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Objective To explore the efficacy and safety of evolocumab in elderly patients with high-risk cardiovascular diseases.Methods A total of 153 patients with poor lipid control after conventional statin therapy who were hospitalized in the cardiologic departments in the First,Sec-ond,Sixth and Eighth Medical Centers of Chinese PLA General Hospital from November 2019 to November 2022 were included,and divided into non-elderly group(<60 years old,46 cases),eld-erly group(60-74 years old,66 case)and very elderly group(≥75 years old,41 cases).They were all given evolocumab treatment according to guidelines.Another 50 over-75-year-old patients with high-risk cardiovascular diseases and poor lipid control who were hospitalized in the above cardiologic departments during the same period were treated with a statin drug combined with ezetimibe,and served as conventional treatment group(control group).The baseline clinical data and the blood indicators at 4th and 12th week after drug administration,and the occurrence of ad-verse drug reactions and major adverse cardiovascular events(MACE)within 12 weeks were com-pared among the groups.Results The levels of LDL-C and TC were significantly decreased in the three evolocumab treatment groups at 4 and 12 weeks after medication when compared with the baseline values(P<0.05,P<0.01),but there were no obvious differences in the 2 levels among the 3 groups at 12 weeks(P>0.05).At the time point,no statistical difference was observed in the incidence of adverse events in the three groups(2.2%vs 3.0%vs 2.4%,P>0.05).The levels of LDL-C and TC were decreased significantly in the very elderly group and the conventional treatment group at the 12th week when compared with the baseline levels(P<0.05,P<0.01),and the LDL-C level at the week was notably lower in the very elderly group than the convention-al treatment group(1.36±0.44 mmol/L vs 1.87±0.56 mmol/L,P<0.01).But no difference was seen in the incidence of MACE between the 2 groups(12.2%vs 16.0%,P>0.05),either in sur-vival rate between them(P=0.576).Conclusion For patients of all ages,evolocumab has good short-term efficacy in lipid control,and for those over 75 years old,the drug also shows good effi-cacy and sound safety.
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In South Asia, annual land use and land cover (LULC) is a severe issue in the field of earth science because it affects regional climate, global warming, and human activities. Therefore, it is vitally essential to obtain correct information on the LULC in the South Asia regions. LULC annual map covering the entire period is the primary dataset for climatological research. Although the LULC annual global map was produced from the Moderate Resolution Imaging Spectroradiometer (MODIS) dataset in 2001, this limited the perspective of the climatological analysis. This study used AVHRR GIMMS NDVI3g data from 2001 to 2015 to randomly forests classify and produced a time series of the annual LULC map of South Asia. The MODIS land cover products (MCD12Q1) are used as data from reference for trained classifiers. The results were verified using the annual map of the LULC time series, and the space-time dynamics of the LULC map were shown in the last 15 years, from 2001 to 2015. The overall precision of our 15-year land cover map simplifies 16 classes, which is 1.23% and 86.70% significantly maximum as compared to the precision of the MODIS data map. Findings of the past 15 years show the changing detection that forest land, savanna, farmland, urban and established land, arid land, and cultivated land have increased; by contrast, woody prairie, open shrublands, permanent ice and snow, mixed forests, grasslands, evergreen broadleaf forests, permanent wetlands, and water bodies have been significantly reduced over South Asia regions.
