 inhibitor, HSPCs were significantly reduced in both the aorta-gonad-mesonephros and caudal hematopoietic tissue in embryos. Our results show that HSPC budding is heterogeneous, and the mechanism is that physiological LSS controls the emergence of HSPCs by promoting the accumulation of macrophages and subsequent MMP expression.

Warming and spring precipitation addition change plant growth pattern but have minor effects on growing season mean gross ecosystem productivity in an alpine meadow.

Gross ecosystem productivity (GEP) plays an important role in global carbon cycling. However, how plant phenology and growth rate regulate GEP under climate change is unclear. Based on an in situ manipulative experiment using open top chambers from 2015 to 2018, we measured whole year warming and spring precipitation addition effects on plant phenology, plant growth rate and GEP. Our results showed that warming delayed plant green up (4 days) and withering (5 days), while spring precipitation addition advanced green up 13 days and did not change withering. Warming delayed the timing of the fast-growing phase 7 days, shortened length of the fast-growing phase 7 days and marginally increased the growth rate. Spring precipitation addition advanced the timing of the fast-growing phase 6 days, but did not change the length of the fast-growing phase or the growth rate. Both whole year warming and spring precipitation addition have not significantly affected growing season mean GEP. GEP is positively correlated with plant growth rate and negatively correlated with the length of the fast-growing phase. We provide an evidence that although warming did not change growing season mean productivity, it delayed plant fast-growing phase. Our findings suggest that management approaches for increasing water availability before the fast-growing phase should be intensified to increase ecosystem carbon uptake and grass supply for animal husbandry in spring.

Nitrogen Addition Affects Ecosystem Carbon Exchange by Regulating Plant Community Assembly and Altering Soil Properties in an Alpine Meadow on the Qinghai-Tibetan Plateau.

Nitrogen (N) deposition can affect the global ecosystem carbon balance. However, how plant community assembly regulates the ecosystem carbon exchange in response to the N deposition remains largely unclear, especially in alpine meadows. In this study, we conducted a manipulative experiment to examine the impacts of N (ammonium nitrate) addition on ecosystem carbon dioxide (CO2) exchange by changing the plant community assembly and soil properties at an alpine meadow site on the Qinghai-Tibetan Plateau from 2014 to 2018. The N-addition treatments were N0, N7, N20, and N40 (0, 7, 20, and 40 kg N ha-1year-1) during the plant growing season. The net ecosystem CO2 exchange (NEE), gross ecosystem productivity (GEP), and ecosystem respiration (ER) were measured by a static chamber method. Our results showed that the growing-season NEE, ER and GEP increased gradually over time with increasing N-addition rates. On average, the NEE increased significantly by 55.6 and 65.2% in N20 and N40, respectively (p < 0.05). Nitrogen addition also increased forage grass biomass (GB, including sedge and Gramineae) by 74.3 and 122.9% and forb biomass (FB) by 73.4 and 51.4% in N20 and N40, respectively (p < 0.05). There were positive correlations between CO2 fluxes (NEE and GEP) and GB (p < 0.01), and the ER was positively correlated with functional group biomass (GB and FB) and soil available N content (NO3 --N and NH4 +-N) (p < 0.01). The N-induced shift in the plant community assembly was primarily responsible for the increase in NEE. The increase in GB mainly contributed to the N stimulation of NEE, and FB and the soil available N content had positive effects on ER in response to N addition. Our results highlight that the plant community assembly is critical in regulating the ecosystem carbon exchange response to the N deposition in alpine ecosystems.

Biodegradable PTX-PLGA-coated magnesium stent for benign esophageal stricture: An experimental study.

Biodegradable stents can degrade step by step and thereby avoid secondary removal by endoscopic procedures in contrast to metal stents. Herein, a biodegradable composite stent, a magnesium (Mg)-based braided stent with a surface coating of poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX), was designed and tested. By adding this drug-loaded polymer coating, the radial force of the stent increased from 33 Newton (N) to 83 N. PTX was continuously released as the stent degraded, and the in vitro cumulative drug release in phosphate-buffered saline for 28 days was 115 ± 13.5 µg/mL at pH = 7.4 and 176 ± 12 µg/mL at pH = 4.0. There was no statistically significant difference in the viability of fibroblasts of stent extracts with different concentration gradients (P > 0.05), while the PTX-loaded stents effectively promoted fibroblast apoptosis. In the animal experiment, the stents were able to maintain esophageal patency during the 3-week follow-up and to reduce the infiltration of inflammatory cells and the amount of fibrous tissue. These results showed that the PTX-PLGA-coated Mg stent has the potential to be a safe and effective approach for benign esophageal stricture. STATEMENT OF SIGNIFICANCE: We designed a biodegradable composite stent, having poly (lactic-co-glycolic acid) (PLGA) containing paclitaxel (PTX) coated the surface of the magnesium (Mg)-based braided stent. We evaluated in vitro and in vivo characteristics of the Mg esophageal stent having a PLGA coating plus a variable concentration of PTX in comparison with the absence of PTX PLGA coating. The PTX PLGA stents exerted higher radial force than stents without coating, degraded more quickly in an acid medium, and effectively promoted fibroblast apoptosis in vitro experiments. In a rabbit model of caustic-induced esophageal stricture, there was an increased lumen and decreased inflammation of the esophageal wall in the animals stented with PTX-PLGA versus the sham group, indicating a potential approach for benign esophageal stricture.

