Identification of genes and pathways in human antigen-presenting cell subsets in response to polio vaccine by bioinformatical analysis.

BACKGROUND: Polio eradication has been achieved in the world except for three countries due to the widespread use of the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine. Following polio eradication, the IPV would be the only polio vaccine available. However, the mechanisms of the interactions between IPV and human antigen-presenting cells (APCs) remain largely unclear. METHODS: To investigate the involvement of the IPV in human monocytes, we downloaded the gene chip GSE44721 from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the GEO2R analysis tool. Functional and pathway enrichment analyses were performed for DEGs using the Metascape database. DEG-associated protein-protein-interactions (PPIs) were established by the Search Tool for the Retrieval of Interacting Genes website and visualized by Cytoscape. RESULTS: There were 240 DEGs (51 upregulated and 189 downregulated genes) identified from the GSE44721 data set, and they were significantly enriched in several biological processes, including antigen processing and presentation of lipid antigen via MHC class Ib, adaptive immune response, and response to interferon-gamma. One hundred thirty-six nodes were screened from the DEG PPI network. There were six significant hub proteins (WDR36, MRTO4, RPF2, PPAN, CD40, and BMS1) that regulated the IPV in human monocytes. CONCLUSIONS: In summary, using bioinformatical analysis, we have information for the immunization activated by the IPV in monocytes. Moreover, hormones and cytokines regulate the activation of APCs.

Role of phenol red in the stabilization of the Sabin type 2 inactivated polio vaccine at various pH values.

To analyze the effects of phenol red at various pH values on the Sabin type 2 inactivated polio vaccine (sIPV2), several biophysical techniques were used to evaluate the particle size and capsid protein for conformation. sIPV2's size was assessed via transmission electron microscopy and dynamic light scattering. The effects of various pH values (from 4.0 to 7.0) on the biophysical characters of sIPV2 particles in solution were determined by dynamic light scattering and zeta potential. The results clearly indicated that aggregation and instability occurred in the solution of sIPV2 particles at a pH of 6.0. Under similar conditions, by dynamic light scattering and zeta potential, the virus particles in solution showed more dispersion and were stable with the addition of 0.05 mM phenol red. According to circular dichroism and intrinsic tryptophan fluorescence data, it was observed that the secondary and tertiary structures of the sIPV2 particles were more stable with the protection of phenol red. At a pH below 6.0, the sIPV2 solution with phenol red had more D-antigen content, which was confirmed by enzyme-linked immunosorbent assay and rat experiments. These results strongly suggested that phenol red improved the pH stability of the sIPV2. The study indicated the potential of phenol red in preserving vaccine potency of the sIPV2 at various pH values.

Catalyst characteristics of the composite catalyst of Ru-Sn and Pd for hydrogenation of terephthalic acid.

1,4-Cyclohexanedimethanol (CHDM) is a premium polyester monomer. In this paper, a series of Ru- Sn/γ-Al2O3 and Pd/γ-Al2O3 bimetallic composite catalysts were prepared by the impregnation method. The effects of preparation conditions such as active components, preparation methods, and the ratio of Sn to Ru on the reaction activity of the catalysts were studied. The bimetallic composite catalysts show desirable properties including high surface area and high dispersion of active centers. Pd-based catalysts were found to be effective in the initial stage of benzene ring hydrogenation, while Ru-based catalysts were found effective in the subsequent stage of carboxyl group hydrogenation. The Ru-Sn bimetallic active center was predominantly located in the Ru-based catalysts. In addition, the effects of reaction parameters such as reaction temperature, pressure, and time on hydrogenation reactions were also examined. It was found that increasing reaction temperature had no significant effect on the conversion rate of PTA, but it did affect the yield of CHDM, initially increasing and then decreasing. Increasing the reaction pressure resulted in a gradual increase in the yield of CHDM, while the conversion rate of PTA remained unchanged. The composite catalyst with a Sn/Ru ratio of 0.5 demonstrated the best performance, achieving a CHDM conversion of 96.3% and a yield of 72.2%.

