Red blood cells(RBCs)are the primary mediators of oxygen transport in the human body,and their function is mainly achieved through conformational changes of hemoglobin(Hb).Hb is a tetramer composed of four subunits,with HbA being the predominant Hb in healthy adults,existing in two forms:tense state(T state)and relaxed state(R state).Endogenous regulators of Hb conformation include 2,3-diphosphoglyceric acid,carbon dioxide,protons,and chloride ions,while exogenous regulators include inositol hexaphosphate,inositol tripyrophosphate,benzabate,urea derivative L35,and vanillin,each with different mechanisms of action.The application of Hb conformational regulators provides new insights into the study of hypoxia oxygen supply issues and the treatment of sickle cell disease.

Endovascular stent implantation had become a major therapeutic option for heart,brain and peripheral vascular diseases.After stent implantation,CT angiography(CTA)and MR angiography(MRA)were often performed during follow-up to diagnose or predict relative complications as early as possible.The research progresses of different material endovascular stent and imaging follow-up after stent implantation were reviewed in this article.

Objective:Heme chloride(Hemin)is an in vitro purified form of natural heme and an important raw material for anti-anemia and antitumor drugs.This study aims to analyze the protective effect of Hemin on tissue damage in low-pressure oxygen chamber simulated plateau hypoxic mice,and explore its role in anti-plateau hypoxia. Methods:Thirty male BALB/c mice were randomly divided into a blank group,a positive drug group(acetazolomide,200 mg/kg),a Hemin low-dose group(15 mg/kg),a Hemin medium-dose group(30 mg/kg),and a Hemin high-dose group(60 mg/kg)with intraperitoneal injection.The anti-hypoxic activity of Hemin was explored by atmospheric closed hypoxia experiment and the optimal dose was screened.Thirty-six male BALB/c mice were randomly divided into a blank group,a hypoxia group,a positive drug group,and a Hemin high-dose group.The plasma inflammatory factor levels and oxidative stress indicators malondialdehyde(MDA),glutataione(GSH),and superoxide dismutase(SOD)levels of myocardium,brain,lung,and liver tissues were measured in different groups with hypoxia for 24 h.The degree of histopathological damage of mice was observed with HE staining.The degree of protection of Hemin against tissue hypoxia injury was detected with the hypoxia probe piperidazole. Results:Compared with the blank group,the survival time of mice in the positive drug group,the Hemin medium-dose group,and high-dose group was significantly extended(all P<0.05),with the highest prolongation rate in the Hemin high-dose group.Compared with the hypoxia group,mice in the Hemin high-dose group showed a significant increase in SOD level and GSH content of brain tissue,and a significant decrease in MDA content of lung tissue(all P<0.05).The results of HE staining and hypoxia probe showed that Hemin had a significant protective effect on the damage of liver,heart,brain and lung tissues of mice with hypoxia,and the most obvious effect on that of the brain tissue. Conclusion:Hemin has an effect of improvement on oxidative stress and inflammatory response caused by hypoxia,and has obvious protective effect on tissue damage caused by hypoxia.

Eukaryotic translation initiation factor 4B (eIF4B) plays an important role in mRNA translation initiation, cell survival and proliferation in vitro, but the in vivo function is poorly understood. In this study, via various experimental techniques such as hematoxylin-eosin (HE) staining, flow cytometry, Western blotting, and immunohistochemistry, we investigated the role of eIF4B in mouse embryo development using an eIF4B knockout (KO) mouse model and explored the mechanism. We found that the livers, but not lungs, brain, stomach, or pancreas, derived from eIF4B KO mouse embryos displayed severe pathological changes characterized by enhanced apoptosis and necrosis. Accordingly, high expression of cleaved-caspase 3, and excessive activation of mTOR signaling as evidenced by increased expression and phosphorylation of p70S6K and enhanced phosphorylation of 4EBP1, were observed in mouse embryonic fibroblasts and fetal livers from eIF4B KO mice. These results uncover a critical role of eIF4B in mouse embryo development and provide important insights into the biological functions of eIF4B in vivo.
Animals ; Apoptosis/genetics* ; Caspase 3 ; Eosine Yellowish-(YS) ; Eukaryotic Initiation Factors/metabolism* ; Fibroblasts ; Hematoxylin ; Liver/metabolism* ; Mice ; Ribosomal Protein S6 Kinases, 70-kDa/genetics* ; TOR Serine-Threonine Kinases