Ventricular SK2 upregulation following angiotensin II challenge: Modulation by p21-activated kinase-1.

Effects of hypertrophic challenge on small-conductance, Ca2+-activated K+(SK2) channel expression were explored in intact murine hearts, isolated ventricular myocytes and neonatal rat cardiomyocytes (NRCMs). An established experimental platform applied angiotensin II (Ang II) challenge in the presence and absence of reduced p21-activated kinase (PAK1) (PAK1cko vs. PAK1f/f, or shRNA-PAK1 interference) expression. SK2 current contributions were detected through their sensitivity to apamin block. Ang II treatment increased such SK2 contributions to optically mapped action potential durations (APD80) and their heterogeneity, and to patch-clamp currents. Such changes were accentuated in PAK1cko compared to PAK1f/f, intact hearts and isolated cardiomyocytes. They paralleled increased histological and echocardiographic hypertrophic indices, reduced cardiac contractility, and increased SK2 protein expression, changes similarly greater with PAK1cko than PAK1f/f. In NRCMs, Ang II challenge replicated such increases in apamin-sensitive SK patch clamp currents as well as in real-time PCR and western blot measures of SK2 mRNA and protein expression and cell hypertrophy. Furthermore, the latter were enhanced by shRNA-PAK1 interference and mitigated by the PAK1 agonist FTY720. Increased CaMKII and CREB phosphorylation accompanied these effects. These were rescued by both FTY720 as well as the CaMKII inhibitor KN93, but not its inactive analogue KN92. Such CREB then specifically bound to the KCNN2 promoter sequence in luciferase assays. These findings associate Ang II induced hypertrophy with increased SK2 expression brought about by a CaMKII/CREB signaling convergent with the PAK1 pathway thence upregulating the KCNN2 promoter activity. SK2 may then influence cardiac electrophysiology under conditions of cardiac hypertrophy and failure.

A dataset of dual calcium and voltage optical mapping in healthy and hypertrophied murine hearts.

Pathological hypertrophy underlies sudden cardiac death due to its high incidence of occurrence of ventricular arrhythmias. The alteration of transmural electrophysiological properties in hypertrophic cardiac murine tissue has never been explored previously. In this dataset, we have for the first time conducted high-throughput simultaneous optical imaging of transmembrane potential and calcium transients (CaT) throughout the entire hypertrophic murine hearts at high temporal and spatial resolution. Using ElectroMap, we have conducted multiple parameters analysis including action potential duration/calcium transient duration, conduction velocity, alternans and diastolic interval. Voltage-calcium latency was measured as time difference between action potential and CaT peak. The dataset therefore provides the first high spatial resolution transmural electrophysiological profiling of the murine heart, allowing interrogation of mechanisms driving ventricular arrhythmias associated with pathological hypertrophy. The dataset allows for further reuse and detailed analyses of geometrical, topological and functional analyses and reconstruction of 2-dimensional and 3-dimentional models.

Impact of COVID-19 Pandemic on Intervals and Outcomes of Repeated Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma.

PURPOSE: Given that the novel coronavirus disease (COVID-19) pandemic has disrupted operations globally, an institution's ability to repeat transarterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) has also been affected. The aim of this study was to evaluate the impact of the COVID-19 on the intervals and outcomes of TACE in HCC patients. MATERIALS AND METHODS: This retrospective study included 154 HCC patients who underwent follow-up after TACE treatment from January 2020 to March 2020 (n = 71, study group) and January 2019 to March 2019 (n = 83, control group) at two institutions in China. The endpoints included the follow-up interval and overall response rate (ORR). Multivariate logistic regression analyses were performed to identify independent risk factors for a worse ORR. The cut-off point was determined to divide follow-up durations into long- and short-intervals. RESULTS: The median follow-up interval was 82.0 days (IQR, 61-109) in the study group, which was significantly longer than 66.0 days (IQR, 51-94) in the control group (P = 0.004). The ORR was 23.9 and 39.8% in the study and control group, respectively (P = 0.037). The cut-off value was 95 days. The grouping (OR, 2.402; 95% CI, 1.040-5.546; P = 0.040), long interval (OR, 2.573; 95% CI, 1.022-6.478; P = 0.045), and China liver cancer staging system (OR, 2.500; 95% CI, 1.797-3.480; P <0.001) were independent predictors for the efficacy of TACE treatment. CONCLUSIONS: The COVID-19 pandemic causes a longer follow-up interval in general, which may further lead to a lower ORR in HCC patients. Those with a follow-up interval of >95 days tend to have a worse prognosis.