Anti-cancer activity of Marsdenialongise A, a new C21 steroidal glycoside isolated from Marsdenia longipes W.T. Wang (Apocynaceae).

C21 steroidal glycosides are a group of natural compounds with biological activities such as anti-cancer, anti-microbial, and anti-viral properties. In this study, we isolated and determined the structure of a new C21 steroidal glycoside, named Marsdenialongise A from Marsdenia longipes W.T. Wang, using nuclear magnetic resonance spectroscopy and mass spectra data. Marsdenialongise A is a derivative of tenacigenin B and was isolated for the first time from a plant. The inhibitory effect of Marsdenialongise A on cancer cells was evaluated through MTT and cell migration assays, cell cycle, and apoptosis analyses. The results of the MTT assay showed that Marsdenialongise A reduces the cell viability of cancer cells, with the AGS cell line being more sensitive than other cell lines, with an IC50 value of 5.69 µM (for 48 h of treatment). Marsdenialongise A also exhibited an ability to prevent the migration of cancer cells in AGS cells. Further analysis using flow cytometry has revealed that Marsdenialongise A is capable of inducing cell cycle arrest and apoptosis. The overexpression of reactive oxygen species (ROS) production induced by Marsdenialongise A can be considered a cause that leads to the influence on the cell cycle and apoptosis of cancer cells. Thus, Marsdenialongise A can be considered a potential anti-cancer agent.

Influence of Different Heater Structures on the Temperature Field of AlN Crystal Growth by Resistance Heating.

Based on the actual hot zone structure of an AlN crystal growth resistance furnace, the global numerical simulation on the heat transfer process in the AlN crystal growth was performed. The influence of different heater structures on the growth of AlN crystals was investigated. It was found that the top heater can effectively reduce the axial temperature gradient, and the side heater 2 has a similar effect on the axial gradient, but the effect feedback is slightly weaker. The axial temperature gradient tends to increase when the bottom heater is added to the furnace, and the adjustable range of the axial temperature gradient of the side 1 heater + bottom heater mode is the largest. Our work will provide important reference values for AlN crystal growth by the resistance method.

Structural and electronic properties of oxidized sodium clusters: A combined photoelectron and density functional study.

Oxygen-doped sodium cluster anions Na(n)O(2) (-) with n=41-148 have been studied by low temperature photoelectron spectroscopy and density functional theory (DFT), with a particular emphasis on those sizes where a spherical electron shell closing is expected. The experimental spectra are in good agreement with the electronic density of states of the DFT lowest energy structures. The cluster structures show segregation between an ionically bonded molecular unit located at the cluster surface and a metallic part. The DFT calculations reveal that each oxygen atom removes two electrons from the metallic electron gas in order to become an O(2-) dianion. A jellium model would therefore predict the electron shell closings to be shifted up by four sodium atoms with respect to pure Na(n) (-) cluster anions. The electron shell closings for Na(n)O(2) (-) are located at n=43, 61, 93, and 139, so the expected four-atom shift is observed only for the small clusters of up to n=61, while a two-atom shift is observed for the larger clusters. The DFT calculations explain this departure from jellium model predictions in terms of a structural transition in the ionically bonded molecular unit.

Progress and prospect of global vaccine research and development / 中国药科大学学报

@#Abstract: The emerging infectious diseases have become an important risk factor affecting human public health. Vaccination remains the most critical approach to the prevention and control of such diseases. Since the outbreak of the COVID-19 epidemic, lots of transformational basic innovative vaccine technologies and strategies have been developed. The third-generation vaccine technology represented by mRNA vaccine has gradually become a new approach to the research and development of vaccines. This paper introduces the characteristics of different vaccine technologies in recent years, and summarizes the latest research progress in current vaccine products based on different platforms, so as to provide experience and reference for future research and development of vaccines.

