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ObjectiveTo evaluate the clinical efficacy and safety of Notoginseng Radix et Rhizoma powder in treating dyslipidemia by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodSixty patients with dyslipidemia (syndrome of combined phlegm and stasis) treated in the Third Affiliated Hospital of Henan University of Chinese Medicine from May 2021 to June 2022 were selected in this study and randomized into two groups according to the randomized, double-blind control principle. The control group was treated with Xuezhikang capsules + Notoginseng Radix et Rhizoma powder placebo and the observation group with Notoginseng Radix et Rhizoma powder + Xuezhikang capsules placebo for 6 weeks. The clinical efficacy, traditional Chinese Medicine (TCM) syndrome scores, and liver and kidney function indicators were evaluated at weeks 0, 3, and 6. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the expression of vascular endothelial growth factor (VEGF), kinase insert domain receptor (KDR), epidermal growth factor (EGF), and epidermal growth factor receptor (EGFR) in the peripheral serum. Quantitative Real-time PCR was employed to measure the mRNA levels of KDR, EGFR, PI3K, and Akt in the mononuclear cells of the peripheral blood. ResultThe observation group (83.33%) showed the total effective rate comparable to that of the control group (89.66%) and no adverse reactions. Compared with before treatment, the patients in the observation group showed decreased TCM syndrome score and serum levels total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) and after being treated for 3 and 6 weeks (P<0.05), the level of high-density lipoprotein cholesterol (HDL-C) showed an upward trend, but the difference was not statistically significant. After treatment, the two groups showed no significant differences. Compared with that before treatment, the mRNA expression of PI3K, Akt and EGFR in peripheral blood mononuclear cell and the expression of EGF, VEGF and KDR in serum of the observation group showed a downward trend with time, in which the mRNA expression of PI3K, Akt, VEGF and KDR decreased more significantly (P<0.05),The expression levels of KDR mRNA and serum EGFR show a trend of first increasing and then decreasing.Compared with the control group after treatment, there was no statistically significant difference in mRNA expression of PI3K, Akt, EGFR, and KDR, as well as serum levels of EGF, EGFR, VEGF, and KDR between the two groups of patients at the same time point. ConclusionNotoginseng Radix et Rhizoma powder is safe and effective in correcting dyslipidemia. It may inhibit the PI3K/Akt signaling pathway by down-regulating the expression of VEGF/KDR to lower the blood lipid level.
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OBJECTIVE To study protective effect and potential mechanism of Modified yupingfeng nasal spray (YPF+) on nasal mucosal injury in allergic rhinitis (AR) model rats. METHODS AR model was induced by ovalbumin (OVA) and randomly divided into model group, YPF+group (50 µg/side,twice a day), positive control group (Mometasone furoate aqueous nasal spray, 50 µg/side,once a day); the blank group was set up, with 10 rats in each group. Administration groups were given relevant medicine, and blank group and model group were given equivalent normal saline for consecutive 4 weeks. Thirty minutes after last medication, the behavioral scores of rats were recorded, and the pathological changes of their nasal mucosa tissue were observed. The level of reactive oxygen species (ROS) in nasal mucosa tissue was detected. The protein and mRNA expressions of nucleotide- binding oligomerization domain-like receptor protein 3 (NLRP3),caspase-1,gasdermin D (GSDMD) were detected; the contents of interleukin-1β (IL-1β) and IL-18 in serum were also determined. RESULTS Compared with blank group, in model group, the nasal mucosa tissue structure was disordered, inflammatory cells infiltrated seriously, and lamina propria vascular dilation was visible; its behavioral score and pathological score, the level of ROS, protein and mRNA expressions of NLRP3, caspase-1 and GSDMD, serum contents of IL-1β and IL-18 in nasal mucosa tissue were increased significantly (P<0.05). Compared with model group, the symptoms of nasal mucosal injury in rats of each drug group were improved to varying degrees, and the above indicators were significantly reduced (P<0.05). CONCLUSIONS YPF+ may improve nasal mucosal injury of rats, relieve AR symptoms such as sneezing, itchy nose, runny nose, the mechanism of which may be associated with reducing the production of ROS in nasal mucosa and downregulating NLRP3/caspase-1/ GSDMD pathway.