Serological Investigation and Genetic Characteristics of Pseudorabies Virus in Hunan Province of China From 2016 to 2020.

Pseudorabies (PR), caused by variant pseudorabies virus (PRV), is an economically important viral disease in China. Recently, PRV infection in humans has also received attention worldwide. To investigate the PRV infection in Hunan province, China, we collected a total of 18,138 serum specimens from 808 PRV-vaccinated pig farms cross this region during 2016-2020, and we detected the presence of PRV glycoprotein B (gB) and gE-specific antibodies. The enzyme-linked immunosorbent assay (ELISA) results revealed that 80.47% (14,596/18,138, 95 CI 79.9-81.0) and 23.55% (4,271/18,138, 95 CI 22.9-24.2) of serum samples were positive for PRV gB and gE-specific antibodies, respectively. Further analysis indicated that the seroprevalence of wild PRV infection was associated with the season and breeding scale (p < 0.01). In addition, five PRV strains were isolated from PRV-positive samples in Vero cells and the virus titers varied from 106.5 to 107.51 TCID50/0.1 ml. The phylogenetic analysis revealed that one isolate was a classical strain of PRV genotype II, and four other isolates belonged to the variants of genotype II. Collectively, the data indicate that the prevalence of PRV remains high in pigs in Hunan province, and the variant PRV strains are the major genotypes affecting the development of the pig industry.

Effects of different positions of intravascular stent implantation in stenosed vessels on in-stent restenosis: An experimental and numerical simulation study.

Percutaneous coronary intervention (PCI) has been widely used in the treatment of atherosclerosis, while in-stent restenosis (ISR) has not been completely resolved. Studies have shown that changes in intravascular mechanical environment are related to ISR. Hence, an in-depth understanding of the effects of stent intervention on vascular mechanics is important for clinically optimizing stent implantation and relieving ISR. Nine rabbits with stenotic carotid artery were collected by balloon injury. Intravascular stents were implanted into different longitudinal positions (proximal, middle and distal relative to the stenotic area) of the stenotic vessels for numerical simulations. Optical coherence tomography (OCT) scanning was performed to reconstruct the three-dimensional configuration of the stented carotid artery and blood flow velocity waveforms were collected by Doppler ultrasound. The numerical simulations were performed through direct solution of Naiver-Stokes equation in ANSYS. Results showed that the distributions of time-averaged wall shear stress (TAWSS), oscillating shear index (OSI) and relative residual time (RRT) in near-end segment were distinctively different from other regions of the stent which considered to promote restenosis for all three models. Spearman rank-correlation analysis showed a significant correlation between hemodynamic descriptors and the stent longitudinal positions (rTAWSS = -0.718, rOSI = 0.898, rRRT = 0.818, p < 0.01). Histology results of the near-end segment showed neointima thickening deepened with the longitudinal positions of stent which was consistent with the numerical simulations. The results suggest that stent implantation can promote restenosis at the near-end segment. As the stenting position moves to distal end, the impact on ISR is more significant.

A Protocol for Dual Calcium-Voltage Optical Mapping in Murine Sinoatrial Preparation With Optogenetic Pacing.

Among the animal models for studying the molecular basis of atrial and sinoatrial node (SAN) biology and disease, the mouse is a widely used species due to its feasibility for genetic modifications in genes encoding ion channels or calcium handling and signaling proteins in the heart. It is therefore highly valuable to develop robust methodologies for studying SAN and atrial electrophysiological function in this species. Here, we describe a protocol for performing dual calcium-voltage optical mapping on mouse sinoatrial preparation (SAP), in combination with an optogenetic approach, for studying SAP membrane potential, intracellular Ca2+ transients, and pacemaker activity. The protocol includes the details for preparing the intact SAP, robust tissue dual-dye loading, light-programmed pacing, and high-resolution optical mapping. Our protocol provides an example of use of the combination of optogenetic and optical mapping techniques for investigating SAP membrane potential and intracellular Ca2+ transients and pacemaker activity with high temporal and spatial resolution in specific cardiac tissues. Thus, our protocol provides a useful tool for studying SAP physiology and pathophysiology in mice.

Cardiac Optogenetics and Optical Mapping - Overcoming Spectral Congestion in All-Optical Cardiac Electrophysiology.

