Cerebral hemodynamic change and metabolic alteration in severe hemorrhagic shock.

Understanding the biological mechanism and identifying biomarkers of hemorrhagic shock is important for diagnosis and treatment. We aim to use optical imaging to study how the cerebral blood circulation and metabolism change during the progression of severe hemorrhagic shock, especially the decompensatory stage. We used a multi-parameter (blood pressure (BP), cerebral blood flow (CBF), functional vascular density (FVD), blood oxygenation and mitochondrial NADH signal) cerebral cortex optical imaging system to observe brain hemodynamic change and metabolic alteration of rats in vivo for 4 h. Cerebral circulation and mitochondrial metabolism could be well preserved in the compensatory stage but impaired during the decompensatory stage. The changes of brain hemodynamics and metabolism may provide sensitive indicators for various shock stages including the transition from compensatory stage to decompensatory stage. Our novel imaging observations of hemodynamic and metabolic signals in vivo indicated that the rat brains under hemorrhagic shock suffered irreversible damage which could not be compensated by the autoregulation mechanism, probably due to injured mitochondria.

Exploring the effect of teacher autonomy support on Chinese EFL undergraduates' academic English speaking performance through the mediation of basic psychological needs and classroom engagement.

Introduction: The capacity to speak English for academic purposes is a pivotal facet of language education and assessment. Despite the substantial research approving the significant role of teachers in L2 learning, it remains unclear how exactly teachers' support for students' learning autonomy influences EFL learners' academic English speaking performance. Methods: To address this primary concern, this study drew ground from the Self-System Model of Motivational Development (SSMMD) and adopted a mixed-method approach to examine teacher autonomy support's direct and indirect effects on Chinese EFL undergraduates' academic English speaking performance through the mediation of basic psychological needs and classroom engagement. 247 first-year university students participating in academic English speaking courses were recruited in this study. Results and discussion: The quantitative results of the questionnaire indicated that students' perceived teacher support for autonomy directly predicted English speaking performance, and it also indirectly influenced students' speaking performance via the mediation of classroom engagement and basic psychological needs. Students' responses in the semi-structured interview further verified the positive effect of teacher autonomy support on academic English speaking development in the classroom. Pedagogical implications were also discussed based on the findings.

Simple and scalable preparation of lignin based porous carbon coated nano-clay composites and their efficient removal for the diversified iodine.

Here, lignin and nano-clay were used to prepare novel composite adsorbents by one-step carbonization without adding activators for radioactive iodine capture. Specially, 1D nano-clay such as halloysite (Hal), palygorskite (Pal) and sepiolite (Sep) were selected as skeleton components, respectively, enzymatic hydrolysis lignin (EHL) as carbon source, lignin based porous carbon/nano-clay composites (ELC-X) were prepared through ultrasonic impregnation, freeze drying, and carbonization. Characterization results indicated lignin based porous carbon (ELC) well coated on the surface of nano-clay, and made its surface areas increase to 252 m2/g. These composites appeared the micro-mesoporous hierarchical structure, considerable N doping and good chemical stability. Results of adsorption experiments showed that the introduction of ELC could well promote iodine vapor uptake of nano-clay, and up to 435.0 mg/g. Meanwhile, the synergistic effect between lignin based carbon and nano-clay was very significant for the adsorption of iodine/n-hexane and iodine ions, their capacity were far exceed those of a single material, respectively. The relevant adsorption kinetic and thermodynamics, and mechanism of ELC-X composites were clarified. This work provided a class of low-cost and environmentally friendly adsorbents for radioactive iodine capture, and opened up ideas for the comprehensive utilization of waste lignin and natural clay minerals.

Simultaneous detection of hemodynamics, mitochondrial metabolism and light scattering changes during cortical spreading depression in rats based on multi-spectral optical imaging.