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OBJECTIVES@#To explore a new method for electroencephalography (EEG) background analysis in neonates with hypoxic-ischemic encephalopathy (HIE) and its relationship with clinical grading and head magnetic resonance imaging (MRI) grading.@*METHODS@#A retrospective analysis was performed for the video electroencephalography (vEEG) and amplitude-integrated electroencephalography (aEEG) monitoring data within 24 hours after birth of neonates diagnosed with HIE from January 2016 to August 2022. All items of EEG background analysis were enrolled into an assessment system and were scored according to severity to obtain the total EEG score. The correlations of total EEG score with total MRI score and total Sarnat score (TSS, used to evaluate clinical gradings) were analyzed by Spearman correlation analysis. The total EEG score was compared among the neonates with different clinical gradings and among the neonates with different head MRI gradings. The receiver operating characteristic (ROC) curve and the area under thecurve (AUC) were used to evaluate the value of total EEG score in diagnosing moderate/severe head MRI abnormalities and clinical moderate/severe HIE, which was then compared with the aEEG grading method.@*RESULTS@#A total of 50 neonates with HIE were included. The total EEG score was positively correlated with the total head MRI score and TSS (rs=0.840 and 0.611 respectively, P<0.001). There were significant differences in the total EEG score between different clinical grading groups and different head MRI grading groups (P<0.05). The total EEG score and the aEEG grading method had an AUC of 0.936 and 0.617 respectively in judging moderate/severe head MRI abnormalities (P<0.01) and an AUC of 0.887 and 0.796 respectively in judging clinical moderate/severe HIE (P>0.05). The total EEG scores of ≤6 points, 7-13 points, and ≥14 points were defined as mild, moderate, and severe EEG abnormalities respectively, which had the best consistency with clinical grading and head MRI grading (P<0.05).@*CONCLUSIONS@#The new EEG background scoring method can quantitatively reflect the severity of brain injury and can be used for the judgment of brain function in neonates with HIE.
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Infant, Newborn , Humans , Hypoxia-Ischemia, Brain/diagnostic imaging , Retrospective Studies , Brain Injuries , Electroencephalography , ROC CurveABSTRACT
OBJECTIVES@#Gastrointestinal endoscopy plays an important role in the diagnosis and treatment of gastrointestinal diseases. The satisfaction degree of gastrointestinal endoscopy can directly affect the patient's compliance and further impact the treating effect. At present, there is no scale to evaluate the satisfaction degree of gastrointestinal endoscopy in China. This study aims to develop a satisfaction scale of gastrointestinal endoscopy suitable for national conditions and to evaluate its reliability and validity, which provides a tool for clinic to evaluate patients' satisfaction with gastrointestinal endoscopy.@*METHODS@#The original gastrointestinal endoscopy satisfaction scale was compiled by literature review, consulting senior endoscopists and experts. Through the first round of survey about 120 patients, the original scale was analyzed and modified according to the results to get the gastrointestinal endoscopy satisfaction scale (formal scale). The formal scale was used to conduct the second round of survey about 200 patients. The reliability and validity of the scale were analyzed and evaluated according to the survey results.@*RESULTS@#The reliability of the original scale was good but the validity was poor. The formal scale had 2 dimensions and 10 items, the Cronbach's alpha and split-half reliability were 0.889 and 0.823. The structure validity index χ2/df was 2.513, root mean square error of approximation (RMSEA) was 0.094, goodness of fit index (GFI) was 0.914, adjusted goodness of fit index (AGFI) was 0.861, comparative fit index (CFI) was 0.946, normed fit index (NFI) was 0.915. The aggregate validity was general, the discriminative validity was good, and the direct score of patients was strongly correlated with the total score of the scale.@*CONCLUSIONS@#The gastrointestinal endoscopy satisfaction scale has good reliability and validity, which can be used as a tool to evaluate patients' satisfaction with gastrointestinal endoscopy in China.
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Humans , Reproducibility of Results , China , Endoscopy, Gastrointestinal , Patient Compliance , Personal SatisfactionABSTRACT
Strigolactones(SLs) are a class of sesquiterpenoids derived from the carotenoid biosynthesis pathway with the core carbon skeleton consisting of tricyclic lactone(ABC tricyclic ring) and α,β-unsaturated furan ring(D ring). SLs are widely distributed in higher plants and are symbiotic signals between plants and Arbuscular mycorrhiza(AM), which play key roles in the evolution of plant colonizing terrestrial habitats. As a new type of plant hormone, SLs possess such important biological functions as inhibiting shoot branching(tillers), regulating root architecture, promoting secondary growth, and improving plant stress resistance. Therefore, SLs have attracted wide attention. The biological functions of SLs are not only closely related to the formation of "excellent shape and quality" of Chinese medicinal materials but also have important practical significance for the production of high-quality medicinal materials. However, SLs have been currently widely studied in model plants and crops such as Oryza sativa and Arabidopsis thaliana, and few related studies have been reported on SLs in medicinal plants, which need to be strengthened. This review focused on the latest research progress in the isolation and identification, biological and artificial synthesis pathways, biosynthesis sites and transport modes, signal transduction pathways and mechanisms, and biological functions of SLs, and prospected the research on the regulation mechanism of SLs in the growth and development of medicinal plants and their related application on targeted regulation of Chinese herbal medicine production, which is expected to provide some references for the in-depth research on SLs in the field of Chinese medicinal resources.