Areca catechu L. medicinal materials and their preparations are widely used in clinical practice. Betelnut polyphenol is one of the main chemical components with antioxidant, anti-inflammatory, and antibacterial effects. With continuous increase of high altitude activities, tissue oxidative damage caused by high altitude hypoxia seriously affects the ability to work, and the studies on anti-hypoxia drugs are particularly important. Recent studies have shown that betelnut polyphenols have protective effects on oxidative stress injury caused by hypoxia via improving blood gas index of hypoxic organism, increasing superoxide dismutase glutathione catalase activity, and scavenging excessive free radicals. The effects of betelnut polyphenols against hypoxia and oxidative damage protection suggest that betelnut polyphenols can be used as potential anti-hypoxia drugs and posses clinical prospects.
Antioxidants/pharmacology* ; Areca/chemistry* ; Humans ; Hypoxia ; Oxidative Stress ; Polyphenols/pharmacology* ; Superoxide Dismutase/metabolism*

Tibetan is a kind of medicine which extensively absorbed and fused the Chinese Traditional Medicine, Indian medicine and food through long-term practice and form the unique medical system. At the same time, the Qinghai Tibet plateau has characteristics of high altitude and lack of resources and oxygen, which has formed its unique geographical environment and grow a lot of rare medicinal plants. Tibetan medicine has a long history and is one of the relatively complete and influential ethnic medicines in China, which has played an important role in the treatment of plateau diseases. In recent years, with the increasing of economic activities in the plateau, the plateau anoxia had greatly affected the working capacity of the plateau. According to "Chinese medicine" through the literature, the pharmacological activities, active ingredients, growing environment of Tibetan medicine with good plateau hypoxia effect were reviewed and according to the site, which could be divided into the lung protection medicine, the cardiac protection medicine, the brain protection medicine, the liver protection medicine, the improvement of fatigue medicine and other medicine, which could provide theoretical basis for finding more potential anti-hypoxia drugs.

Objective:To establish rules for medical order review in parenteral nutrition, assist pharmacists in the efficient real-time pre-review of parenteral nutrition medical orders, and promote the standardized use of parenteral nutrition.Methods:Professional clinical nutrition pharmacists, prescription reviewing pharmacists, clinicians, and nutritionists jointly contributed to the formulation of custom prescription review rules for parenteral nutrition. Utilizing the prescription review system of our hospital, pharmacists reviewed and intervened parenteral nutrition medical orders in real time.Result:After the implementation of review rules, all of the medical orders for parenteral nutrition have been pre-reviewed in our hospital, and the related indicators that are out of normal range and the cases of single bottle infusion show significant reduction in frequency.Conclusion:The formulation and implementation of specific prescription review rules for parenteral nutrition can effectively assist pharmacists in real-time review of parenteral nutrition medical orders, and can solve the problems of inappropriate medical orders and single-bottle infusion.

Objective:To investigate the regulatory effects of sphingosine kinase-2 (SphK2) on the function of activated astrocytes and the progression of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:Primary mouse astrocytes were isolated from wild-type (WT) C57BL/6 mice and sphk2 gene knock-out ( sphk2 -/-) mice and stimulated in vitro with interleukin 17 (IL-17). Real-time PCR was used to measure the expression of inflammatory cytokines and chemokines at mRNA levels. Western blot and immunofluorescence were used to detect the expression of glial fibrillary acidic protein (GFAP) and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3). An EAE mouse model was constructed using myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) polypeptide. Western blot was used to detect the expression of GFAP and p-STAT3 at protein level and real-time PCR was used to detect the expression of inflammatory cytokines and chemokines at mRNA level in spinal cords. Hematoxylin-Eosin (HE) and Luxol fast blue (LFB) staining were used to observe the changes in inflammatory cell infiltration and demyelination in spinal cords. Results:Compared with the WT group, the phosphorylation of STAT3 was obviously reduced in in vitro activated mouse astrocytes of sphk2 -/- mice, and the expression of inflammatory cytokines and chemokines including monocyte chemotactic protein 1 (MCP-1), TNF-α and IL-6 at mRNA level was also significantly decreased. Compared with the WT EAE group, changes in the above-mentioned cytokines and relative proteins in sphk2 -/- EAE mice in vivo were similar to those in vitro. Moreover, inflammatory cell infiltration and demyelination were significantly reduced in spinal cords of sphk2 -/- EAE mice. However, no significant difference in in vitro or in vivo GFAP expression was observed between WT and sphk2 -/- mice. Conclusions:SphK2 might regulate the function of reactive astrocytes through STAT3 molecular pathway, thereby regulating the production of inflammatory cytokines and chemokines and participating in the pathological process of EAE.