Cortical spreading depression (CSD) is a self-propagating wave of cellular depolarization that plays an important role in the development of cerebral pathology following ischemia or trauma. Optical intrinsic signal (OIS) imaging has been widely used to investigate CSD. Sources of OIS are complex and related to the changes in brain tissue absorption and scattering. The absorbing chromophores may include oxy-hemoglobin, deoxy-hemoglobin, cytochromes, flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). Considering only one or part of these elements in studies involving OIS may cause inaccurate results. Thus, we simultaneously calculated changes in HbO, HbR, FAD, cytochrome c, cytochrome aa3 and light scattering during CSD by applying multi-spectral OIS imaging at 450, 470, 500, 530, 550, 570, 600, 630, and 650 nm in the rat brain. We also showed that the hemodynamic changes during CSD may not be correctly estimated if the scattering and other chromophores such as FAD, cytochrome c and cytochrome aa3, are not included in the fitting model of multi-wavelength data analysis. As shown in our results, if considering the changes in scattering and other chromophores in data fitting model, deoxy-hemoglobin (HbR) showed a triphasic change while only a monophasic decrease in HbR will be resolved without considering changes in scattering and other chromophores as reported in previous studies. Moreover, our results showed that changes in cytochrome c was tightly related to OIS at 550 nm, cytochrome aa3 was closely related to OIS at 450, 600 and 650 nm, and FAD was closely related to OIS at 450 and 470 nm during CSD. It indicates that if the contribution by these related chromophores is not considered, using OIS at these wavelengths to determine the hemoglobin changes during CSD may lead to inaccurate results.

Quality evaluation method for rat brain cryofixation on the basis of NADH fluorescence.

The goal of biological samples' cryofixation is to trap a metabolic state as it exists in vivo by rapidly stopping internal reactions. However, obtaining perfect quality of cryofixation for large and high hypermetabolism organ/tissue (such as brain, heart) remains a challenge. The aim of this study was to develop and display a comprehensive and direct method to evaluate cryofixation's process and quality. Here, we adopt a delicate combination of homemade cryo-imaging system with a rat cardiac arrest model that can control cryofixation time optionally. we successfully evaluate the cryofixation time-related nicotinamide adenine dinucleotide (NADH) fluorescence pattern of several coronal sections in rat's brain that suffered from directional funnel cryofixation procedure. Through quantitative analysis of the distribution map of NADH fluorescence, we could obtain a relationship between cryofixation time and well cryofixation volume and then could deduce the cryofixation rates and quality at different time points. Our results also demonstrated that dissection of the temporal muscle of rat could significantly optimize the classical direct funnel cryofixation protocol.

Efficient preparation of nitrogen-doped lignin-based carbon nanotubes and the selectivity of nitrogen speciation for photothermal therapy.

In this study, the lignin was pre-modified using small-molecule nitrogen-containing compounds, and then the nitrogen-doped lignin-based carbon nanotubes (L-NCNTs) were fabricated by pyrolysis using the modified lignin as raw materials. The obtained L-NCNTs were multi-walled carbon nanotubes with diameters between 10 and 80 nm. The modification of lignin had an important effect on the nitrogen morphology of L-NCNTs, and promoted the high selectivity of pyridine-N in the L-NCNTs. Defects and pyridinic-N structure were conducive to boosting photothermal properties of the L-NCNTs. The photothermal conversion efficiency of the L-NCNTs after 808 nm laser irradiation for 5 min reached 58.8 %. The L-NCNTs can be used as photothermal agents in drug delivery system to achieve mild photothermal therapy, and it is basically non-toxic to normal cells, indicating good biocompatibility. This work provides new ideas for development of lignin-based high value-added products from biomass.

Correcting the detrimental effects of nonuniform intensity distribution on fiber-transmitting laser speckle imaging of blood flow.

Laser speckle spatial contrast analysis (LSSCA) is superior to laser speckle temporal contrast analysis (LSTCA) in monitoring the fast change in blood flow due to its advantage of high temporal resolution. However, the application of LSSCA which is based on spatial statistics may be limited when there is nonuniform intensity distribution such as fiber-transmitting laser speckle imaging. In this study, we present a normalized laser speckle spatial contrast analysis (nLSSCA) to correct the detrimental effects of nonuniform intensity distribution on the spatial statistics. Through numerical simulation and phantom experiments, it is found that just ten frames of dynamic laser speckle images are sufficient for nLSSCA to achieve effective correction. Furthermore, nLSSCA has higher temporal resolution than LSTCA to respond the change in velocity. LSSCA, LSTCA and nLSSCA are all applied in the fiber-transmitting laser speckle imaging system to analyze the change of cortical blood flow (CBF) during cortical spreading depression (CSD) in rat cortex respectively, and the results suggest that nLSSCA can examine the change of CBF more accurately. For these advantages, nLSSCA could be a potential tool for fiber-transmitting/endoscopic laser speckle imaging.

