Search

Using our recently developed laser speckle contrast imaging (LSCI) to visualize blood vessels and monitor blood flow, here we test the utility of the chick embryo for drug screening. To this end, we examined the effects of antihypertensive agents Nifedipine and Amlodipine, belonging to the L-type calcium channel antagonist family, on blood flow visualized noninvasively through the intact shell. Guided by the live view mode, the drugs were injected through the shell and ventral to HH16-19 chick embryos. Our results show a significant reduction in the chick heart rate, blood flow, and vascular size within 5-20 minutes after Nifedipine or Amlodipine injection. For moderate Nifedipine concentrations, these parameters returned to initial values within 2-3 hours. In contrast, Amlodipine showed a rapid reduction in heart rate and blood flow dynamics at a more than ten times higher concentration than Nifedipine. These findings show that our LSCI system can monitor and distinguish the chick heart's response to injected drugs from the same family. This serves as proof-of-concept, paving the way for a rapid, cost effective, and quantitative test system for screening drugs that affect the cardiovascular system of live chick embryos. Live noninvasive imaging may also provide insights into the development and functioning of the vertebrate heart., Highlights: Non-invasive Laser Speckle Contrast Imaging (LSCI) of the chick chorioallantoic membrane (CAM) in whole incubated eggsSimultaneous recording images of the CAM, dynamics of blood flow, and heart rateLive view mode to identify size, heart position, and location of the embryo in the eggAutomated system for data acquisition and analysisLongitudinal quantification of the impact of a calcium channel antagonists, nifedipidine and amlodipine on the embryonic heart rate, CAM's blood flow, size and number of vessels.

Background: While the guidelines acknowledge the anticipated benefits of using an implantable cardioverter defibrillator (ICD) in individuals with catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the potential adverse effects have received less attention., Methods and Analysis: To address this issue comprehensively, we will explore various databases such as the Cochrane Library, Web of Science, EMBASE and PubMed. Our study will include CPVT patients, both with and without ICD implantation. Two researchers will evaluate the eligible studies independently and gather pertinent data. The quality of the studies included will be assessed using either the Newcastle-Ottawa Scale or the Cochrane Risk of Bias Tool. Data analysis will be conducted using RevMan., Ethics and Dissemination: Because this research depends exclusively on existing studies, obtaining patient informed consent and ethics approval is unnecessary. The results of this meta-analysis will be shared at conferences or in peer-reviewed journals., Prospero Registration Number: CRD42022370824., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Effective internal fixation with pedicle screw is a key factor in the success of lumbar fusion with internal fixation. Whether navigation robots can improve the efficacy and safety of screw placement is controversial. Thirty-eight patients who underwent oblique lateral lumbar interbody fusion internal fixation from March 2022 to May 2023 were retrospectively analyzed, 16 cases in the navigational robot group and 22 cases in the fluoroscopy group. Using visual analog score (VAS) for the low back and lower limbs, Oswestry Disability Index to compare the clinical efficacy of the 2 groups; using perioperative indexes such as the duration of surgery, intraoperative blood loss, intraoperative fluoroscopy times, and postoperative hospital stay to compare the safety of the 2 groups; and using accuracy of pedicle screws (APS) and the facet joint violation (FJV) to compare the accuracy of the 2 groups. Postoperative follow-up at least 6 months, there was no statistically significant difference between the 2 groups in the baseline data (P > .05). The navigational robot group's VAS-back was significantly lower than the fluoroscopy group at 3 days postoperatively (P < .05). However, the differences between the 2 groups in VAS-back at 3 and 6 months postoperatively, and in VAS-leg and Oswestry Disability Index at 3 days, 3 months, and 6 months postoperatively were not significant (P > .05). Although duration of surgery in the navigational robot group was significantly longer than in the fluoroscopy group (P > .05), the intraoperative blood loss and the intraoperative fluoroscopy times were significantly lower than in the fluoroscopy group (P < .05). The difference in the PHS between the 2 groups was not significant (P > .05). The APS in the navigation robot group was significantly higher than in the fluoroscopy group, and the rate of FJV was significantly lower than in the fluoroscopy group (P < .05). Compared with the traditional fluoroscopic technique, navigation robot-assisted lumbar interbody fusion with internal fixation provides less postoperative low back pain in the short term, with less trauma, less bleeding, and lower radiation exposure, as well as better APS and lower FJV, resulting in better clinical efficacy and safety., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Imaging blood vessels in early-stage avian embryos has a wide range of practical applications for developmental biology studies, drug and vaccine testing, and early sex determination. Optical imaging, such as brightfield transmission imaging, offers a compelling solution due to its safe non-ionizing radiation, and operational benefits. However, it comes with challenges, such as eggshell opacity and light scattering. To address these, we have revisited an approach based on laser speckle contrast imaging (LSCI) and demonstrated a high-quality, comprehensive, and non-invasive visualization of blood vessels in few-days-old chicken eggs, with blood vessels as small as 100 µm in diameter (with LSCI profile full-width-at-half-maximum of 275 µm). We present its non-invasive use for monitoring blood flow, measuring the embryo's heartbeat, and determining the embryo's developmental stages using machine learning with 85% accuracy from stage HH15 to HH22. This method can potentially be used for non-invasive longitudinal studies of cardiovascular development and angiogenesis, as well as egg screening for the poultry industry., Competing Interests: The authors declare no conflicts of interest., (© 2024 Optica Publishing Group.)