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Tecnologia de Sensoriamento Remoto , Imagens de Satélites , Humanos , Imagens de Satélites/métodos , Ásia Meridional , Florestas , Clima , Monitoramento Ambiental/métodos , Conservação dos Recursos Naturais/métodosRESUMO
Objective:To evaluate the effect of intrathecal exosomes derived from human amniotic fluid (hAF exo) on neuropathic pain induced by spared nerve injury (SNI) in mice.Methods:Eighteen clean-grade healthy male Kunming mice, aged 7-8 weeks, weighing 30-35 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SNI group, and SNI+ hAF exo group. Spared nerve injury was produced by exposing the sciatic nerve and its branches and ligation and transection of tibial nerve and common fibular nerve in anesthetized mice. Another three mice were selected to develop the model of neuropathic pain after anesthesia. PKH-26 labeled hAF exo 7 μl was intrathecally injected on days 1, 2 and 3 after developing the model. The mice were sacrificed at 10 h after the end of administration, and the uptake of hAF exo by the dorsal horn of the injured lumbar enlargement of the spinal cord was observed with the fluorescence microscope. On 1, 2 and 3 days after developing the model, 1 μg/μl hAF exo 7 μl was intrathecally injected in SNI+ hAF exo group, and PBS 7 μl was intrathecally injected in Sham group and SNI group. The mechanical paw withdrawal threshold (MPWT) was measured at 1 day before and 1, 3, 5 and 7 days after operation. And then the mice were sacrificed after measurement of the pain threshold at 7 days after developing the model, and the ipsilateral lumbar enlargement of the spinal cord was taken for determination of the expression of CD11b, interleukin-1beta (IL-1β) and IL-10 by Western blot. Results:The dorsal horn of the lumbar enlargement of the spinal cord on the injured side could absorb hAF exo with the fluorescence microscope. Compared with Sham group, the MPWT was significantly decreased at 3-7 days after developing the model, the expression of CD11b and IL-1β was up-regulated ( P<0.05), and no significant change was found in the expression of IL-10 in SNI group ( P>0.05). Compared with SNI group, the MPWT was significantly increased at 3-7 days after developing the model, the expression of CD11b and IL-1β was down-regulated, and the expression of IL-10 was up-regulated in SNI+ hAF exo group ( P<0.05). Conclusions:Intrathecal exosomes derived from human amniotic fluid can alleviate neuropathic pain in mice, and the mechanism may be related to mediation of the polarization of microglia from M1 type to M2 type and attenuation of neuroinflammation.
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AIM: To optimize the technique of intravenous injection of Evans blue and retinal preparations in mice, improving the accuracy and repeatability of staining experiment of retinal preparations.METHODS: C57BL/6 male mice were intravenous injected with 10g/L(1%)Evans Blue 0.3mL and circulated in vivo for 10 or 20min, and the eyes were removed after sacrificed and fixed in 4% paraformaldehyde for 20, 40 or 60min. When failure of intravenous injection, the experiment was remediated by intraperitoneal injection of 1% Evans Blue 0.3mL, circulated in vivo for 3h and fixed for 60min to observe morphology, distribution and leakage of the retinal vessels. Besides, we compared the morphology, distribution and leakage of the retinal vessels after intravenous injection with those after intraperitoneal injection to determine the optimal conditions for in vivo circulation time and retinal preparations.RESULTS: After intravenous injection, compared to the retinal vascular condition under 20min in vivo circulation time of Evans blue and 20 or 40min of fixation, with 10min of in vivo Evans blue circulation and 60min of fixation, the morphology of retinal vascular was more intact with less retinal vascular leakage, and the vascular branches are clear. When intravenous injection failed, remediated results from intraperitoneal injection showed that the morphology and distribution of retinal vessels were intact. There was no significant difference in morphology, distribution and leakage of the retinal vessels after 3h of intraperitoneal Evans blue circulation compared to 10min intravenous Evans blue circulation.CONCLUSION: This experiment optimizes the protocol, improves the accuracy and reproducibility of retinal preparations, and provides a reference for the study of related retinal vascular diseases.
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BACKGROUND: After binding to their corresponding receptors, cytokines mediate a variety of biological activities. However, the activity of cytokines in dental pulp has not been studied at the single cell level. METHODS: The cytokines activity of dental pulp was analyzed through CytoSig with the single cell sequencing data of dental pulp. RESULTS: In total, 43 cytokine signalling pathways were analyzed with CytoSig. The activity of TRAIL, NO, IL3, CXCL12 and IL1A was high in the majority of cells in dental pulp. NO, TRAIL, CXCL12, BMP4 and BMP6 had higher activity in dental pulp stem cells, whereas CXCL12, BMP4, BMP6, BMP2 and IFN1 were the cytokines with high activity in pulp cells. CONCLUSIONS: Our findings show the landscape of cytokine activity in dental pulp.