Optogenetic control of the heart is an emergent technology that offers unparalleled spatio-temporal control of cardiac dynamics via light-sensitive ion pumps and channels (opsins). This fast-evolving technique holds broad scope in both clinical and basic research setting. Combination of optogenetics with optical mapping of voltage or calcium fluorescent probes facilitates 'all-optical' electrophysiology, allowing precise optogenetic actuation of cardiac tissue with high spatio-temporal resolution imaging of action potential and calcium transient morphology and conduction patterns. In this review, we provide a synopsis of optogenetics and discuss in detail its use and compatibility with optical interrogation of cardiac electrophysiology. We briefly discuss the benefits of all-optical cardiac control and electrophysiological interrogation compared to traditional techniques, and describe mechanisms, unique features and limitations of optically induced cardiac control. In particular, we focus on state-of-the-art setup design, challenges in light delivery and filtering, and compatibility of opsins with fluorescent reporters used in optical mapping. The interaction of cardiac tissue with light, and physical and computational approaches to overcome the 'spectral congestion' that arises from the combination of optogenetics and optical mapping are discussed. Finally, we summarize recent preclinical work applications of combined cardiac optogenetics and optical mapping approach.

Nomogram and Artificial Neural Network for Prognostic Performance on the Albumin-Bilirubin Grade for Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

PURPOSE: To construct the albumin-bilirubin (ALBI) grade and the Child-Turcotte-Pugh (CTP) score based on nomograms, as well as to develop an artificial neural network (ANN) to compare the prognostic performance of the 2 scores for hepatocellular carcinoma (HCC) that has undergone transarterial chemoembolization. MATERIALS AND METHODS: This multicentric retrospective study included patients with HCC who underwent transarterial chemoembolization monotherapy as an initial treatment at 4 institutions between January 2008 and December 2016. In the training cohort, significant risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The prognostic nomograms and ANN were established and then validated in 2 validation cohorts. RESULTS: A total of 838 patients (548, 115, and 175 in the training cohort and validation cohorts 1 and 2, respectively) were included. The median OS was 10.4, 15.7, and 9.2 months in the training cohort and validation cohorts 1 and 2, respectively. In the training cohort, both ALBI grade and CTP score were identified as significant risk factors. The ALBI grade and CTP score based on nomograms were established separately and showed similar prognostic performance when assessed externally in validation cohorts (C-index in validation cohort 1: 0.823 vs 0.802, P = .417; in validation cohort 2: 0.716 vs 0.729, P = .793). ANN showed that ALBI grade had higher importance on survival prediction than CTP score. CONCLUSIONS: ALBI grade performs at least no worse than CTP score regarding survival prediction for HCC receiving transarterial chemoembolization. Considering the easy application, ALBI grade has the potential to be regarded as an alternative to CTP score.

Multicentric Assessment of the Hong Kong Liver Cancer Staging System in Chinese Patients Following Transarterial Chemoembolization.

PURPOSE: We aimed to validate the performance of the hepatitis B-based Hong Kong Liver Cancer (HKLC) staging system compared with the Barcelona Clinic Liver Cancer (BCLC) staging system in Chinese hepatocellular carcinoma (HCC) patients treated with conventional transarterial chemoembolization (TACE) as the initial treatment. MATERIALS AND METHODS: The study was approved by the Institutional Review Boards at all participating centers. This retrospective study included 715 patients with HCC who underwent TACE as the initial treatment between January 2008 and December 2016 at three Chinese institutions. All of the patients calculated HCC stage using 5-substage HKLC (HKLC-5), 9-substage HKLC (HKLC-9), and the BCLC system. Based on overall survival (OS), these three staging systems' performance on treatment outcome prediction were compared using C statistic, Akaike information criterion (AIC), area under the receiver operating characteristic curve (AUC), linear trend Chi-square, likelihood ratio Chi-square, and calibration plots, respectively. RESULTS: The median OS was 10.1 months. Compared with the BCLC system, the HKLC system, especially HKLC-9, showed better performance on survival prediction (HKLC-9: C = 0.689, AIC = 6646.162; HKLC-5: C = 0.683, AIC = 6662.663; BCLC: C = 0.680, AIC = 6654.146), homogeneity (likelihood ratio Chi-square: HKLC-9 = 232.38, HKLC-5 = 215.87, and BCLC = 224.39, P < 0.001), and calibration (R2: HKLC-9 = 0.923, HKLC-5 = 0.916, and BCLC = 0.914). HKLC-9 outperformed on AUC at 6-, 12-, and 24-month survival prediction than HKLC-5 and BCLC. BCLC showed better performance on monotonicity (linear trend Chi-square: HKLC-9 = 121.641, HKLC-5 = 117.389, and BCLC = 125.752; P < 0.001). CONCLUSIONS: Combining survival prediction, discrimination, and calibration, the HKLC, especially HKLC-9 system, performed better for Chinese patients treated with TACE than the BCLC system.