Association of polymorphisms of the acetyl-coA acetyltransferase 1 gene and the melatonin receptor 1B gene with the susceptibility to nonalcoholic fatty liver disease / 临床肝胆病杂志

ObjectiveTo investigate the association of the polymorphisms of the acetyl-CoA acetyltransferase 1 （ACAT1） gene and the melatonin receptor 1B （MTNR1B） gene with the susceptibility to nonalcoholic fatty liver disease （NAFLD）. MethodsA total of 164 healthy controls and 228 NAFLD patients were enrolled in this study. PCR and sequencing methods were used to determine the genotypes of the polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus， and fasting venous blood samples were collected for biochemical analysis. The t-test was used for comparison of normally distributed continuous data between groups， and the non-parametric Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. ResultsThere were no significant differences between the NAFLD group and the healthy control group in the genotype distribution of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus （all P>0.05）. The carriers of AA genotype at the rs1044925 locus of the ACAT1 gene had a significantly higher level of low-density lipoprotein than the carriers of C allele （Z=-2.08， P=0.04）， and the carriers of G allele at the rs10830963 locus of the MTNR1B gene had a significantly higher level of fasting blood glucose than the carriers of CC genotype （Z=-3.01， P<0.01）. ConclusionThe polymorphisms of the ACAT1 gene at the rs1044925 and rs1157651 loci and the MTNR1B gene at the rs10830963 locus were not associated with the susceptibility to NAFLD. The rs1044925 locus of the ACAT1 gene and the rs10830963 locus of the MTNR1B gene are associated with the levels of low-density lipoprotein and fasting blood glucose， respectively.

Serological analysis of anti-K and anti-Wra detected in patient treated with daratumumab: a case report / 中国输血杂志

【Objective】 To investigate the reasonable serological detection method by analyzing the characteristics of anti-K and anti-Wra from a patient who received treatment with daratumumab. 【Methods】 Unexpected antibody screening and identification were performed by saline method, polybrene, cardioagglutinin, dithiothreitol (DTT) treatment, trypsin treatment and papain treatment in the patient's plasma and acid elution solution. Heat elution test was detected after absorbing patient serum with K antigen negative red blood cells. The characteristics of antibodies were analyzed and their titer was continuously detected. Cross matching was performed after excluding interference of daratumumab. 【Results】 Anti-K and anti-Wra were detected in saline and polybrene in the patient's plasma. The patient's elution solution contained daratumumab. DTT or trypsin treatment excluded interference of daratumumab but papain treatment did not. DTT treatment destroyed K antigen and missed the detection of IgG antibodies in the Kell system. Trypsin treatment did not affect K antigen and can detect IgG antibodies of Kell system(anti-k)in the serum of the patient treated with daratumumab. Anti K was IgM and the titer was 4 by saline method and it decreased to no agglutination in room temperature after 39 days. Anti-Wra was IgG and the titer by polybrene method was 4, and it decreased to 1 after 39 days. After 76 days, neither anti-K nor anti-Wra could be detected. Transfusions of K and Wra antigen negative red blood cells were safe and effective. 【Conclusion】 DTT treatment can exclude interference of daratumumab, but attention should be paid to missed detection of anti-K. To avoid interference of daratumumab and identify unexpected antibody, multiple methods such as DTT treatment, polybrene and trypsin treatment in combination are recommended.

Application of athletic training in the field for university students / Aplicação do treinamento esportivo em atletismo de campo para universitários / Aplicación del entrenamiento deportivo en el atletismo de campo para estudiantes universitarios

