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1.
Sensors (Basel) ; 23(5)2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36904903

RESUMEN

The development of inertial confinement fusion (ICF) experiments necessitates the diagnostic instrument to have multiple frames with a high spatial and temporal resolution for the two-dimensional detection of the hot spot at the implosion end of the ICF. The existing sampling two-dimensional imaging technology in the world has superior performance; however, its subsequent development requires a streak tube with large lateral magnification. In this work, an electron beam separation device was designed and developed for the first time. The device can be used without changing the structure of the streak tube. It can be combined directly with the corresponding device and matched with a special control circuit. Based on the original transverse magnification, 1.77 times the secondary amplification can be achieved, which is conducive to expanding the recording range of the technology. The experimental results showed that the static spatial resolution of the streak tube after the inclusion of the device can still reach 10 lp/mm.

2.
Neurochem Res ; 45(8): 1769-1780, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32415405

RESUMEN

The mechanism of cognitive dysfunction in diabetes is still unclear. Recently, studies have shown that the cerebellum is involved in cognition. Furthermore, diabetes-induced cerebellar alterations is related to vascular changes. Therefore, we aimed to explore the roles of vascular function in diabetes-induced cerebellar damage and motor learning deficits. Type 1 diabetes was induced by a single injection of streptozotocin in Sprague-Dawley rats. Motor learning was assessed by beam walk test and beam balance test. The pathological changes of the cerebellum were assessed by Hematoxylin and eosin staining and Nissl staining. Apoptosis was evaluated by anti-caspase-3 immunostaining. Protein expression was evaluated by western blotting and double immunofluorescence. Our results have shown that motor learning was impaired in diabetic rats, coupled with damaged Purkinje cells and decreased capillary density in the cerebellum. In addition, the protein expression of neuronal NOS, inducible NOS, endothelial NOS, total nitric oxide, vascular endothelial growth factor and its cognate receptor Flk-1 was decreased in the cerebellum. Gastrodin treatment ameliorated neuronal damage and restored protein expression of relevant factors. Arising from the above, it is suggested that vascular dysfunction and NO signaling deficits in the cerebellum may be the underlying mechanism of early manifestations of cognitive impairment in diabetes, which could be ameliorated by gastrodin intervention.


Asunto(s)
Conducta Animal/efectos de los fármacos , Alcoholes Bencílicos/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Glucósidos/uso terapéutico , Locomoción/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Corteza Cerebelosa/efectos de los fármacos , Corteza Cerebelosa/enzimología , Corteza Cerebelosa/patología , Disfunción Cognitiva/epidemiología , Diabetes Mellitus Experimental/complicaciones , Endotelio Vascular/efectos de los fármacos , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Células de Purkinje/efectos de los fármacos , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo
3.
Nano Lett ; 19(8): 4897-4903, 2019 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-30973231

RESUMEN

Creation of functional patterns in two-dimensional (2D) materials provides opportunities to extend their potential for applications. Transition-metal dichalcogenides (TMDCs) are suitable 2D materials for pattern generation because of properties including alterable polymorphic phases, easy chalcogen-vacancy formation, metal-atom insertion, and alloying. Such patterning can be used for selective functionalization. Here we report the spontaneous formation of long-range, well-ordered 1D patterns in monolayer vanadium diselenide (VSe2) by a single annealing stage during growth. Atomic-resolution images in real space combined with density-functional-theory (DFT) calculations reveal the 1D features of patterned VSe2. Further experimental characterization of the intermediate states in the growth process confirm the spontaneous formation of the 1D pattern by annealing-induced Se-deficient linear defects. The 1D pattern can be reversibly transformed to homogenous VSe2 monolayer by reintroducing Se atoms. Moreover, additional experiments demonstrate that a dispersive deposition of Pt atoms along the 1D structures of patterned VSe2 is achieved, while DFT calculations find that their catalytic activity for hydrogen evolution reaction (HER) is as good as that of Pt surfaces. The formation of long-range, well-ordered 1D patterns not only demonstrates an effective way of dimension modulation in 2D materials but also enriches the potential of intrinsically patterned 2D materials for promising catalytic activities.