Factors associated with post-operative delirium in hip fracture patients: what should we care.

BACKGROUND: The postoperative delirium is a common yet serious complication in elderly patients with hip fracture. We aimed to evaluate the potential risk factors of delirium in patients with hip fracture, to provide reliable evidence to the clinical management of hip fracture. METHODS: This study was a retrospective design. Elderly patients who underwent hip fracture surgery in our hospital from June 1, 2019 to December 30, 2020 were selected. The characteristics and treatment data of delirium and no delirium patients were collected and compared. Multivariate logistic regression analysis was performed to analyze the influencing factors affecting postoperative delirium in elderly patients with hip fracture. RESULTS: A total of 245 patients with hip fracture were included, the incidence of postoperative delirium in patients with hip fracture was 13.06%. There were significant differences in the age, BMI, history of delirium, estimated blood loss and duration of surgery (all p < 0.05). There were significant differences in the albumin and TSH between delirium and no delirium group (all p < 0.05), Logistics analyses indicated that age ≥ 75 years (OR 3.112, 95% CI 1.527-5.742), BMI ≥ 24 kg/m2 (OR 2.127, 95% CI 1.144-3.598), history of delirium (OR 1.754, 95% CI 1.173-2.347), estimated blood loss ≥ 400 mL (OR 1.698, 95% CI 1.427-1.946), duration of surgery ≥ 120 min (OR 2.138, 95% CI 1.126-3.085), preoperative albumin ≤ 40 g/L (OR 1.845, 95% CI 1.102-2.835) and TSH ≤ 2 mU/L (OR 2.226, 95% CI 1.329-4.011) were the independent risk factors of postoperative delirium in patients with hip fracture(all p < 0.05). CONCLUSIONS: Postoperative delirium is very common in elderly patients with hip fracture, and it is associated with many risk factors, clinical preventions targeted on those risk factors are needed to reduce the postoperative delirium.

Simultaneous monitoring of intracellular pH changes and hemodynamic response during cortical spreading depression by fluorescence-corrected multimodal optical imaging.

Cortical spreading depression (CSD) plays an important role in trauma, migraine and ischemia. CSD could induce pronounced hemodynamic changes and the disturbance of pH homeostasis which has been postulated to contribute to cell death following ischemia. In this study, we described a fluorescence-corrected multimodal optical imaging system to simultaneously monitor CSD associated intracellular pH (pH(i)) changes and hemodynamic response including hemoglobin concentrations and cerebral blood flow (CBF). CSD was elicited by application of KCl on rat cortex and direct current (DC) potential was recorded as a typical characteristic of CSD. The pH(i) shift was mapped by neutral red (NR) fluorescence which was excited at 516-556 nm and emitted at 625 nm. The changes in hemoglobin concentrations were determined by dual-wavelength optical intrinsic signal imaging (OISI) at 550 nm and 625 nm. Integration of fluorescence imaging and dual-wavelength OISI was achieved by a time-sharing camera equipped with a liquid crystal tunable filter (LCTF). CBF was visualized by laser speckle contrast imaging (LSCI) through a separate camera. Besides, based on the dual-wavelength optical intrinsic signals (OISs) obtained from our system, NR fluorescence was corrected according to our method of fluorescence correction. We found that a transient intracellular acidification followed by a small alkalization occurred during CSD. After CSD, there was a prolonged intracellular acidification and the recovery of pH(i) from CSD took much longer time than those of hemodynamic response. Our results suggested that the new multimodal optical imaging system had the potential to advance our knowledge of CSD and might work as a useful tool to exploit neurovascular coupling under physiological and pathological conditions.

Simultaneous automatic arteries-veins separation and cerebral blood flow imaging with single-wavelength laser speckle imaging.