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Citocinas , Polpa Dentária , Células Cultivadas , Citocinas/metabolismo , Receptores de Citocinas , Transdução de SinaisRESUMO
Aim To explore the effeets of Salvianolie aeirl A (SAA) on platelet recruitment, activation and neutrophils in heart of myocardial infarction ( Ml ) mice.Methods C57BL/6 mice were randomly divid¬ed into: Sham operation group.Ml model group, SAA (5, 10 mg • kg 1 ) group, tirofiban (Tirofiban, 0.87 mg • kg ' ) group, using tail vein injection for 3 d.Echocardiography and HE staining were used to detect mouse heart function and infarct area; 1HC, FCS, ELISA, Western blot and other methods were used to explore the inhibitory effect of SAA on platelet and neutrophil activation.Results Compared with Ml group, SAA could improve the cardiac function and cardiac physiology changes of Ml mice, reduce the ex¬pression of CD42c in myocardial tissue and CD62p in peripheral blood without affecting tail bleeding time, reduce ADP-induced platelet activation and increase p- VASP/VASP ratio, reduce the ratio of p-PI3K/PI3K and p-AKT/AKT, reduce the expression of CD45, Ly6G, CXCL1 and CXCL2 in myocardial tissue, re¬duce the expression of complement component C3aR in myocardial tissue, and reduce C3a-induced NE and MPO, MMP9, LF level.Conclusions SAA has an anti-platelet activation effect by inhibiting the PI3K/ AKT and VASP pathways and an anti-neutrophil acti¬vation effect by inhibiting the expression of C3aR and C3a.
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Objective:To establish the grade evaluation method for Codonopsis Radix slices based relative quality constants, in order to provide scientific theoretical basis for grading of Codonopsis Radix slices. Method:Through literature and market research,the main production areas of Codonopsis Radix slices were determined,and 67 batches of Ludangshen slices(52 batches) and Baitiaodang slices (15 batches) were collected. The appearance traits (average quality and average thickness of Codonopsis Radix slices) were observed and measured. According to Chinese Pharmacopoeia (2015 edition), the extract and the content of Codonopsis pilosula polysaccharide was determined by phenol-sulphoacid method. Then the relative quality constant was calculated,and the results of grade evaluation were evaluated through systematic cluster analysis and correlation analysis. Result:Relative quality constants of 67 batches of Codonopsis Radix slices were between 0.32-2.97. If these samples were divided into three grades:the first-grade relative quality constants were greater than or equal to 2.08,the second grade was greater than or equal to 0.89 but less than 2.08,while the third grade was less than 0.89. The results of systematic cluster analysis showed that 67 batches of Codonopsis Radix slices were clustered into 3 categories,and the results were basically consistent with the classification. The correlation analysis showed a positive correlation between the content of the extracts and the polysaccharide content (P<0.05). Conclusion:This method links the extrinsic characteristics to the intrinsic quality,and objectively grade Codonopsis Radix slices, so as to provide a basis for its grade standards.
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Objective:To explore the effect of chemical compound of aconitum alkaloid on the lipopolysaccharide (LPS)-induced inflammatory response of RAW264.7 macrophages and investigate its mechanism. Method:The chemical compounds of Aconitum Kusnezoffii Reichb were collected from TCMSP database with consideration of oral bioavailability (OB)≥30% and drug-likeness (DL)≥0.18. The potential targets of each chemical component were predicted with use of Pubchem database and Swiss Target Prediction database. Rheumatoid arthritis (RA) targets were collected from GeneCards database and selected by intersection screening. Gene ontology (GO) classification enrichment and Pathway enrichment analysis were carried out with use of DAVID database. Cytoscape was used to construct "Chemical Compound-Potential Targets-Pathway-Disease" network. Protein-protein interaction (PPI) network was constructed by using STRING database and Cytoscape software. RAW264.7 macrophages were stimulated by LPS to establish macrophage inflammation model <italic>in vitro</italic>. Western blot was used to detect the effects of chemical compounds on the expression of tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>) and cyclooxygenase-2 (COX-2) in RAW264.7 cells induced by LPS, as well as on the expression of JAK kinase and nuclear transcription factor- kappa B (NF-<italic>κ</italic>B) signal pathway. Result:A total of 27 chemical compounds were obtained by searching TCMSP database and consulting literature (OB≥30%, DL≥0.18). 12 chemical compounds were obtained after screening. 