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Arabidopsis , Lactones , Plants, MedicinalABSTRACT
Vascular access devices are regarded as double-edged swords since being used as lifesaving accesses widely as well as causing vessel catheter associated infections and other complications.In severe cases, it may even endanger life. This paper expounded the importance and necessity of vessel catheter associated infections prevention and control from several aspects such as national policy promotion, medical insurance payment innovation and clinical management demand, analyzed the key links of vessel catheter associated infections prevention and control and the research status quo here and abroad based on the life cycle of the catheter, and pondered the future directions considering the current difficulties and blind spots.
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OBJECTIVE@#To explore the genotyping characteristics of human fecal Escherichia coli( E. coli) and the relationships between antibiotic resistance genes (ARGs) and multidrug resistance (MDR) of E. coli in Miyun District, Beijing, an area with high incidence of infectious diarrheal cases but no related data.@*METHODS@#Over a period of 3 years, 94 E. coli strains were isolated from fecal samples collected from Miyun District Hospital, a surveillance hospital of the National Pathogen Identification Network. The antibiotic susceptibility of the isolates was determined by the broth microdilution method. ARGs, multilocus sequence typing (MLST), and polymorphism trees were analyzed using whole-genome sequencing data (WGS).@*RESULTS@#This study revealed that 68.09% of the isolates had MDR, prevalent and distributed in different clades, with a relatively high rate and low pathogenicity. There was no difference in MDR between the diarrheal (49/70) and healthy groups (15/24).@*CONCLUSION@#We developed a random forest (RF) prediction model of TEM.1 + baeR + mphA + mphB + QnrS1 + AAC.3-IId to identify MDR status, highlighting its potential for early resistance identification. The causes of MDR are likely mobile units transmitting the ARGs. In the future, we will continue to strengthen the monitoring of ARGs and MDR, and increase the number of strains to further verify the accuracy of the MDR markers.
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Humans , Escherichia coli/genetics , Escherichia coli Infections/epidemiology , Multilocus Sequence Typing , Genotype , Beijing , Drug Resistance, Multiple, Bacterial/genetics , Anti-Bacterial Agents/pharmacology , Diarrhea , Microbial Sensitivity TestsABSTRACT
Objective:To learn about the status of iodine deficiency disorders (IDD) in Zhumadian City, Henan Province, and to provide basis for scientific intervention measures.Methods:From 2016 to 2020, monitoring sites were set up in nine counties (districts) of Zhumadian City, and a town/street was selected from each of the five directions of East, West, South, North and Middle at each monitoring site. One primary school was selected from each town/street, 40 non-boarding children aged 8-10 years were selected from each primary school (half male and half female). In addition, 20 pregnant women were selected from each town/street. Urine samples and edible salt samples at home were collected from these children and pregnant women for iodine determination. Some children and pregnant women were selected to investigate the awareness rate of IDD prevention and treatment knowledge. Thyroid B-ultrasound examination was performed in some children. Iodine in drinking water was determined according to the national and provincial requirements of "strengthening scientific iodine supplementation".Results:From 2016 to 2020, a total of 13 500 salt samples were tested, including 12 453 qualified iodized salt samples and 246 non-iodized salt samples. The qualified iodized salt consumption rates of children and pregnant women were 92.26% (8 303/9 000) and 92.22% (4 150/4 500), respectively, and the non iodized salt consumption rates were 1.89% (170/9 000) and 1.69% (76/4 500), respectively. The median urinary iodine concentration of children were 208.91, 179.02, 222.85, 203.50 and 230.50 μg/L, respectively. The median urinary iodine concentration of pregnant women were 182.01, 153.26, 178.72, 196.82 and 178.75 μg/L, respectively. The goiter rate in children was 1.63% (49/3 000), there was no significant difference between different age groups (χ 2 = 0.47, P = 0.790), and between different genders (χ 2 = 0.01, P = 0.912). The awareness rate of IDD prevention and treatment knowledge was 94.68% (11 916/12 585) in children and 91.75% (4 537/4 945) in pregnant women. A total of 27 664 water samples were collected from 1 572 administrative villages, with a median of 12.90 μg/L of water iodine, including 1 383 low-iodine villages, 173 moderately iodine villages and 16 high-iodine villages. Conclusions:Children's iodine nutrition exceeds the appropriate amount, and pregnant women's iodine nutrition is appropriate in Zhumadian City Henan Province. In combination with the results of water iodine monitoring, we will continue to carry out IDD monitoring and consolidate the results of prevention and control.