Automatic separation of arteries and veins in optical cerebral cortex images is important in clinical practice and preclinical study. In this paper, a simple but effective automatic artery-vein separation method which utilizes single-wavelength coherent illumination is presented. This method is based on the relative temporal minimum reflectance analysis of laser speckle images. The validation is demonstrated with both theoretic simulations and experimental results applied to the rat cortex. Moreover, this method can be combined with laser speckle contrast analysis so that the artery-vein separation and blood flow imaging can be simultaneously obtained using the same raw laser speckle images data to enable more accurate analysis of changes of cerebral blood flow within different tissue compartments during functional activation, disease dynamic, and neurosurgery, which may broaden the applications of laser speckle imaging in biology and medicine.

A comparison of three approaches for laparoscopic single-site (LESS) myomectomy: conventional, robotic, and hand assisted.

The objective of this study is to determine the feasibility and explore criteria for patient selection for three methods of LESS myomectomy: conventional (C-LESS), robotic-assisted (RA-LESS), and hand-assisted (HA-LESS). This was a retrospective case review of 72 patients with uterine myomas, conducted in a large academic tertiary care hospital between March 1, 2015, and November 7, 2018. LESS myomectomy via conventional, robotic, and hand-assisted routes. 43 patients underwent C-LESS, 15 underwent RA-LESS, and 14 underwent HA-LESS, with no conversions to open abdominal myomectomy. The operative outcomes were compared across the three approaches. The HA-LESS group had the largest mean number (HA: 6.9; C: 3.7; RA: 2.9, P=0.001), diameter (HA: 11.3 cm; C: 9.3 cm; RA: 7.1 cm, P=0.035), and weight (HA: 850.1 g; C: 320.7 g; RA: 181.1 g, P=0.003) of myomas removed per patient. The use of this method was also found to have a direct correlation with estimated preoperative uterine size (HA: 20.1 weeks; C: 16.2 weeks; RA: 12.0 weeks, P=0.001. Operative time and postoperative stay were found to be not statistically different across groups. We conclude that all three types of LESS myomectomy are feasible with comparable surgical outcomes. Most importantly, our findings indicate that hand assistance can be combined with C-LESS myomectomy for large or multi-fibroid uterus without compromising operating time or patient recovery. Notably, we found that uterine size could be a useful tool for the determination of the surgical approach.

Investigating the effects of dimethylsulfoxide on hemodynamics during cortical spreading depression by combining laser speckle imaging with optical intrinsic signal imaging.

BACKGROUND AND OBJECTIVES: Cortical spreading depression (CSD) is an important pathological model to study cerebral ischemia and migraine. In pharmacological studies of CSD, dimethylsulfoxide (DMSO) is an efficient solvent for water-insoluble drugs. Previous studies indicated that DMSO could prevent pial arteriolar dilation induced by oxidants. Therefore, it was very important to study the effect of DMSO on hemodynamics during CSD so that optimization of dose of DMSO as solvent can be made. STUDY DESIGN/MATERIALS AND METHODS: DMSO was topically applied on the exposed rat cortex. Single CSD was elicited by controlled injection of KCl. Pial arteriolar diameter, cerebral blood flow, and direct current potential during CSD were monitored by optical intrinsic signal imaging, laser speckle imaging, and electrophysiology method, respectively. RESULTS: Topical application of DMSO (0.1%, 0.4%, 2%, and 4%, v/v) increased arteriolar resting diameter and resting blood velocity at all vascular compartments. In addition, both vasodilation and hyperemic response to CSD were attenuated by DMSO in a dose-dependent manner at doses from 0.1% to 4%. In contrast, the maximum value of blood velocity during CSD was not significantly affected by DMSO. CONCLUSION: The attenuation in hemodynamic response during CSD could possibly be caused by increased baseline value of vessel tone and blood velocity. Our findings suggest that when investigators use DMSO to dissolve water-insoluble, topically applied drugs in the hemodynamic study of CSD, dose of DMSO should be kept below 0.1% in order to avoid false results.

pH-Responsive Lignin-Based Nanomicelles for Oral Drug Delivery.