177 potential targets were obtained after database prediction and screening, and 97 targets were obtained as potential targets for the treatment of RA after intersection between 177 potential targets and 4 329 RA targets. A total of 32 biological processes (BP), 5 cellular components (CC), and 12 molecular functions (MF) were enriched by DAVID database. The construction of network topology map showed that different chemical compounds can act on the same target and the same chemical compound can also act on different targets in the treatment of RA. Aconitum alkaloid can be connected with the same pathway through different targets or with different pathways through the same target, indicating that different targets may have synergistic effect, which fully reflected the complex multi-compound, multi-targets and multi-pathways mechanism. Different concentrations of LPS in stimulation (0-200 μg·L<sup>-1</sup>) can significantly up-regulate the expression of COX-2 protein in RAW264.7 macrophages (<italic>P</italic><0.05), indicating that the inflammatory model was successful. Compared with the normal group, the expression of TNF-<italic>α</italic> and COX-2 protein in the inflammatory model of RAW264.7 cells increased significantly(<italic>P</italic><0.05), while the expression of TNF-<italic>α</italic> and COX-2 protein in bulleyaconitine A(BLA), songorine, yunaconitine and karacoline groups decreased in varying degrees compared with the model group (<italic>P</italic><0.05). Compared with the normal group, the expression of IRAK4, NF-<italic>κ</italic>B, JAK1 and STAT3 in the inflammatory model of RAW264.7 cells were significantly increased (<italic>P</italic><0.05), while such levels in BulleyaconitineA, songorine, yunaconitine and Karacoline groups were significantly lower than those in the model group(<italic>P</italic><0.05). Conclusion:Based on systematic pharmacology and <italic>in vitro</italic> experiments, the related targets and signal pathways were analyzed to provide new insights into the pathogenesis of RA, reveal the molecular mechanism of aconitum alkaloid in the treatment of RA, and provide new ideas for the application of Mongolian medicine in modern medicine.
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Laryngeal and hypopharyngeal carcinomas are common malignant tumors of the head and neck, and the incidence of both is increasing. Laryngopharyngeal reflux refers to the retrograde flow of gastric contents into the larynx, oropharynx, and/or nasopharynx. It remains controversial whether laryngopharyngeal reflux is a risk factor for laryngeal and hypopharyngeal cancers. The refluxing substances mainly include hydrochloric acid, pepsin, and occasionally bile acids and bile salts, as well as bacteria that colonize the gastrointestinal tract. Loss of epithelium in the mucous membrane of the larynx and hypopharynx is thought to be caused by pepsin. Here, we review the relationships between laryngopharyngeal reflux and both laryngeal and hypopharyngeal carcinomas, as well as the significance of pepsin, methods of clinical detection, and the mechanism of carcinogenesis.
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Objective: To observe the efficacy of long-retaining scalp acupuncture plus interactive training in improving upper- extremity dysfunction in cerebral stroke patients. Methods: Ninety-five patients with upper-extremity dysfunction after cerebral stroke were randomized into two groups, with 48 cases in the treatment group and 47 cases in the control group. Conventional internal medicine treatment was offered to both groups. In both groups, Anterior Oblique Line of Vertex-temporal (MS 6, the middle 2/5) and Posterior Oblique Line of Vertex-temporal (MS 7, the middle 2/5) were selected from the same side of the brain lesion (the side apposing to the hemiplegic limb) for scalp acupuncture treatment. In the treatment group, the scalp acupuncture needles were retained for 7 h, in combination with interactive training, while the needles were also retained for 7 h in the control group but without interactive training. Prior to treatment and at 2-week and 4-week treatment, the two groups were scored using the functional test for the hemiplegic upper extremity-Hong Kong (FTHUE-HK) and simplified Fugl-Meyer assessment-upper extremity (FMA-UE). Results: The total effective rate was 97.9% in the treatment group, higher than 74.5% in the control group (P<0.01). The FTHUE-HK score was higher at 2-week and 4-week treatment than before treatment in both groups, presenting statistically significant intra-group differences (all P<0.001); the FTHUE-HK score was higher at 4-week treatment than at 2-week treatment in both groups, presenting statistically significant intra-group differences (both P<0.001). At 2-week and 4-week treatment, the FTHUE-HK score was higher in the treatment group than in the control group, showing significant between-group differences (both P<0.05). During the whole treatment process, the treatment group had higher FTHUE-HK scores compared with the control group, but there was no statistical significance comparing the change of the score between the two groups at 2-week treatment (P>0.05), while the between-group difference in the change of the score was statistically significant at 4-week treatment (P<0.05). The FMA-UE score was higher at 2-week and 4-weeks treatment than before treatment in both groups, presenting statistically significant intra-group differences (all P<0.001); the FMA-UE score was higher at 4-week treatment than at 2-week treatment in both groups, presenting statistically significant intra-group differences (both P<0.001). At 2-week and 4-week treatment, the FMA-UE was higher in the treatment group than in the control group, and the between-group differences were statistically significant (both P<0.01). The FMA-UE score rose gradually with the increase of treatment session, and there was statistical significance comparing the change of the score between the two groups at 2-week and 4-week treatment, respectively (both P<0.05). Conclusion: Long-retaining scalp acupuncture plus interactive training results in more significant efficacy than long-retaining scalp acupuncture alone in improving the upper-limb dysfunction after cerebral stroke and the advantage becomes more notable after 2-week consecutive treatment.