ABSTRACT Introduction There was a delay in China for the implementation of athletic physical training, often opting for technical and repetitive movements in their teaching method, resulting in an unsatisfactory didactic model. Objective Innovate physical training technology for teaching athletics in colleges and universities. Methods 80 students in two college and university athletics sports classes were submitted to two weekly athletics classes lasting 60 minutes. This paper measured and collected data before and after the battery of exercises, comparing the results pertinent to the group's physical fitness. All training lasted eight weeks. After this period, the relevant indices were measured again, ranked, and compared. Results The research shows that physical training can improve students' athletic performance in different grades, and the effect of athletic gain in students with lower initial performance is more significant. At the same time, strengthening physical training can effectively improve the basal performance of athletics and reduce the occurrence of sports injuries, ensuring the safety of the sports experienced. Conclusion Physical training can promote positive performance in athletics, deserving further research to popularize the implementation of athletic training in athletics for colleges and universities. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução Houve um atraso na China para a implementação do treino físico atlético, muitas vezes optando por movimentos técnicos e repetitivos em seu método de ensino, resultando num modelo didático insatisfatório. Objetivo Inovar a tecnologia de treinamento físico do ensino de atletismo em faculdades e universidades. Métodos 80 alunos em duas aulas de esportes de atletismo de Faculdades e universidades foram submetidos à duas aulas semanais de atletismo com duração de 60 minutos, este artigo mediu e coletou os dados antes e após a bateria de exercícios, comparando os resultados pertinentes à aptidão física do grupo. Todo o treinamento durou oito semanas. Após este período, os índices relevantes foram medidos novamente, classificados e comparados. Resultados A pesquisa mostra que o treinamento físico pode melhorar o desempenho atlético dos alunos em diferentes séries, e o efeito de ganho esportivo em alunos com menor desempenho inicial é mais significativo. Ao mesmo tempo, o fortalecimento do treinamento físico pode melhorar efetivamente o desempenho basal do atletismo e reduzir a ocorrência de lesões esportivas, garantindo a segurança dos esportes experenciados. Conclusão O treinamento físico pode promover rendimento positivo nos esportes de atletismo, merecendo mais pesquisas afim de popularizar a implementação do treinamento esportivo em atletismo para as Faculdades e universidades. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción En China se ha producido un retraso en la implantación del entrenamiento físico atlético, optando a menudo por movimientos técnicos y repetitivos en su método de enseñanza, lo que ha dado lugar a un modelo didáctico insatisfactorio. Objetivo Innovar la tecnología de entrenamiento físico de la enseñanza del atletismo en colegios y universidades. Métodos 80 estudiantes de dos clases de deportes de atletismo de la universidad fueron sometidos a dos clases semanales de atletismo de 60 minutos de duración, este trabajo midió y recogió los datos antes y después de la batería de ejercicios, comparando los resultados pertinentes a la aptitud física del grupo. La formación completa duró ocho semanas. Tras este periodo, se volvieron a medir los índices pertinentes, se clasificaron y se compararon. Resultados La investigación muestra que el entrenamiento físico puede mejorar el rendimiento deportivo de los estudiantes en diferentes grados, y el efecto de la ganancia deportiva en los estudiantes con menor rendimiento inicial es más significativo. Al mismo tiempo, el fortalecimiento del entrenamiento físico puede mejorar eficazmente el rendimiento basal del atletismo y reducir la aparición de lesiones deportivas, garantizando la seguridad de los deportistas experimentados. Conclusión El entrenamiento físico puede promover un rendimiento positivo en los deportes de atletismo, mereciendo una mayor investigación con el fin de popularizar la implementación del entrenamiento en el atletismo para los colegios y universidades. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Text analysis of China′s medical science and technology achievement transformation policy from the perspective of policy tools / 中华医学科研管理杂志

Objective:To understand the status of medical science and technology achievement transformation policies in application, this study conducted a descriptive statistical analysis of the collected relevant policy texts according to type, time, and publication sector. On this basis, the X-Y two-dimensional analysis framework of policy texts is constructed using the dual dimensions of Howlett and Ramesh′s policy tool classification and policy development to classify policies into 3 categories: mandatory tools, voluntary tools, and hybrid tools, and to quantify the policy texts on the transformation of medical science and technology achievements, analyze the policy support received in the transformation of medical science and technology achievements and the policy obstacles in the transformation of achievements in China. Finally, this study was aiming to propose targeted countermeasure suggestions.Methods:The texts of medical achievement transformation policies were collected through the official websites of the State Council and the Ministry of Science and Technology, and combined with relevant literature. Research methods such as literature research method and quantitative and qualitative analysis method were applied to conduct the study. The policy samples were coded and organized, and two-dimensional analysis was conducted through the constructed X-Y two-dimensional analysis framework. The texts were quantitatively analyzed through a combination of quantitative and qualitative methods.Results:The results of the analysis of the coded data revealed that the current mandatory tools of China′s medical science and technology achievement transformation policy account for a relatively high proportion, and the use of voluntary tools still needed to be further improved. The use of various policy tools was uneven. The internal structure of various policy tools was also uneven, and there was still room for improvement.Conclusions:Through qualitative and quantitative analysis of the results of the application of medical science and technology achievement transformation policy in China, this paper puts forward 3 countermeasure suggestions: firstly, in the stage of policy strengthening and implementation, the implementation path and scheme of policy tools need to be refined so that the policy can realize implementation. Secondly, the balanced development of various policy tools, the coordination of policy formulation and implementation, the balanced role of mandatory tools, hybrid tools and voluntary tools, and the establishment of a smooth policy system for the transformation of medical science and technology results on this basis to improve the effectiveness of the policy. Thirdly, improve the internal orientation and evaluation mechanism of medical institutions to motivate medical institutions and medical personnel to carry out scientific and technological innovation and transformation work.

