Glycolytic PFKFB3 and Glycogenic UGP2 Axis Regulates Perfusion Recovery in Experimental Hind Limb Ischemia.

BACKGROUND: Despite being in an oxygen-rich environment, endothelial cells (ECs) use anaerobic glycolysis (Warburg effect) as the primary metabolic pathway for cellular energy needs. PFKFB (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase)-3 regulates a critical enzymatic checkpoint in glycolysis and has been shown to induce angiogenesis. This study builds on our efforts to determine the metabolic regulation of ischemic angiogenesis and perfusion recovery in the ischemic muscle. METHODS: Hypoxia serum starvation (HSS) was used as an in vitro peripheral artery disease (PAD) model, and hind limb ischemia by femoral artery ligation and resection was used as a preclinical PAD model. RESULTS: Despite increasing PFKFB3-dependent glycolysis, HSS significantly decreased the angiogenic capacity of ischemic ECs. Interestingly, inhibiting PFKFB3 significantly induced the angiogenic capacity of HSS-ECs. Since ischemia induced a significant in PFKFB3 levels in hind limb ischemia muscle versus nonischemic, we wanted to determine whether glucose bioavailability (rather than PFKFB3 expression) in the ischemic muscle is a limiting factor behind impaired angiogenesis. However, treating the ischemic muscle with intramuscular delivery of D-glucose or L-glucose (osmolar control) showed no significant differences in the perfusion recovery, indicating that glucose bioavailability is not a limiting factor to induce ischemic angiogenesis in experimental PAD. Unexpectedly, we found that shRNA-mediated PFKFB3 inhibition in the ischemic muscle resulted in a numerical increase in perfusion recovery and significantly higher vascular density compared with control shRNA (consistent with the increased angiogenic capacity of PFKFB3 silenced HSS-ECs). Based on these data, we hypothesized that inhibiting HSS-induced PFKFB3 in ischemic ECs activates alternative metabolic pathways that revascularize the ischemic muscle in experimental PAD. A comprehensive glucose metabolic gene qPCR arrays in PFKFB3 silenced HSS-ECs, and PFKFB3-inhibited ischemic muscle versus respective controls identified UGP2 (uridine diphosphate-glucose pyrophosphorylase 2), a regulator of protein glycosylation and glycogen synthesis, is induced upon PFKFB3 inhibition in vitro and in vivo. Antibody-mediated inhibition of UGP2 in the ischemic muscle significantly impaired perfusion recovery versus IgG control. Mechanistically, supplementing uridine diphosphate-glucose, a metabolite of UGP2 activity, significantly induced HSS-EC angiogenic capacity in vitro and enhanced perfusion recovery in vivo by increasing protein glycosylation (but not glycogen synthesis). CONCLUSIONS: Our data present that inhibition of maladaptive PFKFB3-driven glycolysis in HSS-ECs is necessary to promote the UGP2-uridine diphosphate-glucose axis that enhances ischemic angiogenesis and perfusion recovery in experimental PAD.

Artificial intelligence in the risk prediction models of cardiovascular disease and development of an independent validation screening tool: a systematic review.

BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

Pitfalls in Developing Machine Learning Models for Predicting Cardiovascular Diseases: Challenge and Solutions.

UNSTRUCTURED: In recent years, there has been an explosive development of artificial intelligence (AI), which has been widely applied in the healthcare field. As a typical AI technology, machine learning (ML) models have emerged as great potential in predicting cardiovascular diseases (CVDs) by leveraging large amounts of medical data for training and optimization, which are expected to play a crucial role in reducing the incidence and mortality rates of CVDs. Although the field has become a research hotspot, there are still many pitfalls that researchers need to pay close attention to. These pitfalls may affect the predictive performance, credibility, reliability, reproducibility of the studied models, ultimately reducing the value of the research and affecting the prospects for clinical application. Therefore, identifying and avoiding these pitfalls is a crucial task before implementing the research. However, there is currently a lack of comprehensive summary on this topic. This viewpoint aims to analyze the existing problems in terms of data quality, dataset characteristics, model design and statistical methods as well as clinic implication, and provide possible solutions to these problems, like gathering objective data, improving training, repeating measurements, increasing sample size, preventing overfitting using statistical methods, utilizing specific AI algorithms to address targeted issues, standardizing outcomes and evaluation criteria, as well as enhancing fairness and replicability, with the goal of offering reference and assistance to researchers, algorithm developers, policy makers, and clinical practitioners.

