Dexmedetomidine preconditioning alleviates apoptosis in rat cardiomyocytes by suppressing programmed cell death 4 (PDCD4) after myocardial ischemia-reperfusion injury

Purpose: To determine the role of dexmedetomidine (Dex) in hypoxia/reoxygenation (H/R)-induced myocardial cell injury and the possible involvement of the programmed cell death 4 (Pdcd4) gene in Dex-mediated myocardial cell apoptosis after ischemia-reperfusion (I/R) injury. Methods: An in vivo I/R-injured rat model and in vitro H/R rat cell model were evaluated to ascertain the role of Dex in apoptosis. Programmed cell death 4 (PDCD4) gene expression levels were measured after Dex preconditioning. The effects of Pdcd4 knockdown or overexpression on Dex-mediated apoptosis during H/R injury were determined. Results: Dex pretreatment alleviated myocardial infarction in rats, suppressed myocardial cell apoptosis, and inhibited PDCD4 expression (p < 0.05). Treatment with Dex also alleviated H/R-induced apoptosis in rat cardiomyocytes, while PDCD4 expression decreased after Dex treatment (p < 0.05). Moreover, PDCD4 overexpression reversed the inhibitory effect of Dex on H/R myocardial cell apoptosis. Conclusion: Dex alleviates myocardial infarction in rats via its effect on PDCD4 expression. Therefore, Dex can potentially be used for the treatment but this has to clinical studies

Landmark Tracking in Liver US images Using Cascade Convolutional Neural Networks with Long Short-Term Memory

This study proposed a deep learning-based tracking method for ultrasound (US) image-guided radiation therapy. The proposed cascade deep learning model is composed of an attention network, a mask region-based convolutional neural network (mask R-CNN), and a long short-term memory (LSTM) network. The attention network learns a mapping from a US image to a suspected area of landmark motion in order to reduce the search region. The mask R-CNN then produces multiple region-of-interest (ROI) proposals in the reduced region and identifies the proposed landmark via three network heads: bounding box regression, proposal classification, and landmark segmentation. The LSTM network models the temporal relationship among the successive image frames for bounding box regression and proposal classification. To consolidate the final proposal, a selection method is designed according to the similarities between sequential frames. The proposed method was tested on the liver US tracking datasets used in the Medical Image Computing and Computer Assisted Interventions (MICCAI) 2015 challenges, where the landmarks were annotated by three experienced observers to obtain their mean positions. Five-fold cross-validation on the 24 given US sequences with ground truths shows that the mean tracking error for all landmarks is 0.65+/-0.56 mm, and the errors of all landmarks are within 2 mm. We further tested the proposed model on 69 landmarks from the testing dataset that has a similar image pattern to the training pattern, resulting in a mean tracking error of 0.94+/-0.83 mm. Our experimental results have demonstrated the feasibility and accuracy of our proposed method in tracking liver anatomic landmarks using US images, providing a potential solution for real-time liver tracking for active motion management during radiation therapy

Hepatoprotective Effect of Polyphenol-Enriched Fraction from Folium Microcos

Folium Microcos (FM), the leaves of Microcos paniculata L., shows various biological functions including antioxidant activity and α-glucosidase inhibitory effect. However, its therapeutic potential in acute liver injury is still unknown. This study investigated the hepatoprotective effect and underlying mechanisms of the polyphenol-enriched fraction (FMF) from Folium Microcos. FMF exhibited strong free radical scavenging activities and prevented HepG2/Hepa1–6 cells from hydrogen peroxide- (H2O2-) induced ROS production and apoptosis in vitro. Antioxidant activity and cytoprotective effects were further verified by alleviating APAP-induced hepatotoxicity in mice. Western blot analysis revealed that FMF pretreatment significantly abrogated APAP-mediated phosphorylation of MAPKs, activation of proapoptotic protein caspase-3/9 and Bax, and restored expression of antiapoptotic protein Bcl2. APAP-intoxicated mice pretreated with FMF showed increased nuclear accumulation of nuclear factor erythroid 2-related factor (Nrf2) and elevated hepatic expression of its target genes, NAD(P)H:quinine oxidoreductase 1 (NQO1) and hemeoxygenase-1(HO-1). HPLC analysis revealed the four predominantly phenolic compounds present in FMF: narcissin, isorhamnetin-3-O-β-D-glucoside, isovitexin, and vitexin. Consequently, these findings indicate that FMF possesses a hepatoprotective effect against APAP-induced hepatotoxicity mainly through dual modification of ROS/MAPKs/apoptosis axis and Nrf2-mediated antioxidant response, which may be attributed to the strong antioxidant activity of phenolic components

The relationship between red blood cell distribution width at admission and post-stroke fatigue in the acute phase of acute ischemic stroke