Effect and mechanism of microRNA-101 on proliferation, apoptosis and invasion of pancreatic cancer PANC1 cells / 中华胰腺病杂志

Objective:To investigate the effect of microRNA-101 (miR-101) on proliferation, apoptosis and invasion of PANC1 cells of pancreatic cancer and its potential mechanism.Methods:PANC1 cells in logarithmic growth period were divided into 5 groups, including transfected miRNA mimic negative control group (mimic-NC group), transfected miRNA-101 mimic group (miR-101 mimic group), transfected miRNA inhibitor negative control group (inhibitor-NC group), and transfected miR-101 inhibitor group (miR-101 inhibitor group) besides control group. The relative expression level of miR-101 was detected by qRT-PCR, cell proliferation rate was determined by MTT assay, cell apoptosis rate was detected by flow cytometry, and cell invasion ability was detected by Transwell assay. The relative expression levels of IL-6, JAK2, p-JAK2, STAT3 and p-STAT3 mRNA and proteins were detected by qRT-PCR and Western blot. The targeting relationship between miR-101 and IL-6 was detected by dual luciferase reporter gene method.Results:After 48 h of transfection, the expression levels of miR-101 in PANC1 cells in control group, mimic-NC group, miR-101 mimic group, inhibitor-NC group and miR-101 inhibitor group were 1.98±0.12, 2.01±0.18, 6.73±0.23, 2.16±0.22 and 1.34±0.13; the proliferation rates were (32.75±2.43)%, (33.17±2.77)%, (15.68±1.17)%, (31.57±2.65)% and (45.75±3.16)%, respectively; the apoptosis rates were (3.82±0.57) %, (3.54±0.55)%, (28.61±0.78)%, (3.57±0.63)% and (1.03±0.62) %, respectively; the number of penetrating cells was (125.82±3.55), (132.17±4.28), (58.83±3.24), (128.77±5.06), (248.42±5.64)/high power field, respectively. The expression level of miR-101 and apoptosis rate in miR-101 mimic group were significantly higher than those in control group and mimic-NC group, and the proliferation rate and the number of transmembrane cells were significantly lower than those in control group and mimic-NC group. The expression level of miR-101 and apoptosis rate in miR-101 inhibitor group were significantly lower than those in control group, inhibitor-NC group and miR-101 mimic group, and the proliferation rate and the number of transmembrane cells were significantly higher than those in control group, inhibitor-NC group and miR-101 mimic group. The expression levels of IL-6, JAK2, STAT3 mRNA and protein in PANC1 cells of miR-101 mimic group were significantly lower than those in control group and mimic-NC group, while those in miR-101 inhibitor group were significantly higher than those in control group, miR-101 mimic group and inhibitor-NC group. The differences above were statistically significant ( all P value <0.001). Dual luciferase reporter gene assay showed that miR-101 could target IL-6. Conclusions:miR-101 can inhibit the proliferation and invasion of pancreatic cancer cells and promote their apoptosis, possibly through the regulation of IL-6/JAK2/STAT3 signaling pathway.