A nomogram for predicting choledochal cyst with perforation.

BACKGROUND: Choledochal cyst with perforation (CC with perforation) rarely occurs, early diagnosis and timely treatment plan are crucial for the treatment of CC with perforation. This study aims to forecast the occurrence of CC with perforation. METHODS: All 1111 patients were conducted, who underwent surgery for choledochal cyst at our hospital from January 2011 to October 2022. We conducted univariate and multivariate logistic regression analysis to screen for independent predictive factors for predicting CC with perforation, upon which established a nomogram. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) curves. RESULTS: The age of children with choledochal cyst perforation is mainly concentrated between 1 and 3 years old. Logistic regression analysis indicates that age, alanine aminotransferase, glutamyl transpeptidase, C-reactive protein, vomiting, jaundice, abdominal distension, and diarrhea are associated with predicting the occurrence of choledochal cyst perforation. ROC curves, calibration plots, and DCA curve analysis curves demonstrate that the nomogram has great discriminative ability and calibration, as well as significant clinical utility. CONCLUSION: The age of CC with perforation is mainly concentrated between 1 and 3 years old. A nomogram for predicting the perforation of choledochal cyst was established.

An Aerial Image Detection Algorithm Based on Improved YOLOv5.

To enhance aerial image detection in complex environments characterized by multiple small targets and mutual occlusion, we propose an aerial target detection algorithm based on an improved version of YOLOv5 in this paper. Firstly, we employ an improved Mosaic algorithm to address redundant boundaries arising from varying image scales and to augment the training sample size, thereby enhancing detection accuracy. Secondly, we integrate the constructed hybrid attention module into the backbone network to enhance the model's capability in extracting pertinent feature information. Subsequently, we incorporate feature fusion layer 7 and P2 fusion into the neck network, leading to a notable enhancement in the model's capability to detect small targets. Finally, we replace the original PAN + FPN network structure with the optimized BiFPN (Bidirectional Feature Pyramid Network) to enable the model to preserve deeper semantic information, thereby enhancing detection capabilities for dense objects. Experimental results indicate a substantial improvement in both the detection accuracy and speed of the enhanced algorithm compared to its original version. It is noteworthy that the enhanced algorithm exhibits a markedly improved detection performance for aerial images, particularly under real-time conditions.

1-D and 2-D Direction of Arrival Estimation in a Conical Conformal Array: Design and Implementation.

Direction of arrival (DOA) estimation for conformal arrays is challenging due to non-omnidirectional element patterns and shadow effects. Conical conformal array (CCA) can avoid the shadow effect at small elevation angles. So CCA is suitable for DOA estimation on both azimuth and elevation angles at small elevation angles. However, the element pattern in CCA cannot be obtained by conventional directional element coordinate transformation. Its local element pattern also has connection with the cone angle. The paper establishes the CCA radiation pattern in local coordinate system using 2-D coordinate transformation. In addition, in the case of large elevation angle, only half elements of the CCA can receive signal due to the shadow effect. The array degrees of freedom (DOF) are reduced by halves. We introduce the difference coarray method, which increases the DOF. Moreover, we propose a more accurate propagator method for 2-D cases. This method constructs a new propagation matrix and reduces the estimation error. In addition, this method reduces computational complexity by using linear computations instead of eigenvalue decomposition (EVD) and avoids spectral search. Simulation and experiment verify the estimation performance of the CCA. Both demonstrate the CCA model established in this paper is corresponding to the designed CCA antenna, and the proposed algorithms meet the needs of CCA angle detection. When the number of array elements is 12, the estimation accuracy is about 5 degrees.

Targeting the immune checkpoint B7-H3 for next-generation cancer immunotherapy.

Immune checkpoint inhibitors (ICIs) for programmed death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have become preferred treatment strategies for several advanced cancers. However, response rates for these treatments are limited, which encourages the search for new ICI candidates. Recent reports have underscored significant roles of B7 homolog 3 protein (B7-H3) in tumor immunity and disease progression. While its multifaceted roles are being elucidated, B7-H3 has already entered clinical trials as a therapeutic target. In this review, we overview the recent results of clinical trials evaluating the antitumor activity and safety of B7-H3 targeting drugs. On this basis, we also discuss the challenges and opportunities arising from the application of these drugs. Finally, we point out current gaps to address in the understanding of B7-H3 function and regulation in order to fully unleash the future clinical utility of B7-H3-based therapies for the treatment of cancer.