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Antibody-mediated rejection (AMR) is one of the major causes of graft loss after transplantation. Recently, the regulation of B cell differentiation and the prevention of donor-specific antibody (DSA) production have gained increased attention in transplant research. Herein, we established a secondary allogeneic in vivo skin transplant model to study the effects of romidepsin (FK228) on DSA. The survival of grafted skins was monitored daily. The serum levels of DSA and the number of relevant immunocytes in the recipient spleens were evaluated by flow cytometry. Then, we isolated and purified B cells from B6 mouse spleens in vitro by magnetic bead sorting. The B cells were cultured with interleukin-4 (IL-4) and anti-clusters of differentiation 40 (CD40) antibody with or without FK228 treatment. The immunoglobulin G1 (IgG1) and IgM levels in the supernatant were evaluated by enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were conducted to determine the corresponding levels of messenger RNA (mRNA) and protein expression in cultured cells and the recipient spleens. The results showed that FK228 significantly improved the survival of allogeneic skin grafts. Moreover, FK228 inhibited DSA production in the serum along with the suppression of histone deacetylase 1 (HADC1) and HDAC2 and the upregulation of the acetylation of histones H2A and H3. It also inhibited the differentiation of B cells to plasma cells, decreased the transcription of positive regulatory domain-containing 1 (Prdm1) and X-box-binding protein 1 (Xbp1), and decreased the expression of phosphorylated inositol-requiring enzyme 1 α (p-IRE1α), XBP1, and B lymphocyte-induced maturation protein-1 (Blimp-1). In conclusion, FK228 could decrease the production of antibodies by B cells via inhibition of the IRE1α-XBP1 signaling pathway. Thus, FK228 is considered as a promising therapeutic agent for the clinical treatment of AMR.
Subject(s)
Animals , Mice , Depsipeptides , Endoribonucleases , Hematopoietic Stem Cell Transplantation , Histone Deacetylase Inhibitors/pharmacology , Protein Serine-Threonine Kinases , Skin TransplantationABSTRACT
Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04±0.65 vs. 0.99±0.09, F=30.36, P<0.001), and was closely related to T stage and clinical stage (Ⅰ-Ⅱvs.Ⅲ-Ⅳ: 1.75±0.39 vs. 2.18±0.71, F=2.25, P<0.05; T1-2 vs. T3-4: 1.71±0.42 vs. 2.20±0.69, F=2.06, P<0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P<0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Exosomes , Ferroptosis , Head and Neck Neoplasms , Macrophages , Squamous Cell Carcinoma of Head and NeckABSTRACT
The morbidity of inflammatory bowel diseases (IBD) is rising rapidly but no curative therapies to prevent its recurrence. Cell death is crucial to maintaining homeostasis. Necroptosis is a newly identified programmed cell death and its roles played in IBD need to be explored. Necroptosis is mediated by receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL), which resulted in cell swelling, plasma membrane rupture, intracellular content leaking, and eventually cell death as well as the promotion of inflammation. Studies have found that inhibiting necroptosis alleviated IBD in animal models and IBD patients with an increased level of necroptosis in inflammatory tissues, indicating that necroptosis is related to the pathogenesis of IBD. However, due to the complexity in regulation of necroptosis and the involvement of multiple functions of relevant signaling molecules, the specific mechanism remains elusive. Necroptosis may play a vital regulatory role in the pathogenesis of IBD, which provides a new idea and method for further exploring the therapeutic target of IBD.
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SUMMARY: Coreopsis tinctoria Nutt. (C. tinctoria Nutt.) can protect diabetic kidneys, but the mechanisms are unclear. This work is to investigate the potential mechanisms of C. tinctoria Nutt. in the treatment of diabetic nephropathy based on network pharmacology analysis of its active ingredients. Twelve small molecular compounds of C. tinctoria Nutt. and targets related to diabetic nephropathy were docked by Discovery Studio 3.0. DAVID database was used for GO enrichment and KEGG pathway analysis. Cytoscape 3.6.1 was used to construct active ingredient-target network. Cell viability was detected with MTT. Glucose consumption was analyzed with glucose oxidase method. Protein expression was measured with Western blot and immunofluorescence. Electron microscopy observed autophagosomes. The core active ingredients of C. tinctoria Nutt. included heriguard, flavanomarein, maritimein, and marein. Twenty-one core targets of the 43 potential targets were PYGM, TLR2, RAF1, PRKAA2, GPR119, INS, CSF2, TNF, IAPP, AKR1B1, GSK3B, SYK, NFKB2, ESR2, CDK2, FGFR1, HTRA1, AMY2A, CAMK4, GCK, and ABL2. These 21 core targets were significantly enriched in 50 signaling pathways. Thirty- four signaling pathways were closely related to diabetic nephropathy, of which the top pathways were PI3K/AKT, insulin, and mTOR, and insulin resistance. The enriched GO terms included biological processes of protein phosphorylation, and the positive regulation of PI3K signaling and cytokine secretion; cellular components of cytosol, extracellular region, and extracellular space; and molecular function of protein kinase activity, ATP binding, and non-membrane spanning protein tyrosine kinase activity. In vitro experiments found that marein increased the expression of phosphorylated AKT/AKT in human renal glomerular endothelial cells of an insulin resistance model induced by high glucose, as well as increased and decreased, respectively, the levels of the microtubule-associated proteins, LC3 and P62. C. tinctoria Nutt. has many active ingredients, with main ingredients of heriguard, flavanomarein, maritimein, and marein, and may exert anti-diabetic nephropathy effect through various signaling pathways and targets.