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OBJECTIVE:To provide reference for the development and application of pharmacy popular-science video courseware. METHODS :Combined with the problems existing in the medication of patients with chronic diseases at the present stage and the key points of medication management ,the theme ,content and form of this popular-science were determined ;the video shooting and production were completed ,and publicity and promotion were carried out. Questionnaire survey was conducted , and the reception of pharmacy outpatient service in our hospital was counted ;the broadcasting effects of popular-science video were analyzed. RESULTS :The theme of popular-science video courseware was determined to be self-medication management of patients with chronic diseases at home assisted by pharmacists. Combined with the “five moments ”of medication safety proposed by WHO , the content included six units as knowing pharmacists ,understanding drugs ,taking drugs ,adding drugs ,checking drugs ,and discontinuing drugs. PPT video was used to explain the contents of each unit ,with an average duration of about 25 min. After the first unit was launched ,a total of 39 327 hits were received within two months. A total of 100 questionnaires were sent out ,97 questionnaires were collected (recovery rate of 97.0%). Among them ,80(82.5%)thought it helpful to watch the video. Within two months after the broadcast of unit 1 video,the reception volume of pharmacy outpatient department of our hospital (1 160 person times )increased by 104.2% compared with the two months in the same period last year (568 person times ),and increased by 18.7% compared with the two months before the broadcast (977 person times );99 patients came to the pharmacy outpatient department to consult because of watching the video ,and 55.6% of the registered patients consulted the demonstration of video courseware and repeatedly mentioned related problems. CONCLUSIONS :It is a beneficial exploration for pharmacists to develop popular-science video courseware with the theme of safe and rational drug use. It is the direction for future work to increase the scope of disease types ,target different groups of people or focus on different types of drugs and promot them in various forms.
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Objective:To evaluate the role of secreted phosphoprotein 1 (SPP1) in endogenous protective mechanism underlying neuropathic pain (NP) in mice with spinal cord injury and the relationship with the vascular endothelial growth factor (VEGF)/kinase B (Akt) signaling pathway.Methods:Seventy-two clean-grade healthy female Kunming mice, aged 7-8 weeks, weighing 30-35 g, were divided into 4 groups ( n=18 each) using a random number table method: sham group (Sham group), NP caused by spinal cord injury group (NP group), NP caused by spinal cord injury+ SPP1-siRNA group (NS-siRNA group), and NP caused by spinal cord injury+ adeno-associated virus vector group (NP-EV group). A model of NP was established by a semi-transecting of the spinal cord.AAV-SPP1-siRNA-GFP adenovirus and AAV-vector-GFP adenovirus 7 μl were intrathecally injected in NS-siRNA group and NP-EV group, respectively, and 5 days later the model was established.At 1, 2 and 3 weeks after operation, 6 mice in each group were randomly selected to measure paw withdrawal threshold to mechanical stimulation (PWMT) and tail flick latency (TFL) to thermal stimuli.And then the mice were sacrificed and the ipsilateral injured spinal cord tissues were taken for determination of the expression of SPP1 mRNA (by real-time polymerase chain reaction) and expression of SPP1, VEGF, Akt and phosphorylated Akt (p-Akt) (by Western blot). Results:Compared with group Sham, PWMT was significantly decreased, TFL was shortened, and the expression of SPP1 mRNA, SPP1, VEGF and p-Akt protein was up-regulated at 1, 2 and 3 weeks after operation in NP, NS-siRNA and NP-EV groups( P<0.05). Compared with group NP, PWMT was significantly decreased, TFL was shortened, and the expression of SPP1 mRNA, SPP1, VEGF and p-Akt protein was down-regulated at 1, 2 and 3 weeks after operation in group NS-siRNA( P<0.05). Compared with group NS-siRNA, PWMT was significantly increased, TFL was prolonged, and the expression of SPP1 mRNA, SPP1, VEGF and p-Akt protein was up-regulated at 1, 2 and 3 weeks after operation in group NS-siRNA( P<0.05). Conclusion:SPP1 is involved in the endogenous protective mechanism underlying NP in mice with spinal cord injury, which may be related to the activation of the VEGF/AKT signaling pathway.