Circular RNA_0001495 increases Robo1 expression by sponging microRNA-527 to promote the proliferation, migration and invasion of bladder cancer cells.

Bladder cancer (BCa) is a heterogeneous disease that poses great threats on public health. Increasing studies have identified the vital functions of circular RNAs (circRNAs) in BCa treatment. Hence, this current study set out to explore the modulatory role of circ_0001495 in BCa development. First, the expression of circ_0001495 was determined by reverse transcription quantitative polymerase chain reaction. Cell biological processes were then analyzed after altering the circ_0001495 expression in T24 cells. Next, interactions among circ_0001495, microRNA-527 (miR-527) and roundabout guidance receptor 1 (Robo1) were investigated by dual luciferase reporter gene assay, RNA pull down assay and FISH assay. Lastly, xenograft tumors in nude mice were established to explore the effect of circ_0001495 in vivo. It was found that circ_0001495 was highly expressed in BCa tissues and cells, and was further correlated with poor prognosis in BCa patients. In addition, circ_0001495 inhibited the activity of miR-527 by acting as a sponge to sponge miR-527, which further elevated the Robo1 expression. Lastly, circ_0001495 was found to promote the proliferation, migration and invasion of BCa cells in vitro through the miR-527/Robo1 axis and promote the growth and metastasis of BCa tumors in vivo. Altogether, findings in our study highlight the promoting role of circ_0001495 in the progression of BCa by increasing Robo1 via sponging miR-527, representing a promising target for BCa management.

Revealing the tunability of electronic structures and optical properties of novel SWCNT derivatives, phenine nanotubes.

Single-walled carbon nanotubes (SWCNTs) have evoked great interest for various luminescent applications, but the large emission heterogeneity resulting from the structural complexity of the samples seriously restricts their further development. Herein we theoretically explore the electronic structures and optical properties of phenine nanotubes (pNTs), which are typical luminescent SWCNT derivatives with determined molecular structures that have been synthesized recently (Z. Sun, K. Ikemoto, T. M. Fukunaga, T. Koretsune, R. Arita, S. Sato and H. Isobe, Science, 2019, 363, 151-155; K. Ikemoto, S. Yang, H. Naito, M. Kotani, S. Sato and H. Isobe, Nat. Commun., 2020, 11, 1807). Interestingly, pNTs are found to feature different semiconducting properties to SWCNTs, as indicated by a spatial separation trend in the HOMO and LUMO resulting from periodic structural vacancies. The HOMO-LUMO and optical gaps of pNTs depend inversely on their lengths and diameters, but diameter variation should be an ineffective method for property tuning due to its negligible influence. By contrast, chemical modifications via N doping or hydrogenation highly affect the HOMO-LUMO gaps and their distributions and greatly broaden the light absorption/emission range, and importantly, low-dose hydrogenation is predicted to be a feasible strategy to enhance luminescence. This work, by studying the fundamental photophysical properties of pNTs and making comparisons to SWCNTs, shows the promise of structural vacancy engineering and surface functionalization in acquiring multifunctional tube-like materials.

Distribution Characteristics of Ground Echo Amplitude and Recognition of Signal Grazing Angle.

With the continuous advancement of electronic technology, terahertz technology has gradually been applied on radar. Since short wavelength causes severe ground clutter, this paper studies the amplitude distribution statistical characteristics of the terahertz radar clutter based on the measured data, and provides technical support for the radar clutter suppression. Clutter distribution is the function of the radar glancing angle. In order to achieve targeted suppression, in this paper, selected axial integral bispectrum (selected AIB) feature is selected as deep belief network (DBN)input to complete the radar glancing angle recognition and the network structure, network training method, robustness are analyzed also. The ground clutter amplitude distribution can follow normal distribution at 0~45° grazing angles. The Weibull distribution and G0 distribution can describe the amplitude probability density function of ground clutter at grazing angles 85° and 65°. The recognition rate of different signal grazing angles can reach 91% on three different terrains. At the same time, the wide applicability of the selected AIB feature is verified. The analysis results of ground clutter amplitude characteristics play an important role in the suppression of radar ground clutter.

Effect of humour intervention programme on depression, anxiety, subjective well-being, cognitive function and sleep quality in Chinese nursing home residents.