4.
Clin Invest Med ; 40(2): E81-E94, 2017 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-28447581

RESUMEN

PURPOSE: Cisplatin-based neoadjuvant chemotherapy (NAC) has been shown to improve survival in patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy as compared with patients who underwent surgery alone. It has also been suggested as current standard of care in surgically-fit patients with MIBC. This meta-analysis assessed the effect of cisplatin-based NAC on survival in patients with bladder cancer. SOURCE: PubMed, CENTRAL, and Embase were searched until November 22, 2016. Two-arm randomized controlled trials that compared cisplatin-based neoadjuvant chemotherapy plus local treatment versus the same local treatment without neoadjuvant chemotherapy were selected. Patients with histologically-confirmed bladder cancer (adenocarcinoma, transitional, or squamous-cell carcinoma) were included. The primary outcome was overall survival (OS). PRINCIPAL FINDINGS: Of the 292 articles initially identified, 14 were included in the final analysis. Patients in the NAC group had similar OS as the local treatment (i.e., radiation therapy or cystectomy) group (pooled hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.84 to 1.00, P=0.056). No difference in progress-free survival between two groups was observed (P=0.725). Subgroup analysis showed that OS was similar in patients treated with NAC plus radiotherapy or cystectomy compared with patients who received local treatment alone. CONCLUSIONS: Platinum-based NAC was associated with similar survival benefit as patients undergoing cystectomy and/or radiotherapy. No conclusion can be drawn about the optimal platinum-based combination to be used in the neoadjuvant setting.


Asunto(s)
Cisplatino/uso terapéutico , Terapia Neoadyuvante/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Femenino , Humanos , Masculino , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología
5.
Postepy Hig Med Dosw (Online) ; 71(0): 352-358, 2017 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-28513459

RESUMEN

The antimicrobial function of neutrophils, which is dependent on opsonin receptors, deteriorates in severe acute pancreatitis (SAP). Granulocyte colony-stimulating factor (G-CSF) putatively enhanced levels of the opsonin receptors CD11b and CD32/16 in healthy human subjects, and provided protection against infection in animal models of SAP. A statistically convincing study of the effect of G-CSF on CD32/16 expression in an SAP model is lacking. We used a mouse model of SAP to investigate the association between G-CSF administration and CD32/16 levels on neutrophils and bacterial translocation. G-CSF or saline was subcutaneously injected into SAP-induced mice. The pancreases were histologically examined, and leukocytes were stained to count neutrophils. The expression of CD11b and CD32/16 on neutrophils was measured by flow cytometry, and bacterial translocation was observed by bacterial culture. The numbers of CD11b and CD32/16-positive neutrophils were significantly elevated in the SAP mice treated with G-CSF, and the mean fluorescence intensities of these receptors on neutrophils were significantly elevated. Bacterial translocations to cavity organs were suppressed from 17% to 6% by G-CSF treatment. Our results indicated that the number of neutrophils significantly increased with increasing expression of CD11b and CD32/16 and their mean fluorescence intensities (MFIs). This inhibited bacterial translocation to other organs. These results are in accord with other studies in SAP dogs and SAP mice. Our findings suggest that G-CSF was effective in protecting against bacterial infection in SAP mice.