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OBJECTIVE: To explore the mediating role of doctor-patient relationship between occupational stress and job burnout of medical staffs involved in the prevention and treatment of patients with acquired immune deficiency syndrome(AIDS) and the regulating role of personality traits. METHODS: A total of 346 medical staffs who are involved in AIDS prevention and treatment from 29 antiviral treatment sites in Yunnan Province were selected as the study subjects using convenience sampling method. The Questionnaire of Doctor-Patient Interaction, Subscale of Feeling Stress, Questionnaire of Chinese Job Burnout, and China′s Big Five Personality Questionnaire(short version) were used to investigate these subjects. The mediating-regulating model was tested with the Process program. RESULTS: The total scores of doctor-patient relationship, occupational stress, personality traits and job burnout were(43.6±9.2),(153.1±29.5),(156.2±17.9) and(67.7±16.8), respectively. The job burnout was associated with doctor-patient relationship and occupational stress(correlation coefficients were-0.31 and 0.24, respectively, all P<0.05). Occupational stress had a direct effect on job burnout(P<0.01). The doctor-patient relationship had a mediating effect between occupational stress and job burnout(P<0.05), which accounted for 13.1% of the total effect. It was regulated by open personality traits(P<0.01). CONCLUSION: The doctor-patient relationship has a mediating effect between the occupational stress and job burnout of the medical staffs engaged in AIDS prevention and treatment, and the open personality traits plays a moderating role.
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OBJECTIVE@#LAPTM4B-35 protein is one of the isoforms that are encoded by a cancer driver gene, LAPTM4B. This gene was primarily found and identified in our lab of Peking University School of Basic Medical Sciences. The LAPTM4B-35 protein and its encoded mRNA are significantly over-expressed in a variety of cancers, such as hepatocellular carcinoma (HCC), lung cancers (including non small-cell lung cancer and small-cell lung cancer), stomach cancer, colorectal carcinoma, pancreatic cancer, gallbladder cancer, cholangiocarcinoma, breast cancer, prostate cancer, ovarian cancer, cervical cancer, endometrial cancer, and so on. It has firmly demonstrated through lab experiments either in vivo or in vitro, as well as clinical studies that the over-expression of LAPTM4B-35 can promote cancer growth, metastasis, and multidrug resistance. Specially, the expressive level of LAPTM4B-35 is associa-ted with recurrence of HCC. The aim of this study is to identify the release of LAPTM4B-35 protein from hepatocellular carcinoma into blood of HCC patients and into the medium of cultured HCC cells, and to identify its possible form of LAPTM4B-35 protein existed in blood and cell culture medium, as well as to explore the possibility of LAPTM4B-35 protein as a novel HCC biomarker for diagnosis of HCC and prognosis of HCC patients.@*METHODS@#Immunobloting (Western blot) and enzyme-linked immunosorbent assay (ELISA) were used for identification of LAPTM4B-35 protein in the blood of HCC patients and normal individuals. Ultrafiltration and ultracentrifugation were used to isolate and purify exosomes from the culture medium of HCC cells.@*RESULTS@#LAPTM4B-35 protein existed in the blood from HCC patients and normal donors that were demonstrated through Western blot and ELISA. LAPTM4B-35 was also released into the culture medium of HCC cells in the form of exosomes. Preliminary experiments showed that the average and the median of LAPTM4B-35 protein level in the blood of HCC patients (n=43) were both significantly higher than that in the blood of normal donors (n=33) through sandwich ELISA.@*CONCLUSION@#It is promising that the LAPTM4B-35 protein which is released from HCC cells in the form of exosomes into their extraenvironment may be exploited as a novel cancer biomarker for HCC serological diagnosis.