Transcriptome analysis of checkpoint kinase 2 in clear cell renal cell carcinoma / 现代泌尿外科杂志

【Objective】 To explore the expression of checkpoint kinase 2 (CHEK2) in clear cell renal cell carcinoma (ccRCC), its association with the clinicopathological features and prognosis, and to predict its relevant molecular signaling pathways and biological functions. 【Methods】 The gene expression data, phenotype data, and corresponding survival information of ccRCC patients were downloaded from TCGA database. The optimal cutoff value of CHEK2 was determined with the "survminer" package. The patients were divided into low and high expression groups, and the association between CHEK2 expression and clinicopathological features was analyzed. The correlation between CHEK2 expression and ccRCC prognosis was evaluated with univariate and multivariate Cox proportional hazard models. The changes of cell signaling pathways involved in different CHEK2 expression levels were explored with gene set variation analysis (GSVA). The correlation between CHEK2 and immune cell infiltration as well as immune checkpoint molecular expression was analyzed. 【Results】 CHEK2 expression was significantly higher in ccRCC tissues than in normal tissues (P<0.01). Higher level of CHEK2 was significantly associated with higher T stage of ccRCC (P<0.01). Kaplan-Meier analysis showed overall survival (OS) of patients with high CHEK2 expression were notably decreased (P<0.001). Univariate and multivariate analyses revealed CHEK2 expression as an independent risk factor of survival (HR=1.950, 95%CI: 1.490-2.570, P<0.001; HR=1.588, 95%CI: 1.185-2.127, P=0.002). GSVA showed that CHEK2 was involved in the following pathways: proximal tubule bicarbonate reclamation, propanoate metabolism, limonene and pinene degradation, fatty acid metabolism, primary immunodeficiency, systemic lupus erythematosus, p53 signaling pathway, homologous recombination, DNA replication and mismatch repair. Correlation analysis suggested that CHEK2 was associated with increased infiltration of multiple immune cells in ccRCC and upregulation of various immune checkpoint molecules. 【Conclusion】 The high level of CHEK2 in ccRCC is an independent predicting factor for poor prognosis. It is probably involved in regulating related events of tumor immune infiltration and may become a new target for ccRCC therapy.

Effect of electroacupuncture preconditioning on cellular immune function in patients undergoing thyroid surgery / 中华麻醉学杂志

Objective:To evaluate the effect of electroacupuncture preconditioning on cellular immune function in the patients undergoing thyroid surgery.Methods:Sixty-six patients of either sex, aged 30-55 yr, with body mass index of 18.5-23.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification ⅠorⅡ, were selected and divided into electroacupuncture preconditioning group (group D) and control group (group C) by a random number table method, with 33 cases in each group. Patients in both groups received combined intravenous-inhalational anesthesia. Before anesthesia induction, both Hegu and Neiguan acupoints were stimulated for 30 min using a continuous wave at a frequency of 2/100 Hz, and the stimulation intensity was subjected to patient tolerance in group D. Group C received sham electroacupuncture for 30 min without stimulation. Venous blood samples were collected at 30 min before anesthesia induction (T 0) and 12, 24 and 48 h after anesthesia (T 1-3). The percentages of T lymphocyte subsets (CD3 +, CD4 +, CD8 +, CD4 + /CD8 + ) and natural killer cells and concentrations of interleukin-6 and tumor necrosis factor-alpha in the serum were measured by flow cytometry. Results:Compared with group C, the percentage of CD3 +, CD4 + and natural killer cells and ratio of CD4 + /CD8 + were significantly increased at T 1, 2, and the concentrations of interleukin-6 and tumor necrosis factor-alpha in the serum were decreased at T 1-3 in group D ( P<0.05). Conclusions:Electroacupuncture preconditioning can improve cellular immune function in the patients undergoing thyroid surgery.