Asunto(s)
Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Activación Neutrófila/efectos de los fármacos , Pancreatitis/fisiopatología , Receptores Inmunológicos/efectos de los fármacos , Enfermedad Aguda , Animales , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/inmunología , Femenino , Regulación de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos/farmacología , Ratones , Pancreatitis/tratamiento farmacológico , Pancreatitis/inmunología , Receptores Inmunológicos/genética
6.
Immunotherapy ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38532729

RESUMEN

Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with limited treatment options, especially for extensive-stage (ES) patients. We present a case of a 70-year-old male with ES-SCLC and asymptomatic brain metastasis who opted for immune monotherapy with serplulimab (an anti-PD-1 antibody). After four cycles, the patient achieved a confirmed partial response and a progression-free survival of over 1 year. Moreover, we observed a consistent decline in tumor biomarkers, and brain MRI indicated reduced metastatic activity. Remarkably, the patient tolerated the treatment well, with only mild diarrhea. This case highlights serplulimab's potential as a first-line treatment in select ES-SCLC patients, emphasizing the importance of further research on immunotherapy predictive biomarkers.


Small-cell lung cancer (SCLC) is a severe type of lung cancer that often does not have many treatment options, especially in its advanced stages. This article discusses the experience of a 70-year-old man with advanced SCLC who also had cancer spread to his brain but did not show symptoms. He chose to try a new kind of cancer treatment called serplulimab, which works by helping the immune system fight the cancer. After receiving this treatment four-times, his cancer showed significant improvement, and he did not experience further cancer growth for more than 1 year. Tests also revealed that his cancer markers decreased, and the cancer in his brain became less active. Notably, he tolerated this agent with only mild diarrhea occurring. This case is important because it suggests that serplulimab could be an effective first treatment for some patients with advanced SCLC, and it highlights the need for more research to find ways to predict who will benefit from this type of therapy.

7.
Minerva Anestesiol ; 88(10): 789-796, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35546734

RESUMEN

BACKGROUND: The aim of this study was to observe changes in the laryngeal vestibule under head extension or in neutral position with or without the chin lifted after anesthesia induction. METHODS: After anesthesia induction, a flexible bronchoscope was used to observe the status of the laryngeal vestibule under four positions. Then, the degree of laryngeal vestibule closure was graded. The grading scores and the incidence of severe closure under these four positions were compared. The factors that may be related to the severe closure and potential contributions of head extension and chin lifting were also analyzed. When laryngeal mask was applied, the change in the laryngeal vestibule state was observed through the laryngeal mask after placement. RESULTS: The closure scores of the laryngeal vestibule were significantly different among these four positions (P<0.001). The incidence of severe closure was highest in the neutral head position without the chin lifted. Regression analysis showed that age and snoring were associated with severe closure of the laryngeal vestibule. Both head extension and chin lifting could decrease the risk of severe closure of the laryngeal vestibule, and head extension was more important than chin lift. After laryngeal mask placement, the severely closed laryngeal vestibule can be further opened up to grades 1-2. CONCLUSIONS: The neutral position of the head after anesthesia induction may cause complete closure of the laryngeal vestibule. The best way to keep the laryngeal vestibule open is head extension with the chin lifted, while most the laryngeal vestibules will be severely closed in the neutral position without the chin lifted.


Asunto(s)
Máscaras Laríngeas , Laringe , Anestesia General , Humanos , Máscaras Laríngeas/efectos adversos , Postura
8.
Brain Sci ; 12(8)2022 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-35892429

RESUMEN

BACKGROUND: Emergence delirium (ED) occurs immediately after emergence from general anesthesia, which may have adverse consequences. This cross-sectional survey assessed Chinese physicians' and nurses' knowledge of, attitudes towards, and practice regarding ED in adults. METHODS: Electronic questionnaires were sent to 93 major academic hospitals across mainland China and both attending anesthesiologists and anesthesia nurses were recommended to complete them. RESULTS: A total of 243 anesthesiologists and 213 anesthesia nurses participated in the survey. Most of the participants considered it a very important issue; however, less than one-third of them routinely assessed ED. In terms of screening tools, anesthesiologists preferred the Confusion Assessment Method, while anesthesia nurses reported using multiple screening tools. Divergence also appeared with regard to the necessity of monitoring the depth of anesthesia. Anesthesiologists considered it only necessary in high-risk patients, while the nurses considered that it should be carried out routinely. No unified treatment strategy nor medication was reported for ED treatment during the recovery period. CONCLUSIONS: This study illustrated that there are high awareness levels among both Chinese anesthesiologists and anesthesia nurses regarding the importance of ED. However, a specific practice in terms of routine delirium assessment, anesthesia depth monitoring, and a standardized treatment algorithm needs to be implemented to improve ED management.