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Humanos , Masculino , Biomarcadores Tumorais , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Proteínas de Membrana/genética , Proteínas Oncogênicas , PrognósticoRESUMO
Aim To explore the effect of aucubin aucubin (AU), one of the effective ingredients of eucommia, plantain, rehmannia and other herbs, on cardiomyocyte apoptosis and cardiac function after acute myocardial infarction (MI) and the possible mechanisms. Methods In this study, the mouse models of MI were established by ligation of the anterior descending branch of the left coronary artery. Left ventricular function and the infarct size were detected using echocardiography and Masson staining. A Tumor necrosis factor-a (TNF-ot)/cycloheximide (C H X) model of cardiomyocyte injury was established, and the effects AU on myocardial injury were examined using IncuCyte live cell imaging, Western blot and TUNEL staining. Results AU administration dramatically improved cardiac function recovery and decreased infarct size after MI. AU inhibited the apoptosis of cardiomyocytes, reduced the expressions of caspase-3, and significantly increased the ratio of Bcl-2/Bax induced by TNF-ot/ CHX. Meanwhile, the estrogen receptor ß (ERß) protein level was elevated by AU, and the antiapoptotic effect of AU was blocked by ERß inhibitor. Conclusions AU can alleviate MI injury and improve cardiac function via inhibiting the apoptosis of cardiomyocytes, and its mechanism is the activation of ERß pathway.
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Laryngeal and hypopharyngeal carcinomas are common malignant tumors of the head and neck, and the incidence of both is increasing. Laryngopharyngeal reflux refers to the retrograde flow of gastric contents into the larynx, oropharynx, and/or nasopharynx. It remains controversial whether laryngopharyngeal reflux is a risk factor for laryngeal and hypopharyngeal cancers. The refluxing substances mainly include hydrochloric acid, pepsin, and occasionally bile acids and bile salts, as well as bacteria that colonize the gastrointestinal tract. Loss of epithelium in the mucous membrane of the larynx and hypopharynx is thought to be caused by pepsin. Here, we review the relationships between laryngopharyngeal reflux and both laryngeal and hypopharyngeal carcinomas, as well as the significance of pepsin, methods of clinical detection, and the mechanism of carcinogenesis.
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In South Asia, key differences in annual land use and land cover (LULC) take place due to climate change, global warming, human activity, biodiversity, and hydrology. So, it is very important to get accurate land cover information for this region. An annual LULC map that covers a comprehensive period is a major dataset for climatologically study. While yearly worldwide maps of LULC are produced from Moderate Resolution Imaging Spectroradiometer (MODIS) dataset, in 2001, the first LULC map of MODIS is generated which restrictions the perspective climatologically analysis. This research work generated a time series of yearly LULC maps of South Asia from 2001 to 2015 by using random forest classification from AVHRR GIMMS NDVI3g data. The MODIS land cover product such as (MCD12Q1) was used as a reference data for the trained classifier. The result was validated by using time series of annual LULC maps, and the spatiotemporal dynamic of LULC maps was illustrated in the last 15 years from 2001 to 2015. The simplified sixteen class versions of our 15-year overall accuracy of a land cover map are 86.70%, and 1.23% higher than that of MODIS maps. The change detection indicated that, for the last 15 years, the class of closed shrublands, savannas, croplands, urban and built-up land, barren, and cropland per natural vegetation mosaics increase notably during the 2001 to 2015, and in contrast, the class of woody savannas, evergreen needleleaf forests, open shrublands, grasslands, mixed forests, permanent wetlands, permanent snow and ice, evergreen broadleaf forests, and water bodies decrease notably during 2001 to 2015. These yearly land cover maps will be an essential dataset for the upcoming climate study, where time series of LULC maps accessibility is restricted.
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Hidrologia , Imagens de Satélites , Ásia , Biodiversidade , Mudança Climática , Conservação dos Recursos NaturaisRESUMO
In this study, the effect of benzo[α]pyrene (BaP) on chaperone-mediated autophagy (CMA) in a simulated hypoxia environment was observed and the relationship to heat shock protein 90 (HSP90) was clarified. With HSP90 inhibitor geldanamycin (GA) and HSP90α silenced, the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), HSP90, heat shock cognate protein 70 (HSC70), and lysosomal associated protein 2A (LAMP-2A) of A549 cells on hypoxic environment by BaP were tested. Alkaline comet experiment, immunofluorescence γ-H2AX focus experiment, quantitative real-time PCR (qPCR), and Western blot analyses were used to clarify the relationship between the DNA damage of different concentrations of BaP in A549 cells and the mRNA and protein expression of CMA-related factors. The results show that hypoxia can promote the expression of mRNA and protein of CMA-related factors in A549 cells. This study found that BaP has an inhibitory effect on CMA under the hypoxic environment. The inhibition or silencing of HSP90 will enhance the inhibitory effect of BaP on CMA. In a normoxic environment, BaP causes DNA damage and promotes CMA.