AIM: To evaluate the effect of an 8-week humour intervention programme on reducing depression and anxiety and improving subjective well-being, cognitive function and sleep quality in nursing home residents. DESIGN: A single-blinded and quasi-experimental design with repeated measures. METHODS: Seventy-four older adults were recruited from May 2018-September 2018, with 37 older adults in the humour group received humour intervention and 37 in the control group received no intervention. The intervention was an 8-week humour intervention programme for older adults to learn to use humour and release their emotions. Primary outcomes include depression, anxiety and subjective well-being and secondary outcomes were cognitive function and sleep quality. Two-way repeated measures ANOVA was used to compare the differences of outcome measures between the two groups. Outcomes were measured at baseline, 8 and 16 weeks. RESULTS: There was no significant difference between the two groups at baseline. The adherence to the sessions of humour intervention over the 8-weeks was 97.6%. Two-way repeated measures ANOVA revealed significant improvement in depression, anxiety, subjective well-being and sleep quality during the postintervention (8 weeks) and follow-up (16 weeks) periods in the humour group versus the control group. However, a significant time × group interaction for cognitive function was only found during postintervention. CONCLUSION: The humour intervention programme was effective in reducing depression and anxiety symptoms and increasing subjective well-being, cognitive function and sleep quality in older adults. IMPACT: Physical and mental health problems are common among older adults in nursing homes. The study demonstrated that humour intervention has feasibility and potential to be used as an effective non-pharmacological intervention in improving well-beings of Chinese nursing home residents. TRIAL REGISTRATION: ChiCTR1800016148.

A convenient one-pot nanosynthesis of a C(sp2)-C(sp3)-linked 3D grid via an 'A2 + B3' approach.

Fluorene-based 3D-grid-FTPA was synthesised with a total yield of 55% via the one-pot formation of six C(sp2)-C(sp3) bonds through a BF3·Et2O-mediated Friedel-Crafts reaction of A2-type bifluorene tertiary alcohol (BIOH) and two B3-type triphenylamines. At the same time, Un-grid-FTPA (2.7%) and 2D-grid-FTPA (5.6%) were obtained as by-products from this synthesis method. In addition, the effect of stereoisomers of BIOH was evaluated to demonstrate that Rac-BIOH is a better A2-type building block to prepare 3D-grid-FTPA in a relatively high yield. Furthermore, 3D-grid-FTPA showed excellent chemical, thermal, and photo-stabilities.

The effect of whole body vibration on health-related quality of life in patients with chronic conditions: a systematic review.

PURPOSE: To identify the effects of whole body vibration (WBV) on health-related quality of life (HRQOL) in patients with chronic conditions. METHODS: Five databases (the Cochrane Library, PubMed, Medline, EBSCO, and Web of science) were searched (from inception until April 30, 2019) for original articles. All studies were randomized controlled trials reporting the effects of WBV on HRQOL. Two independent reviewers extracted trial data and assessed the risk of bias using the risk of bias tool recommended by the Cochrane Back Review Group. RESULTS: Of the 349 articles that were screened, 17 articles, including 763 participants with various chronic conditions, met the inclusion criteria. Six studies reported significant improvements in HRQOL. No evidence was observed to suggest that WBV was more effective than other types of exercises. The study participants, exercise protocols, HRQOL instruments, study duration, and frequency as well as amplitude of WBV varied across the studies. Meta-analysis was not conducted due to the heterogeneity of study designs and outcome measures. CONCLUSIONS: This study has demonstrated that WBV may improve HRQOL in patients with chronic conditions. However, the evidence was not strong enough to warrant recommendation and thus further high-quality studies with larger sample sizes and longer intervention durations are needed.

A meta-analysis of randomized controlled trials of laughter and humour interventions on depression, anxiety and sleep quality in adults.

AIM: To quantify the effect of laughter and humour interventions on depression, anxiety, and sleep quality in adults. DESIGN: A meta-analysis of randomized controlled trials. DATA SOURCES: PubMed, Embase, PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Weipu, and Wanfang Data were searched from their inception up to December 2018. REVIEW METHODS: The reporting of this meta-analytical review was conducted according to the guidelines of the Cochrane Collaboration. Two reviewers selected the studies, extracted the data, and evaluated the risk of bias (Cochrane Collaboration bias assessment tool) of the included papers independently. RESULTS: Ten studies comprising 814 participants were included. Meta-analysis showed that these interventions significantly decreased adults' depression, anxiety, and improved their sleep quality. The results of subgroup analysis showed that depression benefits more from long-term laughter intervention. CONCLUSIONS: This meta-analysis revealed that laughter and humour interventions are effective in relieving depression, anxiety, and improve sleep quality in adults. More studies with high quality and follow-up assessment should be conducted for future research. IMPACT: This review synthesized current evidence using laughter and humour interventions to reduce negative emotion and promote better results in adults, especially with respect to target the applicability between different populations or intervention methods. In addition, humour and laughter interventions are safe, convenient, interesting and can promote interpersonal relationship in both patients and medical workers, which have great feasibility and potential to be used as an aspect of psychotherapy for clinical and nursing to improve well-beings in adults.