9.
Hum Cell ; 34(1): 165-176, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32951177

RESUMEN

Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. Tumor suppressor long noncoding RNA on chromosome 8p12 (TSLNC8) is a newly identified long noncoding RNA (lncRNA) and play an important role in human cancers. However, the function and molecular mechanism of TSLNC8 in PC progression remain to be elucidated. Our results showed a significant increase of TSLNC8 expression in PC tissues and cell lines. Upregulation of TSLNC8 expression in PC tissues was closely correlated with TNM stage, distant and lymph node metastasis, and poor prognosis of PC patients. Functional experiments demonstrated that TSLNC8 promoted PC cells proliferation and invasion in vitro, and enhanced PC growth and metastasis in vivo. Mechanistically, TSLNC8 associated with HuR, promoted the binding of HuR with CTNNB1 mRNA and increased the stability of CTNNB1 mRNA, thus activating WNT/ß-catenin signaling pathway. Taken together, our present study revealed that oncogenic lncRNA TSLNC8 positively regulate PC growth and metastasis via HuR-mediated mRNA stability of CTNNB1, extending the understanding of PC pathogenesis regulated by lncRNAs.


Asunto(s)
Proteína 1 Similar a ELAV/genética , Proteína 1 Similar a ELAV/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Expresión Génica/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/fisiología , beta Catenina/genética , beta Catenina/metabolismo , Línea Celular Tumoral , Genes Supresores de Tumor , Humanos , Regulación hacia Arriba , Vía de Señalización Wnt/genética , Vía de Señalización Wnt/fisiología
10.
Nanoscale ; 12(32): 17005-17012, 2020 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-32780052

RESUMEN

Rhenium dichalcogenides (ReX2, X = S, Se), as a representative type of T''-phase transition metal dichalcogenides (TMDs), have a distinct anisotropic crystal structure as compared to the well-known H- and T-phases and show excellent optical, electronic and catalytic properties. While edges are known to have a profound influence on the physical and chemical properties of two-dimensional materials, they have not been systematically investigated in T''-phase TMDs. We investigated the pristine edge configurations of ReX2 atomic layers using atomic-resolution scanning transmission electron microscopy (STEM) low-dose imaging and density functional theory (DFT) calculations. The pristine edges in monolayer and bilayer ReX2 can be atomically flat with a length up to several tens of nanometers, and are preferentially oriented along either the a axis or b axis. The characteristic 4Re diamond clusters are well preserved along the edges, and ordered structures of the outermost dangling Se atoms were observed, with the Se atoms fully retained, 50% retained or all lost. The edges oriented along the a axis with 100% Se coverage show a ferromagnetic ground state, while their counterparts parallel to b present mid-gap states without appreciable spin-polarization. The anisotropic T'' structure also dictates the cracking direction in ReX2, with cracks propagating mainly along the a and b axes. The strain at the crack edges often causes re-orientation of the lattice, which would change the anisotropic behavior of ReX2. Our work provides new insights into the edge configuration in T'' TMD atomic layers, and offers new opportunities to tailor the performance of ReX2 by edge engineering.