Effects of delayed ramelteon treatment on neurological function and tissue repair after cryogenic traumatic brain injury / 中国药理学通报

:Aim To study the effects of continuous dai¬ly administration of ramelteon starting at the subacute period of cryogenic traumatic brain injury (cTBI) on neurological function and brain tissue repair in mice. Methods Thirty male C57BL/6 mice were randomly divided into sham group, vehicle group and ramelteon treatment groups. The right sensory-motor cortex was damaged by pressing a copper probe precooled by liq¬uid nitrogen onto the skull. Ramelteon ( 10 nig 'kg-1 • d"1) was administered by gavage every day starting at different time points after cTBI (1 h, 1 d,3 d) until sacrifice on day 14. Beam walking test and open field test were used to evaluate the motor function. Toluidine blue staining was used to measure the infarct volume. Immunofluorescence was used to detect the expression of GAP-43 and synaptophysin in peri-infarct area. Mi¬croglia activation was detected using Iba-1. The area and thickness of glial scars were analyzed by detecting GFAP positive areas. Results All three treatment ( 1 h - 14 d, 1 - 14 d, and 3 - 14 d) significantly im¬proved cTBI induced motor dysfunction, reduced the infarct volume, elevated the expression of GAP -43 and synaptophysin, and decreased the area and thick¬ness of glial scar and microglia activation. In addition, all ramelteon treatment groups had similar effects on the above indexes. Conclusions Delayed ramelteon treatment can improve neurological dysfunction after cTBI,and the therapeutic time window can be delayed for up to three days after cTBI. Inhibiting glial scar formation and microglia activation, and promoting ax- onal regeneration and synaptogenesis may contribute to the beneficial effects of ramelteon.

Mechanism of glycyrrhetinic acid on inhibiting malignant biological behaviors of melanoma by Wnt / β - catenin pathways / 安徽医科大学学报

Objective @#To explore the possible mechanism of glycyrrhetinic acid on inhibiting malignant biological behaviors of melanoma by Wnt / β-catenin pathways．@*Methods@#The melanoma cells B16-F10 were selected as the research objects．The concentration gradient tests (0，1，2，4 μmol /L) were conducted by MTT．The cells given cisplatin intervention was enrolled as positive controls．The cells invasion and migration were detected by Transwell chamber assay．The expression levels of Wnt / β-catenin pathway proteins，invasion and migration related proteins (MMP-2，MMP-9) in B16-F10 cells were detected by Wester blot．The xenograft models of nude mice were constructed，and they were divided into control group (without drugs treatment) and glycyrrhetinic acid group (40 mg / kg) ．The growth of tumor tissues，and expression levels of Wnt / β-catenin pathway proteins，invasion and migration related proteins were observed. @*Results @#MTT results showed that glycyrrhetic acid could inhibit the proliferation of B16-F10 cells in a concentration-dependent manner．The inhibition effect of glycyrrhetic acid ( ≥2 μmol /L) was significant on the proliferation of B16-F10 cells (P ＜0. 05) ．The results of Transwell chamber assay showed that compared with control group，invasion and migration abilities of B16-F10 cells were significantly reduced after treatment with glycyrrhetinic acid (2，4 μmol /L) (P ＜0. 05) ．Wester blot results showed that compared with those without glycyrrhetinic acid treatment，expression levels of MMP-9 ，MMP-2，Wnt1 and β-catenin protein in B16- F10 cells significantly decreased after treatment with glycyrrhetinic acid (2，4 μmol /L) (P＜0. 05) ．The results of tumor-bearing assay showed that compared with control group ，weight and volume of tumors significantly decreased in glycyrrhetinic acid group，and expression levels of Wnt1 ，β-catenin，MMP-9 and MMP-2 proteins also significantly decreased (P＜0. 05) ．@*Conclusion @#Glycyrrhetinic acid can significantly inhibit the malignant biological behaviors of melanoma in vitro and vivo．And its mechanism may be related to inhibiting the activation of Wnt / β-catenin signaling pathways.

The coronary heart disease of phlegm-stasis cementation syndrome in mini-swine based on platelet proteomics / 药学学报

Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.

Proteomics reveals the protective mechanism of salvianolate injection on early hyperacute myocardial infarction / 药学学报

The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.