Overexpression of miR-210 promotes the potential of cardiac stem cells against hypoxia.

OBJECTIVE: To evaluate the effects of miR-210 on cardiac stem cells (CSCs) against hypoxia-induced injury. METHODS: CSCs were isolated from rat ventricular wall and cultured until passage 4. After exposure to hypoxia for 6 h, the expression of miR-210 was determined. Thereafter, transfection of miR-210 mimic and inhibitor was carried out. 1 week later, in vitro experiments were performed to measure the expression of caspase-8-associated protein 2 (Casp8ap2), Caspase 8, protein tyrosine phosphatase, non-receptor type 2 (PTPN2) and CXC chemokine receptor 4 (CXCR4), as well as migration and apoptosis of CSCs under hypoxic condition. RESULTS: Hypoxia induced a significant up-regulation of miR-210 expression in CSCs. Notably, the expression of Casp8ap2, Caspase8, PTPN2 was dramatically inhibited by overexpression of miR-210 in CSCsmiR-210 Group (P < .05), but no changes in CXCR4 (P > .05), compared with the control. Additionally, a decreased apoptosis of CSCs was detected in CSCsmiR-210 Group (26.22 ± 1.15%, P < .001), compared with Control Group (34.97 ± 0.63%). Moreover, the migration of CSCs was significantly promoted in CSCsmiR-210 Group (45.73 ± 2.4, P < .001), compared with Control Group (19.6 ± 1.11). Meanwhile, down-regulation of miR-210 reversed these results (P < .05). CONCLUSIONS: miR-210 was a hypoxia responsive element in CSCs, and its up-regulation inhibited apoptosis of CSCs and promoted their migration under hypoxic condition, through regulating its target genes Casp8ap2/Caspase 8 and PTPN2, which may provide a new strategy for cell therapy of ischemic heart disease.

A novel augmented venous-drainage model of cardiopulmonary bypass for deep hypothermic circulatory arrest without blood priming.

OBJECTIVE: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are commonly used in cardiac surgery. However, the mortality and morbidity are still high in practice. Developing novel protective stategies and elucidating the underlying mechanisms for the pathophysiological consequences of DHCA have been hampered because of the absence of a satisfactory recovery animal model. The aim of this study was to establish a novel and safe DHCA model without blood priming in rats to study the pathophysiology of potential complications. METHODS: Ten adult male Sprague-Dawley rats (age, 14-16 weeks; weight, 200-300g) were used. The entire CPB circuit consisted of a modified reservoir, a custom-designed small-volume membrane oxygenator, a roller pump and a home-made heat exchanger, all of which were connected via silicon tubing. The volume of the priming solution was less than 10 ml. The right jugular vein, right carotid artery and left femoral artery were cannulated. The blood was drained from the right atrium through the right jugular vein and fed back to the rat via the left femoral artery. CPB was commenced at a full flow rate. The animals were cooled to a pericranial temperature of 18°C and then subjected to 45 minutes of DHCA with global ischemia. Circulatory arrest was followed by rewarming and over 60 minutes of reperfusion. CPB was terminated carefully. Blood in the circuit was centrifuged and slowly transfused to achieve optimal hematocrit. Blood gas and hemodynamic parameters were recorded at each time point before CPB, during CPB and after CPB. RESULTS: All CPB and DHCA processes were achieved successfully. No rat died in our research. Blood gas analyses at different times were normal. Cardiac function and blood pressure were stable after the operation. The vital signs of all the rats were stable. CONCLUSION: The novel augmented venous-drainage CPB and DHCA model in rats could be established successfully without blood priming.

Antegrade Versus Continuous Retrograde del Nido Cardioplegia in the David I Operation.