Background: Randomized controlled trials have demonstrated that Songling Xuemaikang capsule (SXC) is effective in blood pressure (BP) lowering for essential hypertension. However, the effectiveness of SXC in real-world clinical practice remains unknown. We aimed to investigate whether the BP-lowering effectiveness of SXC in the real-world practice setting is comparable to the efficacy of the intervention in a randomized controlled trial., Methods: We included 1325 patients treated with SXC monotherapy from a real-world registry and 300 from the SXC-BP trial. A propensity score matching (PSM) approach was used to select participants from the two cohorts. The primary outcome was a change in the office of BP from baseline to 8 weeks., Results: After PSM, there were 552 patients for the comparative analysis. Clinically meaningful BP reductions were observed both in the real world and in the RCT cohorts after 8-week SXC treatment. The 8-week systolic/diastolic BP was 129.50/81.33 mm Hg vs. 134.97/84.14 mm Hg in the real-world population and the RCT population, respectively. The changes in systolic BP (15.82 ± 10.71 vs. 10.48 ± 10.24; P  < .001), and diastolic BP (10.01 ± 7.73 vs. 7.75 ± 8.14; P  = .001) from baseline to 8 weeks were significantly greater in the real-world population., Conclusion: The current comparison demonstrated that SXC monotherapy is at least as effective in real-world settings as within the randomized controlled trial for BP lowering in patients with grade 1 hypertension.

Terminalia chebula Retz. (TCR) is a medicinal material commonly used in Mongolian medicine. After consulting the literature at home and abroad, current research on TCR focuses on chemical composition, pharmacodynamics, and fingerprints. The pharmacokinetics of TCR has not been reported. Cytochrome P450 (CYP450) is the main drug-metabolizing enzyme, and its activity may be induced or inhibited by certain drugs, resulting in drug interactions in clinical applications. The objective of this study was to establish a high performance liquid chromatography (HPLC) method that can simultaneously detect multiple probe drugs to determine the effect of TCR on the activities of CYP450 enzymes CYP2C19, CYP2E1, CYP2D6, CYP2C9, CYP3A4, and CYP1A2. Wistar rats (male) were divided into 5 groups according to the randomization principle, namely the control group, the positive group, and the high, medium and low dose group. After 15 days of continuous administration, the mixed probe drug was injected into the vein, and then a small amount of blood was collected from the orbital vein at different time points. After the samples were processed, the blood concentration of each probe drug was measured by the established HPLC method. The pharmacokinetic parameters of each probe drug were calculated using DAS software. Compared with the control group, the plasma clearance (CL) of chlorzoxazone and omeprazole decreased, and the maximum plasma concentration (C max ) and area under the curve (AUC) increased in the TCR group. The pharmacokinetic parameters of theophylline, midazolam, metoprolol, and tolbutamide did not differ significantly. The results indicated that TCR mainly inhibited the activities of CYP2E1 and CYP2C19, but had no effect on the activities of CYP1A2, CYP2C9, CYP3A4 and CYP2D6. Extra care should be taken when drugs metabolized by CYP2C19 and CYP2E1 enzymes are used in combination with TCR, as drug-herb interactions may occur. These results can guide the clinical application of related drugs and provide valuable information for drug interactions. The main component that affects enzyme activity may be tannins in the water extract., Competing Interests: None., (IJCEP Copyright © 2020.)

Aim: To examine phosphorylation of alphaB-crystallin (p-αBC), a vascular endothelial growth factor (VEGF) chaperone, and immunohistochemically investigate relationship between p-αBC, VEGF and phosphorylated p38-mitogen-activated protein kinase (p-p38 MAPK) in the epiretinal membrane of human proliferative diabetic retinopathy (PDR)., Methods: Eleven epiretinal membranes of PDR surgically excised were included in this study. Two normal retinas were also collected from enucleation tissues due to choroidal melanoma. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with anti-p-αBC, VEGF, CD31, and p-p38 MAPK antibodies., Results: Immunoreactivity for p-αBC was observed in all of the epiretinal membranes examined, where phosphorylation on serine (Ser) 59 showed strongest immunoreactivity in over 70% of the membranes. The immunolocalization of p-αBC was detected in the CD31-positive endothelial cells, and co-localized with VEGF and p-p38 MAPK in PDR membranes. Immunoreactivity for p-αBC, however, was undetectable in endothelial cells of the normal retinas, where p-p38 MAPK immunoreactivity was less marked than PDR membranes., Conclusion: Phosphorylation of αBC, in particular, phosphorylation on Ser59 by p-p38 MAPK may play a potential role as a molecular chaperon for VEGF in the pathogenesis of epiretinal membranes in PDR.

Aim: To examine the expression of αB-crystallin and vascular endothelial growth factor (VEGF) in conjunctival squamous cell carcinoma (CSCC)., Materials and Methods: Seven CSCCs and three normal conjunctivas that were surgically excised were studied. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with antibodies against αB-crystallin, its phosphorylated forms, and VEGF. In vitro experiments were conducted to investigate the effects of mitomycin C (MMC) treatment on the expression of αB-crystallin and VEGF secretion., Results: αB-Crystallin and VEGF were strongly expressed in CSCCs compared to normal conjunctivas. αB-Crystallin immunoreactivity was co-localized with that for VEGF in CSCCs, whereas these signals were reduced in CSCC tissues treated with MMC before excision. MMC treatment suppressed the αB-crystallin expression and VEGF secretion in cultured conjunctival cells in a dose-dependent manner., Conclusion: This study demonstrated αB-crystallin and VEGF expressions in human CSCCs, which may play a role in the pathogenesis. αB-Crystallin expression, and VEGF secretion were reduced by MMC, indicating a novel therapeutic mechanism in MMC treatment for human CSCC.