A pH-stimuli amphiphilic lignin-based copolymer was prepared, and it could self-assemble to form spherical nanomicelles with the addition of "switching" water. The morphology, structure, and physical properties of micelles were characterized with transmission electron microscopy (TEM), nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), particle-size analysis, and zeta-potential measurement. In vitro drug release exemplified that the micelles were pH-sensitive, retaining more than 84.36% ibuprofen (IBU) in simulated gastric fluid (pH 1.5) and presenting a smooth release of 81.81% IBU in simulated intestinal fluid (pH 7.4) within 72 h. Cell culture studies showed that the nanomicelles were biocompatible and boosted the proliferation of human bone marrow stromal cells hBMSC and mouse embryonic fibroblast cells NIH-3T3. Interestingly, the nanomicelles inhibited the survival of human colon cancer cells HT-29 with a final survival rate of only 5.34%. Therefore, this work suggests a novel strategy to synthesize intelligent lignin-based nanomicelles that show a great potential as oral drug carriers.

Preparation, characterization and evaluation of cellulose nanocrystal/poly(lactic acid) in situ nanocomposite scaffolds for tissue engineering.

Cellulose nanocrystal (CNC)/poly(lactic acid) (PLA) in situ nanocomposite scaffolds were fabricated by in situ polymerization of lactic acid and CNC which was directly utilized as aqueous suspension, followed by a process of thermally induced phase separation. The CNC/PLA in situ nanocomposite porous scaffolds were characterized by mechanical test, protein adsorption, hemolysis test, in vitro degradation measurement, TEM, FTIR, SEM and WAXD. Compared to the PLA scaffold, the CNC/PLA in situ nanocomposite scaffolds showed a greatly increased compression modulus, an improved hemocompatibility and protein adsorption capacity. The inclusion of CNCs boosted the in vitro degradation of the in situ nanocomposite porous scaffolds and facilitated the deposition of Ca2+, CO32-, PO43- ions in simulated body fluid. Furthermore, cell cultures were carried out on the CNC/PLA in situ nanocomposite porous scaffolds. In comparison with the PLA scaffold, the in situ nanocomposite scaffolds improved cell attachment and enhanced cell proliferation, denoting low cytotoxicity and good cytocompatibility. It can therefore be concluded that such scaffolds with excellent mechanical property, biocompatibility, biomineralization capacity and bioactivity hold great potential for bone tissue engineering.

A modified mini-stroke model with region-directed reperfusion in rat cortex.

Mini-ischemia localized into a specific brain area has promoted understanding of the mechanisms underlying brain recovery in stroke. However, the conventional mini-stroke model adopted permanent arterial ligations but lacked controllable reperfusion, which is crucial for the outcome of delayed functional recovery. In this study, we devised a new rat mini-stroke model in which the vascular ligations can be easily reversed to induce targeted reperfusion. Specifically, a flexible ring was incorporated into the conventional small arterial ligations to tighten the ligating loops and facilitate cutting the ligatures for sufficient reperfusion afterwards. The distribution of cerebral blood flow was explored directly through a cranial window using laser speckle contrast imaging. A distinct ischemic core, which well fits the profile of the ligated ring, was bordered by a penumbral zone and then together surrounded by nonischemic tissue immediately after the arterial ligations involving the ring. After cutting the ligatures, post-recanalization hyperperfusion occurred in the previous ischemic core and to a greater extent at 24 h after reperfusion. In contrast, recirculation of common carotid artery in the conventional mini-stroke model hardly altered hypoperfusion status within the ischemic core. Evidence from two kinds of control groups indicated that the ring might produce a compression effect on the underlying cortex and then contribute to the more highly localized infarct that was identified by triphenyltetrazolium chloride staining. Our data suggest that this model provides opportunities for investigating the neurovascular dynamics in acute stroke and rehabilitation, especially with emerging optical imaging techniques.

Acute hyperglycemia compromises cerebral blood flow following cortical spreading depression in rats monitored by laser speckle imaging.

Hyperglycemia and cortical spreading depression (CSD) are possible factors that worsen the outcome of ischemic stroke, and it is probable that there is a longterm cooperative effect of hyperglycemia and CSD on cerebral blood flow (CBF). Long-lasting and full-field observation of changes in CBF following CSD in vivo during acute hyperglycemia in rats might show whether this is the case. Here, we utilized laser speckle imaging to study influences of acute hyperglycemia on CBF at the level of individual vascular compartments for 3 h in normal rats and those with CSD. It is shown that there are extensive increases of CBF at the arteriole and parenchyma over the normal rat cortex during acute hyperglycemia, whereas there is no significant change in CBF at the venule. We also find that, at all vascular compartments, after the glucose administration there is a stepwise reduction of CBF following CSD, but after saline injection CBF following CSD is close to the baseline. Our results indicate that acute hyperglycemia could aggravate the severity of decrease in CBF following CSD, suggesting possible mechanisms by which hyperglycemia exacerbates cerebral damage after ischemic stroke.