11.
Medicine (Baltimore) ; 98(44): e17680, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31689787

RESUMEN

Hepatocellular carcinoma (HCC) is a lethal disease worldwide. In this study, we sought to explore the expression of insulin-like growth factor-1 receptor (IGF-1R) and its prognostic value in HCC.The expressions of IGF-1R mRNA and protein were estimated using quantitative real-time polymerase chain reaction and immunohistochemistry assays, respectively. The association between IGF-1R expression and clinicopathologic characteristic of patients with HCC was analyzed through Chi-squared test. Kaplan-Meier analysis and multivariate Cox analysis were performed to analyze prognostic value of IGF-1R in HCC.The IGF-1R was significantly upregulated in HCC tissues at both mRNA and protein levels compared with adjacent normal ones (P < .01). Its expression was associated with tumor node metastasis stage (P = .037) and lymph node metastasis (P = .027) of patients with HCC. Patients with HCC with high expression of IGF-1R had worse overall survival than those with low expression. IGF-1R might be a potential prognostic biomarker for HCC (hazard ratio [HR] = 1.912, 95% confidence interval [CI]: 1.023-3.572, P = .042).The IGF-1R expression level is upregulated in HCC tissues and may act as a prognostic biomarker for the disease.


Asunto(s)
Carcinoma Hepatocelular/patología , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Neoplasias Hepáticas/patología , Anciano , Biomarcadores de Tumor , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba
13.
Artículo en Zh | WPRIM | ID: wpr-1030939

RESUMEN

ObjectiveTo explore host factors interacting with influenza virus nucleoprotein (NP) and study their effects on influenza virus replication, as well as the mechanism of gardenia jasminoides iridoid glycoside (IGE) in inhibiting influenza virus. MethodA yeast two-hybrid system was utilized to screen host factors that interacted with influenza virus NP. Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD), glucosamine-6-phosphate deaminase 1 (GNPDA1), poly(rC)-binding protein 1 (PCBP1), and protein inhibitor of activated signal transducer and activator of transcription (STAT) protein 1 (PIAS1) were validated by immunoprecipitation assay. The effects of PIAS1 and HNRNPD on influenza virus replication were compared by a dual luciferase assay, and the effects of IGE on influenza virus replication were examined in the presence of transfected ribonucleoprotein (RNP) and knockdown of PIAS1. ICR mice were randomly divided into a normal group, model group, oseltamivir phosphate group, and high, medium, and low dose IGE groups, with 10 mice in each group. In addition to the normal group, each group was infected with the influenza A virus FM1 strain by nasal drip to establish a viral pneumonia model. The high, medium, and low dose IGE groups were given drugs of 50, 25, and 12.5 mg∙kg-1 by gavage, and the oseltamivir phosphate group was given the drug of 27.5 mg∙kg-1 by gavage. Equal amounts of distilled water were instilled in the normal and model groups for four consecutive days. Later, protein expression of PIAS1, NP, phosphorylated (p)-STAT3, STAT3, p-STAT1, and STAT1 were detected in the lung tissue by Western blot. ResultIn yeast two-hybrid assays, 16 potential host targets interacting with influenza virus NP were identified. Immunoprecipitation experiments revealed that HNRNPD and PIAS1 could interact with influenza virus NP. The dual luciferase reporter assays found that both PIAS1 knockdown and overexpression significantly affected IAV RNP activity (P<0.05, P<0.01), and the effect of HNRNPD on IAV RNP was not significant. Both high and low dose IGE groups reduced influenza virus replication (P<0.05) and reversed the increase in influenza virus replication caused by the knockdown of PIAS1(P<0.05, P<0.01). The expressions of PIAS1, NP, p-STAT3, p-STAT1, and STAT1 in the lung tissue of infected mice were reduced to different degrees in each IGE group (P<0.05, P<0.01). ConclusionPIAS1 interacts with influenza virus NP and is able to inhibit influenza virus replication. IGE may exert antiviral effects by inhibiting the activity of IAV RNP through the PIAS1/STAT1 pathway.