RESUMEN: Coreopsis tinctoria Nutt. (C. tinctoria Nutt.) puede proteger riñones diabéticos, sin embargo los mecanismos son desconocidos. Este trabajo se realizó para investigar los potenciales mecanismos de C. tinctoria Nutt. en el tratamiento de la nefropatía diabética basado en el análisis de farmacología en red de sus principios activos. Doce compuestos moleculares pequeños de C. tinctoria Nutt. y los objetivos relacionados con la nefropatía diabética fueron acoplados por Discovery Studio 3.0. La base de datos DAVID se utilizó para el enriquecimiento GO y el análisis de la vía KEGG. Se usó Cytoscape 3.6.1 para construir una red de ingrediente-objetivo activa. La viabili- dad celular se detectó mediante MTT. El consumo de glucosa se analizó con el método de glucosa oxidasa. La expresión proteica fue determinada mediante Western blot e inmunofluorescencia. En la microscopía electrónica se observó autofagosomas. Los principales ingredientes activos de C. tinctoria Nutt. incluyeron heriguard, flavanomarein, maritimin y marein. Veintiún de los 43 objetivos potenciales fueron PYGM, TLR2, RAF1, PRKAA2, GPR119, INS, CSF2, TNF, IAPP, AKR1B1, GSK3B, SYK, NFKB2, ESR2, CDK2, FGFR1, HTRA1, AMY2A, CAMK4, GCK y ABL2. Estos 21 objetivos principales se enriquecieron significativamente en 50 vías de señalización. Treinta y cuatro vías de señalización estuvieron estrechamente relacionadas con la nefropatía diabética, de las cuales las principales vías fueron PI3K/ AKT, insulina y mTOR, y resistencia a la insulina. Los términos GO enriquecidos incluyeron procesos biológicos de fosforilación proteica, la regulación positiva de la señalización de PI3K y la secreción de citoquinas; componentes celulares del citosol, región extracelular y espacio extracelular; y la función molecular de la actividad de la proteína quinasa, la unión de ATP y la actividad de la proteína tirosina quinasa que no se extiende por la membrana. Los experimentos in vitro encontraron que la mareína aumentaba la expresión de AKT/AKT fosforilada en células endoteliales glomerulares renales humanas en un modelo de resistencia a la insulina inducida por niveles elevados de glucosa, así como aumentaron y disminuyeron respectivamente, los niveles de las proteínas asociadas a los microtúbulos, LC3 y P62. C. tinctoria Nutt. tiene muchos principios activos, con ingredientes principales de heriguard, flavanomarein, maritimain y marein, y puede ejercer un efecto de nefropatía antidiabética a través de distintass vías de señalización y objetivos.
Subject(s)
Coreopsis/chemistry , Diabetic Nephropathies , Network Pharmacology , Microscopy, Electron , Blotting, Western , Fluorescent Antibody Technique , ChalconesABSTRACT
SUMMARY: Marein is the main active substance of Coreopsis tinctoria nutt. It not only has anti-oxidation and anti-tumor effects, but also can lower blood lipid, prevent high blood glucose, improve insulin resistance, inhibit gluconeogenesis and promote glycogen synthesis. However, the exact mechanism of its action is still unclear. Here, we explored the effect and mechanism of Marein on insulin resistance. The mice were divided into db/m, db/db, metformin+db/db, and marein+db/db groups. The body weight and kidney weight were recorded. Serum biochemical and renal function tests were measured after 8 weeks of continuous administration. Kidney tissues were subjected to HE staining, PAS staining, and Masson staining. The effect of marein on PI3K/Akt signal and autophagy pathway was detected by Western blot. After 8 weeks of Marein intervention, the body weight and kidney weight of mice did not change significantly, but the fasting blood glucose and blood lipid levels were significantly reduced than db/db group. Marein significantly improved the insulin resistance index, increased serum adiponectin and improved glucose and lipid metabolism disorders of db/db mice. Moreover, marein improved the basement membrane thickness of glomeruli and tubules, improved glomerular sclerosis and tubular fibrosis, as well as renal insufficiency, thereby protecting kidney function and delaying the pathological damage. Furthermore, marein increased the expression of PI3K and the phosphorylation of Akt/Akt (Ser473), and promoted the expression of LC3II/I, Beclin1 and ATG5. Additionally, it promoted the expression of FGFR1 in the kidney of db/db mice, and promoted the increase of serum FGF21 and FGF23. Marein has a protective effect on the kidneys of diabetic mice. It protects diabetic nephropathy by regulating the IRS1/PI3K/Akt signaling pathway to improve insulin resistance. Therefore, marein may be an insulin sensitizer.