Objective To explore the MRI findings of diffuse midline gliomas with H3K27M mutation, and help us understand this new entity and improve the accuracy of diagnosis. Methods The clinical and imaging data of 17 diffuse midline gliomas with H3K27M mutation confirmed by pathology were retrospectively collected from July 2016 to April 2018 in Guangdong Sanjiu Brain Hospital. All patients were performed with pre?contrast and post?contrast MRI examination. All images were analyzed according to the location, shape, boundary, solid or cystic, signal feature, enhancement feature, and degree of edema. Results (1) Location:Six cases located in thalamus,4 cases located in brainstem,1 located in hypothalamus, 6 cases had multiple lesions in the midline and/or involving one or more brain. (2) Morphology and boundary:Seven cases had regular shape and clear boundary, 10 cases had irregular shapes and unclear boundaries. (3) Necrosis, cystic degeneration, hemorrhage: Twelve cases had necrosis or cystic degeneration in varying degree, 4 cases had hemorrhage. (4) Signal and enhancement features: The solid component showed slightly?low or low signal on T1WI, and slightly?high or high signal on T2WI; the cystic component showed obvious low signal on T1WI and obvious high signal on T2WI. T1WI enhancement:Eight cases showed uneven light?moderate enhancements, and all cases were adults; Six cases showed significant enhancements with large or small rings; Three cases showed uneven obvious enhancement. (5) Peritumoral edema: Fourteen cases had mild peritumoral edema,1 case had moderate peritumoral edema,2 cases had obvious peritumoral edema. Conclusion The MRI findings of diffuse midline gliomas with H3K27M mutation had certain characteristics,which can help to improve the level of diagnosis and differential diagnosis.

Objective: Using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and microPET-CT to test the feasibility of ¹⁸F-FDG PET-CT for validation of olfactory function of rats with standard phenethyl alcohol (PEA) and isovaleric acid (IVA) odors stimulation. To verify the possibility of ¹⁸F-FDG PET-CT as a new objective examination method for olfactory function. Methods: Six healthy Sprague-Dawley (SD) male rats were selected with a weight of 250-300 g. First of all, buried food pellet test (BFT) was used to confirm the normal olfactory function of rats. Then in the next 3 days, after the intravenous injection of ¹⁸F-FDG (18 MBq/100 g), awaken rats were placed in a ventilated plexiglas cage for 30 min. Subsequently, pure air (the first day), PEA (the second day) and IVA (the third day) were delivered. After odor stimulation for 30 min, rats were performed by a static PET-CT under anesthesia. Images reconstructed were assessed by SPM method and analyzed by VBM method. Data was analysied by paired t test. Results: Activation regions of rat′s brain after PEA stimulation included bed nucleus and insula. Activation regions of rat′s brain after IVA stimulation included olfactory bulb, anterior olfactory nucleus, amygdala, entorhinal cortex, olfactory cortex, piriform cortex, insula, prefrontal cortex, cingulate cortex and bed nucleus (P<0.005, Ke>20 voxels). Conclusions Through microPET-CT, we can observe that olfactory stimulation with different odors can induce metabolic activation in different regions of rat′s brain, which was in concordance with olfactory regions. The olfactory related brain regions of rats have strong responses to odor stimulation of IVA.