14.
Chongqing Medicine ; (36): 114-120, 2024.
Artículo en Zh | WPRIM | ID: wpr-1017449

RESUMEN

Objective To systematically retrieve,evaluate and integrate the best evidences on the early fluid resuscitation management in the patients with acute pancreatitis(AP)at home and abroad to provide ref-erence for clinical decision.Methods The related evidences on the early fluid resuscitation management in the AP patients were retrieved by computer from the databases of BMJ Best Practice,Up To Date,JBI,National Institute for Health and Care Excellence,Registered Nurses Association of Ontario,Guideline International Network,Scottish Intercollegiate Guidelines Network,International Association of Pancreatology,American Pancreatic Association,American College of Gastroenterology,Yimaitong,Cochrane Library,PubMed,Em-bass,CINAHL,The Web of Science,CNKI,Wanfang databases.The retrieval time limit was from the data-base establishment to March 20,2022.The literatures types included thematic evidence summarization,guide-lines,evidence summaries,systematic reviews and expert consensus.The researchers conducted the literature quality evaluation.The literatures meeting the standard conducted the evidence extraction.Results A total of 13 arti-cles were included,including 3 special subject evidence summary,4 guidelines,2 evidence summary,2 systematic evalu-ation and 2 expert consensus.A total of 16 pieces of best evidence were integrated,involving 4 aspects of organization management,evaluation and monitoring,fluid infusion strategy and health education.Conclusion It is recommended to use the target-oriented therapy for early fluid resuscitation management,and perform the fluid resuscitation immediate-ly after diagnosis,according to the patient's underlying disease,disease changes and monitoring indicators,implement precise early fluid resuscitation in order to reverse pancreatic microcirculation disorder,increase tissue perfusion and improve the patient's prognosis.

15.
Chongqing Medicine ; (36): 738-744, 2024.
Artículo en Zh | WPRIM | ID: wpr-1017528

RESUMEN

Objective To develop nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia,and test its reliability and validity.Methods Based on the evidence-based summary of the best evidence of medication management for patients with dysphagia,guided by the the-ory of knowledge,attitude and practice,the basic dimensions and item pool of the questionnaire were deter-mined through group discussion,Delphi expert consultation and pre-investigation.In order to revise the ques-tionnaire,437 nurses from 10 tertiary hospitals in Jiangsu Province were conveniently selected for investigation,and the reliability and validity of the questionnaire were tested according to the survey results.Results The nurses'knowl-edge,attitude and practice questionnaire on medication management for patients with dysphagia included 43 items in three dimensions.The three dimensions were analyzed by exploratory factors,and six common factors with characteristic roots>1 were extracted.Two factors were extracted from the knowledge dimension,and the cumulative variance contribution rate was 74.958%,One factor was extracted from the attitude dimen-sion,and the cumulative variance contribution rate was 77.655%.Three factors were extracted from the prac-tice dimension,and the cumulative variance contribution rate was 72.274%.The factor load of each item was 0.618-0.902,Cronbach's α coefficient of the total questionnaire was 0.949,and the test-retest reliability was 0.909.The overall content validity coefficient of the questionnaire was 0.922,and the content validity coeffi-cient for each item was 0.800-1.000.Conclusion The nurses'knowledge,attitude and practice questionnaire on medication management for patients with dysphagia developed in this study has good reliability and validi-ty,and could be used as an effective tool to evaluate the status quo of nurses'medication management for pa-tients with dysphagia.

16.
Artículo en Zh | WPRIM | ID: wpr-1030937

RESUMEN

ObjectiveThe human angiotensin converting enzyme2 (hACE2) transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus (Delta/Omicron) to angiotensin converting enzyme2 (ACE2). Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group, SARS-CoV-2 infection group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1, with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice, detect the virus titer of the lung tissue of the mice, and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro, with median inhibitory concentration (IC50) of 526.3 mg·L-1 and 653.0 mg·L-1, respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT, Omicron, and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died, while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1 could reduce the mortality of mice, significantly lower the virus titer in the lung tissue of mice (P<0.05), and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However, its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.