RESUMEN: Marein es la principal sustancia activa de Coreopsis tinctoria nutt. No solo tiene efectos antioxidantes y antitumorales, sino que también puede reducir los lípidos en sangre, prevenir la glucemia alta, mejorar la resistencia a la insulina, inhibir la gluconeogénesis y promover la síntesis de glucógeno. Sin embargo, el mecanismo exacto de su acción aún no está claro. Se analizó el efecto y el mecanismo de Marein sobre la resistencia a la insulina. Los ratones se dividieron en grupos db / m, db / db, metformina + db / db y mareína + db / db. Se registró el peso corporal y el peso de los riñones. Se midieron las pruebas de función renal y bioquímica sérica después de 8 semanas de administración continua. Los tejidos renales se sometieron a tinción HE, tinción PAS y tinción Masson. El efecto de la mareína sobre la señal de PI3K / Akt y la vía de autofagia se detectó mediante Western blot. Al término de 8 semanas de tratamiento con mareína, el peso corporal y el peso de los riñones de los ratones no cambiaron significativamente, pero los niveles de glucosa en sangre y lípidos en sangre en ayunas se redujeron significativamente en relación a los del grupo db / db. Marein mejoró significativamente el índice de resistencia a la insulina, aumentó la adiponectina sérica y mejoró los trastornos del metabolismo de la glucosa y los lípidos de los ratones db / db. Además, la mareína mejoró el grosor de la membrana basal de los glomérulos y túbulos, mejoró la esclerosis glomerular y la fibrosis tubular, así como la insuficiencia renal, protegiendo la función renal y retrasando el daño patológico. Además, la mareína aumentó la expresión de PI3K y la fosforilación de Akt / Akt (Ser473), y promovió la expresión de LC3II / I, Beclin1 y ATG5. Además, promovió la expresión de FGFR1 en el riñón de ratones db / db y el aumento de FGF21 y FGF23 en suero. Marein tiene un efecto protector sobre los riñones de ratones diabéticos. Protege la nefropatía diabética regulando la vía de señalización IRS1 / PI3K / Akt para mejorar la resistencia a la insulina. Por tanto, la mareína puede ser un sensibilizador a la insulina.
Subject(s)
Animals , Mice , Insulin Resistance , Chalcones/administration & dosage , Diabetic Nephropathies , Autophagy/drug effects , Blood Glucose , Body Weight/drug effects , Immunohistochemistry , Blotting, Western , Lipids/bloodABSTRACT
Objective:To investigate the construction and application of telemedicine system in Tibet Autonomous Region.Methods:From June to July 2020, medical institutions at all levels in Tibet Autonomous Region were visited. Relevant information was collected through discussion, questionnaires and field visits, and the data of effective questionnaires were statistically analyzed.Results:A total of 125 medical institutions were visited, covering 7 regions of Tibet Autonomous Region, of which 74 medical institutions were able to realize audio-video two-way communication with the telemedicine platform of the PLA General Hospital. Seventy-three valid questionnaires were collected, and 64(88%)hospitals had software or hardware audio and video terminals. Twenty-five hospitals had never carried out remote consultation, accounting for 34%. The annual remote consultation amount of 35 hospitals was less than 10 cases, and that of 11 hospitals was 11-100 cases. Only 2 hospitals had carried out remote ECG and remote ultrasound diagnosis, with an annual consultation volume of more than 100 cases.Conclusions:The hospitals at or above the county level in Tibet Autonomous Region have established telemedicine system, but there are few remote services, the system idle rate is high, and the distance education resources are not matched.
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In the trends of large-scale brain research projects around the world, the China Brain Project aims to promote the understanding of the basic principles of the brain, and use the basic research of neuroscience to serve some urgent social and economic needs at the same time.As we approach the launch of this effort aimed at revolutionizing our understanding of cognitive principles of the brain, early diagnoses of brain diseases and brain-like intelligence technologies, it is timely to review the new progress in recent international brain research projects, and the deployment and future trajectory of neuroscience research in China.