BACKGROUND: The efficacy of continuous retrograde del Nido cardioplegia for myocardial protection is still controversial. We hypothesised that antegrade and retrograde cardioplegia offer equivalent safety for myocardial protection in the David I procedure. METHODS: We retrospectively reviewed 33 patients undergoing the David I operation with antegrade or retrograde del Nido solution from June 2014 to January 2016. The outcomes were compared. The follow-up was 1 month to 15 months. RESULTS: There was no hospital mortality or reoperation in both groups. Cardiopulmonary bypass, and aortic clamp times were similar. Troponin I level (TnI), creatine kinase level (CKMB), left ventricular ejection fraction (LVEF), ventilation times, intensive care unit (ICULOS) and hospital stay times (THLOS) were similar between the two groups. The lactate level was slightly higher (9.26±2.56 vs 7.17±1.58, p=0.01) in the antegrade group compared with the retrograde group. The incidence of heart block was higher (four patients) in the retrograde group (26.7% vs 0%, p=0.019). Only one patient (6.7%) required implantation of a permanent cardiac pacemaker. CONCLUSION: Antegrade and continuous retrograde del Nido cardioplegia can be used safely and effectively in the David I operation. The continuous retrograde del Nido cardioplegia is associated with a higher rate of temporary AV block which does not require permanent pacing, and a lower lactate level.

Unbalanced synaptic inputs underlying multi-peaked frequency selectivity in rat auditory cortex.

By measuring the frequency selectivity at different intensities in the primary auditory cortex of adult rats, we found that a small group of cortical neurons can exhibit relatively weak but robust selectivity at multiple frequencies that are different from the most preferred frequency. Both in vivo multi-unit recordings (26/93 recordings) and single-unit recordings (16/137 neurons) confirmed that the preferred frequencies are periodic and have an averaged bandwidth (BW) of 0.3-0.4 octaves, which leads to multi-peaked frequency selectivity. Interestingly, the averaged bandwidth of the ripple in the frequency response tuning curve was invariant with the sound intensity. An investigation of the synaptic currents in vivo also revealed similar multi-peaked frequency selectivity for both excitation and inhibition. While the excitatory and inhibitory inputs were relatively balanced for most frequencies, the ratio between excitation and inhibition at the peak and valley of each ripple was highly unbalanced. Since this multi-peaked frequency selectivity can be observed at the synaptic, single-cell, and population levels, our results reveal a potential mechanism underlying the multi-peaked pattern of frequency selectivity in the primary auditory cortex.

Osteoprotective Effect of Radix Scutellariae in Female Hindlimb-Suspended Sprague-Dawley Rats and the Osteogenic Differentiation Effect of Its Major Constituent.

A number of medicinal herbs have demonstrated therapeutic effects for the prevention and treatment of disuse-induced osteoporosis. As a common ingredient in proprietary traditional Chinese medicines, the anti-osteoporosis effects of Radix Scutellariae extract (RSE, 50 mg/kg/day) were evaluated in a hindlimb suspended rat model. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and the micro-architecture observed by MicroCT assay with bone biomechanical properties evaluated by a three-point bending test. To elucidate potential mechanisms, the osteogenic differentiation effect of baicalin as the most abundant ingredient in RSE was investigated in rat bone marrow derived mesenchymal stem cells (rBMSC). After drug administration for 42 days, tibia-BMD was significantly increased to 0.176 ± 0.007 and 0.183 ± 0.011 g/cm² and f-BMD was enhanced to 0.200 ± 0.017 and 0.207 ± 0.021 g/cm² for RSE and ALE treatment, respectively, whereas tibia-BMD and femur-BMD of the HLS group were 0.157 ± 0.009 and 0.176 ± 0.008 g/cm². Deterioration of bone trabecula microstructure was improved by RSE and ALE with increased morphological parameters such as bone volume fraction, trabecular thickness, and trabecular number, as well as connectivity density compared to the HLS group (p < 0.01). A three-point bending test suggested that bone mechanical strength was also enhanced by RSE and ALE treatments with increased maximum stress, young's modulus, maximum load, and stiffness compared to those of the HLS group (p < 0.05). Besides, serum TRACP levels were significantly suppressed by RSE and ALE treatments. Furthermore, in vitro studies demonstrated that baicalin significantly increased ALP activities and the formation of mineralized nodules in rBMSC. Conclusively, supplementation of RSE could significantly prevent weightlessness induced osteoporosis, which might attribute to the osteogenic differentiation enhancement effect of baicalin.