17.
Artículo en Zh | WPRIM | ID: wpr-1030938

RESUMEN

ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group, model group, Tamiflu group, and BD-77 groups of 75 and 37.5 g·L-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group, model group, chloroquine phosphate group, and BD-77 groups of 75, 37.5, 18.75, and 9.375 g·L-1, with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect related inflammatory factors in lung tissue, and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group, the lung index of mice in each infection group was significantly increased (P<0.01), and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α) in the lung tissue of mice infected with human coronavirus 229E were all significantly increased (P<0.01). BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 (P<0.05, P<0.01), cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 (P<0.01), and lower the contents of IL-6, IL-10, and TNF-α in the lung tissue of mice infected with human coronavirus 229E (P<0.01). Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway, TNF signaling pathway, NOD-like signaling pathway, IL-17 signaling pathway, Forkhead box protein O (FoxO) signaling pathway, transforming growth factor-β (TGF-β) signaling pathway, and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism, enhancing the immune function of the host, and attenuating inflammatory responses.

18.
Artículo en Zh | WPRIM | ID: wpr-1036228

RESUMEN

ObjectiveTo evaluate the effectiveness of Lutongning granules in the treatment of trigeminal neuralgia in animal models and study its mechanism of action, so as to provide laboratory data support for the clinical application of Lutongning granules and precise treatment. MethodMale SD rats were randomly divided into normal group, model group, carbamazepine group (0.06 g·kg-1·d-1), high-dose Lutongning group (2.70 g·kg-1·d-1), and low-dose Lutongning group (1.35 g·kg-1·d-1) according to the stratified basic mechanical pain thresholds, with 10 rats in each group. A trigeminal neuralgia model of rats was prepared by injecting 30% talc suspension into the infraorbital foramen area of the rat. The drug groups were administered 10 mL·kg-1 of drugs by gavage after 2 h of modeling. The normal group and the model group were administered distilled water by gavage under the same conditions once a day for 10 consecutive days. Von Frey brushes were used to determine the mechanical pain threshold of rats. A fully automated blood and body fluid analyzer was employed to detect the blood routine of rats. Hematoxylin and eosin (HE) staining was utilized to detect the pathological changes in the trigeminal ganglion and medulla oblongata tissue. Transmission electron microscopy was used to scan the ultrastructure of the medulla oblongata tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, neuropeptide substance P, and β-endorphins (β-EP) in the serum of rats, and Western blot was used to detect the protein expression levels of IL-1β, purinergic receptor P2X7 (P2X7R), and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK). ResultCompared with that in the normal group, the pain threshold of rats in the model group was significantly lower (P<0.01). The absolute value of neutrophils (NEUT#) and the percentage of neutrophils (NEUT) were significantly improved, and the percentage of lymphocytes (LYMPH) was significantly reduced (P<0.01). The serum levels of IL-1, IL-6, IL-8, and TNF-α were significantly increased (P<0.01). SP content in brain tissue was significantly increased, and β-EP content was significantly decreased (P<0.01). The relative protein expression of IL-1β, P2X7R, and p-p38 MAPK was significantly increased (P<0.05). HE staining and transmission electron microscopy results of medulla oblongata tissue revealed neuronal degeneration, mild proliferation of microglial cells, reduction in the number of myelinated nerves, and obvious demyelination. The trigeminal nerve fibers of rats were disarranged, and some nerve fibers showed vacuolization. Axons were swollen, and Schwann cells proliferated. Demyelination was observed. Compared with the model group, each administration group significantly increased the pain threshold of rats (P<0.05, P<0.01), reduced NEUT# and NEUT, and elevated LYMPH (P<0.05, P<0.01). The administration group significantly decreased the levels of IL-1, IL-6, IL-8, and TNF-α in serum and SP in brain tissue (P<0.01) and increased the level of β-EP (P<0.01). They significantly down-regulated the protein expression of IL-1β, P2X7R, and p-p38 MAPK(P<0.05, P<0.01) and significantly ameliorated the pathological changes in medulla oblongata tissue and trigeminal nerves of rats. ConclusionLutongning Granules had significant therapeutic effects on trigeminal neuralgia induced by injection of talc into the infraorbital foramen of model rats, and the mechanism may be related to amelioration of P2X7R-mediated neuroinflammation and inhibition of demyelination of myelinated nerves.