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@#Objective To investigate the value of chest high-resolution computed tomography (HRCT) score in evaluating the severity of hip fracture-induced early acute lung injury (ALI) in the elderly patients. Methods The clinical data of 289 elderly hip fracture patients in Chongqing Traditional Chinese Medicine Hospital from July 2014 to April 2020 were retrospectively analyzed. All patients were divided into two groups, including an ALI group (n=114, 36 males and 78 females at age of 82.94±6.85 years) and a non-ALI group (n=175, 51 males and 124 females at age of 84.42±6.31 years). General information, chest HRCT scores and PaO2/FiO2 were compared between the two groups. Correlation analysis was used to compare the relationship between chest HRCT scores and PaO2/FiO2. Multiple linear stepwise regression analysis was applied to evaluate the effective extent of the diffuse ground glass opacity (DGGO), intense parenchymal opacification (IPO), and reticulation HRCT scores to the overall HRCT scores. Results The DGGO scores, IPO scores, reticulation scores, overall HRCT scores and PaO2/FiO2 were higher in the ALI group than those in the non-ALI group (P<0.001). In the ALI group, correlation analysis showed that DGGO, overall HRCT scores were in significantly negative correlation with PaO2/FiO2 (P<0.001). In addition, the correlation among PaO2/FiO2 and overall HRCT scores was more significant than that of DGGO scores. Multiple stepwise regression analysis indicated that DGGO, IPO, and reticulation scores were independent influencing factors for overall HRCT scores. Among the influencing factors, DGGO scores had the greatest impact, then IPO scores and reticulation scores. The HRCT signs of DGGO, IPO, and reticulation appeared simultaneously had the greatest effects on the overall HRCT scores. Conclusion The chest HRCT score, which is associated with PaO2/FiO2, also can be used in the severity assessment of elderly patients with early ALI caused by hip fracture.
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OBJECTIVE@#Discuss the working ideas of the dynamic adjustment mechanism of medical device classification in the United States, and provide reference for the construction of medical device related mechanisms in China.@*METHODS@#Collect and interpret the documents of regulatory background, procedures and orders of the dynamic adjustment mechanism of the medical device classification in the United States, and summarize the overall situation and specific cases of the medical device classification adjustment under this mechanism in recent years.@*RESULTS@#The US work idea of the medical device classification dynamic adjustment mechanism is based on the latest valid scientific evidence, conducting risk analysis and identification, and determining the corresponding measures.@*CONCLUSIONS@#During the adjustment process, industry stakeholders have repeatedly discussed and achieved final agreement. Its procedures and working ideas can be used as a reference for China's work.
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China , United States , United States Food and Drug AdministrationABSTRACT
Objective:To observe the effect of Dingkundan in adjuvant treatment of clinical symptoms, quality of life, immune function and prognosis of patients with radiotherapy and chemotherapy after endometrial carcinoma (EC) operation. Method:Patients were divided into control group (82 cases) and observation group (86 cases) according to random number table. A total of 75 patients in control group completed the study (4 patients fell off or lose visit, and 3 patients were eliminated), while 77 patients in observation group completed the study (5 patients fell off or lose visit, and 4 patients were deleted). After operation, patients got brachytherapy, external pelvic irradiation and chemotherapy. Patients in control group got Bazhenwan, 1 pill/time, 2 times/day, and those in observation group got Dingkundan, 7 g/time, 2 times/day. The course of treatment lasted for 4 months, and long-time follow-up data was recorded. Before treatment, and at the second and fourth month after treatment, deficiency of Qi and blood was scored. Toxic reactions after radiotherapy and chemotherapy were recorded, and incidence rate of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level were compared. And levels of T lymphocyte subsets (CD3<sup>+</sup>, CD4<sup>+</sup>, CD8<sup>+</sup> and CD4<sup>+</sup>/CD8<sup>+</sup>) were detected, European collaborative quality of life Cancer Core Scale (EORTC QLQ-C30) was evaluated, and expressions of pce125 (CA125), epididymis protein 4 (HE4), Dickkopf-related protein-1 (DKK1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and transforming growth factor-<italic>β</italic><sub>1</sub> (TGF-<italic>β</italic><sub>1</sub>) were tested before and after treatment. The follow-up was made for every three months, and the progression (recurrence/metastasis) of patients was recorded. Result:Scores of deficiency of Qi and blood in observation group were lower than those in control group at the second and fourth week after treatment (<italic>P</italic><0.01). Incidence rates of acute and advanced radiation injury of bladder and rectum and toxicity of chemotherapeutic drugs at grade 3 or above grade 3 level and incidence rates of bone marrow suppression, gastrointestinal toxicity, neurotoxicity were lower than those in control group (<italic>P</italic><0.05). Five functional dimensions and overall quality of life score based on EORTC and QLQ-C30 in observation group were higher than those in control group (<italic>P</italic><0.01), and scores of three symptom dimensions were lower than those in control group (<italic>P</italic><0.01). Levels of CD3<sup>+</sup>, CD4<sup>+</sup> and CD4<sup>+</sup>/CD8<sup>+</sup> were higher than those in the control group (<italic>P</italic><0.01), and CD8<sup>+</sup> was lower than those in the control group (<italic>P</italic><0.01). Levels of CA125, HE4, DKK1, VEGF, MMP-9 and TGF-<italic>β</italic><sub>1</sub> were lower than those in the control group (<italic>P</italic><0.01). The disease progression rate in observation group was 18.18% (14/77), which was lower than 33.33% (25/75) in control group (<italic>χ</italic><sup>2</sup>=4.572, <italic>P</italic><0.05). Conclusion:In adjuvant treatment of patients with radiotherapy and chemotherapy after EC operation, Dingkundan can reduce the symptoms of Qi and blood deficiency syndrome and side effects caused by radiotherapy and chemotherapy, improve the quality of life and immune function, inhibit the expression of tumor markers and tumor growth factor, delay the progression of tumor and improve the prognosis.