Synthesis of fluorescent dendrimers with aggregation-induced emission features through a one-pot multi-component reaction and their utilization for biological imaging.

Hyperbranched polymers have attracted wide research attention owing to their unique topological structure, physicochemical properties and great potential for applications such asadditives, drug delivery, catalysts and nanotechnology. Among these, the polyamidoamine(PAMAM) dendrimers are some of the most important dendrimers. However, the synthesis and biomedical applications of fluorescent PAMAM dendrimers have received only limited attention. In this work, we present a rather effective and convenient approach for synthesis of fluorescent PAMAM dendrimers with aggregation-induced emission (AIE) properties through a one-pot catalyst-free Mannich reaction under rather mild experimental conditions (e.g., low reaction temperature, air atmosphere in the presence of water). The obtained AIE-active amphiphiles (PhE-PAD) could self-assemble into fluorescent organic nanoparticles (FONs). The obtained AIE-active FONs (PhE-PAD FONs) were fully characterized, and their successful construction was confirmed by 1H NMR spectroscopy, FT-IR spectroscopy and transmission electron microscopy. Fluorescence and UV-Visible absorption spectroscopy results demonstrated that the final PhE-PAD FONs showed strong yellow fluorescence, desirable photostability and good water dispersity. The cell viability evaluation and confocal laser scanning microscope imaging results suggested that PhE-PAD FONs possessed low cytotoxicity and excellent biocompatibility. Taken together, these results demonstrate that we have developed a facile and efficient strategy for the fabrication of AIE-active FONs, which possess many desirable features for biomedical applications.

Differentiating hemodynamic responses in rat primary somatosensory cortex during non-noxious and noxious electrical stimulation by optical imaging.

Nociception in the primary somatosensory (S1) cortex remains in need of further elucidation. The spatiotemporal comparison on changes of the cerebral blood volume evoked by graded peripheral electrical stimulation was performed in rat contralateral somatosensory cortex with optical intrinsic signal imaging (OISI, optical reflectance at 550 nm). Non-noxious electrical stimulus was applied with 5 Hz pulses (0.5 ms peak duration) for 2 s at the threshold current for muscle twitch, while noxious stimulus was delivered at currents of 10x and 20x amplitude of the predetermined threshold. Although the dimensions of peak response defined in the spatial domain (cerebral blood volume increase) in the S1 cortex presented no significant difference under non-/noxious stimuli, its early response component (about 1 s after stimulation onset) revealed by OISI technique was suggested to differentiate the loci of activated cortical region due to different stimulation in this study. The magnitude and duration of the optical intrinsic signal (OIS) response was found increasing with the varying stimulus intensity. Regions activated by the delivery of a noxious stimulus were surrounded by a ring of inverted optical intrinsic signal, the amplitude of that was inversely proportional to the strength of the optical signal attributable to activation. Intense stimuli significantly augmented the inverted optical signal in magnitude and spatial extent. These results indicated that noxious stimulation evoked different response patterns in the contralateral S1 cortex. The magnitude-dependent inverted optical signal might contribute to the differentiation of nociceptive input in the S1 cortex.

Peri-infarct temporal changes in intrinsic optical signal during spreading depression in focal ischemic rat cortex.

The changes of intrinsic optical signals (IOS) are one of the important parameters of spreading depression (SD). The relationship between cerebral blood flow (CBF) and IOS can provide useful information for understanding the role of SD in neurological disorders. Here, we combined laser speckle imaging (LSI), intrinsic optical signal imaging (IOSI), and electrophysiological recording techniques to study the effect of CBF before the occurrence of SD on the spatiotemporal characteristics of IOS related to SD in a ministroke model. Four kinds of temporal pattern of changes in IOS were observed at cortical locations with different level of the CBF before the occurrence of SD. The results indicate that in the surrounding of micro-infarcts, SD-associated IOS vary as a function of blood flow rate, suggesting that the characteristics of IOS during SD might reflect blood flow rates.