19.
Chinese Journal of Neuromedicine ; (12): 374-381, 2023.
Artículo en Zh | WPRIM | ID: wpr-1035824

RESUMEN

Objective:To summarize the electrophysiological characteristics of neuronal intranuclear inclusion disease (NIID) and explore the value of electrophysiological examination in NIID auxiliary diagnosis.Methods:Twenty NIID patients diagnosed by pathological biopsy and genetic confirmation (15 were symptomatic, 5 were asymptomatic), admitted to Department of Neurology, Affiliated Hospital of Xuzhou Medical University from February 2020 to June 2022 were chosen. Peripheral motor/sensory nerve conduction, needle electromyography, F wave, repetitive electrical stimulation, skin sympathetic reflex (SSR), and tremor were analyzed. Peripheral nerve conduction and SSR parameters were compared between 15 patients with symptomatic NIID (symptomatic NIID group) and 11 age- and gender-matched normal control subjects (control group).Results:(1) All 15 patients with symptomatic NIID were with abnormal electrophysiological findings: 14 patients had abnormal peripheral nerve conduction, including 14 with slowed motor nerve conduction velocity (MCV), 4 with reduced composite muscle action potential (cMAP) wave amplitude, 12 with slowed sensory nerve conduction velocity (SCV), and 3 with reduced sensory nerve action potential (sNAP) wave amplitude, and overall slowed nerve conduction velocity and relatively preserved wave amplitude were noted; 4 patients had neurogenic lesions by needle electromyography; 13 patients had prolonged F-wave latency at varied degrees; 12 showed abnormal SSR; 4 exhibited synchronous tremor from 4.0 to 7.5 Hz. (2) In 5 patients with asymptomatic NIID, 3 had abnormal peripheral nerve conduction, including 3 with slowed MCV, 2 with slowed SCV, and 1 with reduced sNAP wave amplitude; 3 showed abnormal SSR. (3) Significant differences in MCV and SCV, some cMAP and sNAP amplitudes, and SSR latency and amplitude were noted in nerves of the upper and lower extremities between the symptomatic NIID group and control group ( P<0.05). Conclusion:Peripheral nerve damages are common in patients with NIID, especially myelin damage and autonomic nerve injury, and some patients may have electrophysiological abnormalities before clinical symptoms; therefore, peripheral nerve conduction and SSR can be recommended as auxiliary screening tools for NIID.

20.
Artículo en Zh | WPRIM | ID: wpr-1018250

RESUMEN

Objective:This study aims to investigate the effects of Zhibao Sanbian Pills on learning and memory ability and explore its mechanism.Methods:Cognitive decline and memory impairment in mice was induced by scopolamine. Morris water maze test, platform jumping test and dark avoidance test were used to evaluate the learning and memory ability of mice. TCMSP, TCMID database and literature search were used to search the chemical components of Zhibao Sanbian Pills. The potential active components were screened through ADMETlab 2.0. The targets were predicted by Swiss Target Prediction. GO function and KEGG pathway enrichment analysis were conducted through the Metascape database, and a PPI network was constructed for MCODE module analysis.Results:Compared with the model group, the latency of water maze test in the high-dose group of Zhibao Sanbian Pills was shortened ( P<0.05), and the time of platform quadrant and the number of crossing increased ( P<0.05). 863 active components and 401 potential targets of Zhibao Sanbian Pills were collected. The enrichment analysis of MCODE, GO and KEGG pathways found that the action pathways of Zhibao Sanbian Pills to improve cognitive impairment involve neuroactive ligand receptor pathway, calcium signal pathway, Rap1 signal pathway, PI3K-Akt signal pathway, MAPK signal transduction pathway, 5-hydroxytryptamine receptor pathway, etc. Conclusion:Zhibao Sanbian Pills have the potential to improve the learning and memory ability of mice, which may be realized through MAPK signaling pathway and other neural related signaling pathways.

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