Analysis and evaluation on Paeoniae Radix Alba from different cultivars by UPLC-Q-TOF-MS and HPLC / 中国中药杂志

In this study, an established ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method was combined with multivariate statistical analysis to investigate the commonality and difference of main chemical components in the medicinal parts of Paeonia lactiflora from different cultivars; in addition, a high performance liquid chromatography(HPLC) method was established to simultaneously determine the content of eight active components in Paeoniae Radix Alba. Non-targeted analysis was carried out by UPLC-Q-TOF-MS on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 μm) column with a gradient elution of 0.1% aqueous formic acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 0.2 mL·min~(-1). The column temperature was 30 ℃, and an electrospray ionization source was used to acquire mass spectrometry data in positive and negative ion modes. According to the accurate molecular weight and fragment ion information provided by multi-stage mass spectrometry and by comparison with reference substances and literature reports, thirty-six identical components were identified in Paeoniae Radix Alba from different cultivars with positive and negative ion modes. In the negative ion mode, two groups of samples were well separated; specifically, seventeen components with significant differences in content were screened and identified, and one component unique in "Bobaishao" was obtained. Quantitative analysis was conducted by high-performance liquid chromatography(HPLC) on an Agilent HC-C_(18)(4.6 mm×250 mm, 5 μm) column with a gradient elution of 0.1% aqueous phosphoric acid(A)-acetonitrile(B) as the mobile phase at a flow rate of 1.0 mL·min~(-1). The column temperature was 30 ℃ and the detection wavelength was at 230 nm. An HPLC method was developed for the simultaneous determination of eight active components(gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, galloylpaeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoyl-paeoniflorin) in Paeoniae Radix Albaa from different cultivars. Satisfactory linearity was achieved within the investigated linear ranges and with fine coefficients(r>0.999 0), and the methodological investigation showed that the method had good precision, repeatability and stability. The mean recoveries were 90.61% to 101.7% with RSD of 0.12% to 3.6%(n=6). UPLC-Q-OF-MS provided a rapid and efficient qualitative analytical method for the identification of the chemical components in Paeoniae Radix Alba, and the developed HPLC method was simple, rapid and accurate, which could provide a scientific basis for the evaluation of the germplasm resources and herbal quality of Paeoniae Radix Alba from different cultivars.

Pre-operative prognostic nutritional index as a predictive factor for prognosis in non-metastatic renal cell carcinoma treated with surgery / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the implications of the prognostic nutrition index (PNI) in non-metastatic renal cell carcinoma (RCC) patients treated with surgery and to compare it with other hematological biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune inflammation index (SII).@*METHODS@#A cohort of 328 non-metastatic RCC patients who received surgical treatment between 2010 and 2012 at Peking University First Hospital was analyzed retrospectively. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values of the hematological biomarkers. The Youden index was maximum for PNI was value of 47.3. So we divided the patients into two groups (PNI≤ 47. 3 and >47. 3) for further analysis. Categorical variables [age, gender, body mass index (BMI), surgery type, histological subtype, necrosis, pathological T stage and tumor grade] were compared using the Chi-square test and Student' s t test. The association of the biomarkers with overall survival (OS) and disease-free survival (DFS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model.@*RESULTS@#According to the maximum Youden index of ROC curve, the best cut-off value of PNI is 47. 3. Low level of PNI was significantly associated with older age, lower BMI and higher tumor pathological T stage (P < 0.05). Kaplan-Meier univariate analysis showed that lower PNI was significantly correlated with poor OS and DFS (P < 0.05). In addition, older age, lower BMI, tumor necrosis, higher tumor pathological T stage and Fuhrman grade were significantly correlated with poor OS (P < 0.05). Cox multivariate analysis showed that among the four hematological indexes, only PNI was an independent factor significantly associated with OS, whether as a continuous variable (HR=0.9, 95%CI=0.828-0.978, P=0.013) or a classified variable (HR=2.397, 95%CI=1.061-5.418, P=0.036).@*CONCLUSION@#Low PNI was a significant predictor for advanced pathological T stage, decreased OS, or DFS in non-metastatic RCC patients treated with surgery. In addition, PNI was superior to the other hematological biomar-kers as a useful tool for predicting prognosis of RCC in our study. It should be externally validated in future research before the PNI can be used widely as a predictor of RCC patients undergoing nephrectomy.