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<p><b>OBJECTIVE</b>To study the effects of Astragalus polysaccharide (APS), the primary effective component of the Chinese herb medicine Astragalus membranaceus (frequently used for its anti-hepatic fibrosis effects), on nanoscale mechanical properties of liver sinusoidal endothelial cells (SECs).</p><p><b>METHODS</b>Using endothelial cell medium as the control, 5 experimental groups were established utilizing different concentrations of APS, i.e. 12.5, 25, 50, 100, and 200 μg/mL. By using atomic force microscopy along with a microcantilever modified with a silicon dioxide microsphere as powerful tools, the value of Young's modulus in each group was calculated. SAS 9.1 software was applied to analyze the values of Young's modulus at the pressed depth of 300 nm. Environmental scanning electron microscopy was performed to observe the surface microtopography of the SECs.</p><p><b>RESULTS</b>The value of Young's modulus in each APS experimental group was significantly greater than that of the control group: as APS concentration increased, the value of Young's modulus presented as an increasing trend. The difference between the low-concentration (12.5 and 25 μg/mL) and high-concentration (200 μg/mL) groups was statistically significant (P<0.05), but no significant differences were observed between moderateconcentration (50 and 100 μg/mL) groups versus low- or high-concentration groups (P>0.05). Surface topography demonstrated that APS was capable of increasing the total area of fenestrae.</p><p><b>CONCLUSIONS</b>The values of Young's modulus increased along with increasing concentrations of APS, suggesting that the stiffness of SECs increases gradually as a function of APS concentration. The observed changes in SEC mechanical properties may provide a new avenue for mechanistic research of anti-hepatic fibrosis treatments in Chinese medicine.</p>
Assuntos
Animais , Ratos , Astrágalo , Química , Fenômenos Biomecânicos , Módulo de Elasticidade , Células Endoteliais , Biologia Celular , Fígado , Biologia Celular , Microscopia de Força Atômica , Microesferas , Nanotecnologia , Polissacarídeos , Farmacologia , Dióxido de Silício , Química , Propriedades de SuperfícieRESUMO
OBJECTIVE:To provide reference for promoting smoothly implementation of deprescribing. METHODS:A total of 335 elderly patients with chronic disease were randomly selected from 4 communities and 9 village clinic of a Chongqing community health service center. Questionnaire survey was conducted about general information of respondents,disease and drug use condition and attitude to deprescribing by using Australian Patients'Attitudes Towards Deprescribing questionnaire as reference. The results of questionnaire survey were analyzed statistically. The cognitive function was assessed by Hastgawa Dementia Scale. The degree of weakness was evaluated by Chinese edition of Edmonton Frail Scale. The quality of life was evaluated by Chinese edition of European Five Dimensional Health (EQ-5D) Scale. RESULTS:Totally 311 valid questionnaires were obtained,with effective recovery rate of 92.8%. Overall,311 participants were recruited,with a median age of 70 years,5 types of median disease (hypertension was most common) and 5 types of median medication (mainly calcium channel blocker and non-insulin hypoglycemic agent);54.7%(170 cases)participants took multiple drugs. The attitudes towards deprescribing were that 39.5% of respondents believed that they took too many drugs;73.9% had a desire to reduce their drugs;83.6% reported that they would be willing to reduce drugs if their doctor said it was possible. The patients taking multiple drugs preferred to use less drugs (P=0.001) and reduce current drugs (P=0.001),and were more willing to reduce drug cost by reducing drug use;they were also more worried about drug side effects than those without taking multiple drugs (P=0.005). CONCLUSIONS:The phenomenon of elderly chronic diseases patients with multiple diseases and multiple drug use are popular in community. It is necessary to simpilfy prescription. Most elderly patients would like to reduce their medications if doctors say it is possible;the patients with multiple drug use are more willing to simplify prescription than those without multiple drug use.