IntroductionPost-stroke fatigue (PSF) is a common complication in the patients with acute ischemic stroke (AIS). This prospective study aimed to investigate the relationship between red blood cell distribution width (RDW) at admission and PSF in the acute phase.MethodsThe AIS patients were enrolled in Nantong Third People's Hospital, consecutively. PSF in the acute phase was scored according to the Fatigue Severity Scale. Levels of RDW were measured at admission. The associations were analyzed using multivariate regression and restricted cubic splines (RCS).ResultsFrom April 2021 to March 2022, a total of 206 AIS patients (mean age, 69.3 ± 10.7 years; 52.9% men) were recruited. After the adjustment for potential confounding factors, RDW at admission remained the independent associated factor with PSF in the acute phase (OR [odds ratio], 1.635; 95% CI [confidence interval], 1.153–2.318; P = 0.006). The linear dose-response associations of RDW with PSF in the acute phase were found, based on the RCS model (P for non-linearity = 0.372; P for linearity = 0.037). These results remained significant in other models.ConclusionsRDW at admission could serve as a novel biomarker of PSF in the acute phase of AIS

Case Report: A Novel GJB2 Missense Variant Inherited From the Low-Level Mosaic Mother in a Chinese Female With Palmoplantar Keratoderma With Deafness

Dominant variants in the gap junction beta-2 (GJB2) gene may lead to various degrees of syndromic hearing loss (SHL) which is manifest as sensorineural hearing impairment and hyperproliferative epidermal disorders, including palmoplantar keratoderma with deafness (PPKDFN). So far, only a few GJB2 dominant variants causing PPKDFN have been discovered. Through the whole-exome sequencing (WES), a Chinese female patient with severe palmoplantar hyperkeratosis and delayed-onset hearing loss has been identified. She had a novel heterozygous variant, c.224G>C (p.R75P), in the GJB2 gene, which was unreported previously. The proband’s mother who had a mild phenotype was suggested the possibility of mosaicism by WES (∼120×), and the ultra-deep targeted sequencing (∼20,000×) was used for detecting low-level mosaic variants which provided accurate recurrence-risk estimates and genetic counseling. In addition, the analysis of protein structure indicated that the structural stability and permeability of the connexin 26 (Cx26) gap junction channel may be disrupted by the p.R75P variant. Through retrospective analysis, it is detected that the junction of extracellular region-1 (EC1) and transmembrane region-2 (TM2) is a variant hotspot for PPKDFN, such as p.R75. Our report reflects the important and effective diagnostic role of WES in PPKDFN and low-level mosaicism, expands the spectrum of the GJB2 variant, and furthermore provides strong proof about the relevance between the p.R75P variant in GJB2 and PPKDFN

Biliary Neuroendocrine Neoplasms: Clinical Profiles, Management, and Analysis of Prognostic Factors

Biliary neuroendocrine neoplasms (NENs) represent <1% of all NENs. The aim of this retrospective study is to present the clinical characteristics, management and prognosis profiles of 28 biliary NEN patients from a large tertiary center, and identify factors related to prognosis. Nine tumors originated from the gallbladder, two from the extrahepatic bile duct and 17 from the ampulla of Vater. One patient was classified as neuroendocrine tumor (NET) Grade 1, three patients were classified as NET Grade 2, 18 were graded neuroendocrine carcinoma (NEC) Grade 3 and six were classified as mixed adenoneuroendocrine carcinoma (MANEC). The overall survival rate and disease-free survival rate did not have statistically significant differences between tumors of different locations or different grading. Recurrence of disease correlated with poor prognosis (p < 0.001). Lymphovascular invasion and invasion beyond the submucosa were related to higher risk of local lymph node metastases. Multivariate analysis identified patient age (p = 0.021) and R0 resection margin (p = 0.027) as independent prognostic factors associated with overall survival. Our study included relatively large numbers of biliary tract NENs with intact follow-up information. Patients with biliary neuroendocrine tumors showed different clinical outcomes according to tumor locations and tumor grades. Achieving R0 resection is important for better prognosis

Decoupling of economic growth and emissions in China’s cities: A case study of the Central Plains urban agglomeration

Recently, the economy has grown rapidly in China’s Central Plains urban agglomeration, with high energy consumption and a huge pressure on reducing CO2 emissions. Thus, low-carbon development is an important measure to solve economic, energy and environmental problems. To analyse low-emission development, this paper clarifies the evolutionary characteristics of CO2 emissions and the decoupling relationship between GDP and CO2 emissions based on the latest available data from 2000 to 2015. The results indicate that CO2 emissions of Pingdingshan and Changzhi are higher in the same year. The ratios from coal consumption accounting for the total CO2 emissions are clearly bigger than from other energy types and industrial processes. Changzhi, Luoyang and Pingdingshan have reached their peaks. Five cities have experienced strong decoupling after 2010, 13 cities present weak decoupling, 4 cities present growth connection, and 7 cities show growth negative decoupling. It can be concluded that a relatively smaller proportion of industry and strict policy implementations of coal reduction are the main factors in inhibiting the decoupling. So the proportion of coal purification should be increased firstly. Then, the energy consumption structure should be changed from the traditional coal consumption structure to coal, oil and gas. Lastly, economic means can be used to control CO2 emissions