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OBJECTIVE@#To investigate the mechanisms underlying elemene-induced analgesia in rats with spared nerve injury (SNI).@*METHODS@#Sixty-five rats were equally divided into 5 groups using a random number table: naive group, sham group, SNI group, SNI + elemene (40 mg·kg@*RESULTS@#The SNI rat model exhibited a significant decrease in paw withdrawal threshold and exploratory behaviour in the EPM (P<0.05). Consecutive administration of elemene alleviated SNI-induced mechanical allodynia and anxiety in rats (P<0.05). Immunohistochemical data showed that elemene decreased SNI-induced upregulation of NDRG2 within the SDH (P<0.05). Double immunofluorescent staining data further showed that elemene decreased SNI-induced upregulation of the number of GFAP immunoreactive (-ir), NDRG-ir, and GFAP/NDRG2 double-labelled cells within the SDH (P<0.05). Immunoblotting data showed that elemene decreased SNI-induced upregulation of GFAP and NDRG2 within the SDH (P<0.05).@*CONCLUSION@#Elemene possibly alleviated neuropathic pain by downregulating the expression of NDRG2 in spinal astrocytes in a rat model of SNI.
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Animals , Rats , Astrocytes , Disease Models, Animal , Emulsions , Hyperalgesia/drug therapy , Nerve Tissue Proteins , Neuralgia/drug therapy , Rats, Sprague-Dawley , Sesquiterpenes , Spinal Cord , Spinal Cord Dorsal HornABSTRACT
Objective: To explore the role and mechanism of long non-coding RNA RP11-159K7.2 in the progression of sinonasal squamous cell carcinoma (SNSCC). Methods: Sixty-five cases of SNSCC tissues and adjacent tissues were selected from the Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University from 2009 to 2014. The expression of RP11-159K7.2 in SNSCC and adjacent tissues was detected by RNAscope in situ hybridization to observe its association with prognosis. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated proteins 9 (CRISPR/Cas9) was used to knockout the expression of RP11-159K7.2 in RPMI-2650 cells (SNSCC cell line). Cell counting kit-8 (CCK-8), wound healing and Transwell were performed to observe the changes of proliferation, migration and invasion of SNSCC cells in vitro after down-regulation of RP11-159K7.2. Moreover, the growth of xenograft in nude mice after down-regulation of RP11-159K7.2 was examined in vivo. Mechanically, the protein chip, Western blot and RNA immunoprecipitation were performed to identify the proteins bound by RP11-159K7.2. SPSS 17.0 was used for statistical analysis. Results: The expression of RP11-159K7.2 in SNSCC tissue was significantly higher than that in adjacent tissues. RP11-159K7.2 expression was closely related with T grade, nodal metastasis and differentiation of SNSCC (χ2 value was 4.697, 4.235 and 10.753, respectively, all P<0.05). The five-year survival rate of RP11-159K7.2 high expression patients was significantly lower than that of RP11-159K7.2 low expression ones (P=0.013 7). After the down-regulation of RP11-159K7.2, the proliferation, migration and invasion ability of SNSCC cells decreased significantly, and the growth of SNSCC xenograft was significantly inhibited. There were 31 candidate proteins that may bind to RP11-159K7.2. RP11-159K7.2 directly bound to nuclear factor-κB (NF-κB) in SNSCC cells, and the regulation of RP11-159K7.2 on the proliferation and invasion of SNSCC cells depended on NF-κB. Conclusion: The increased expression of RP11-159K7.2 in SNSCC may serve as a potential molecular marker for SNSCC prognosis assessment. It is currently considered that the carcinogenic mechanism of RP11-159K7.2 in SNSCC is related to the regulation of NF-κB protein.