OBJECTIVE To investigate and analyze the current management of drug clinical trial institutions in Jiangxi Province and the situation of undertaking drug clinical trials after the implementation of the filing system. METHODS A survey was conducted on 38 new institutions （obtained qualifications during the implementation of the filing system） and old institutions （obtained qualifications during the implementation of the recognition system） that had completed drug clinical trial institution qualification filing for more than one year in Jiangxi Province. The survey focused on the basic information of the institutions， the number of registered principal investigator （PI）， institutional hardware and information construction， personnel allocation and training， and drug registration clinical trials undertaken by the institutions. RESULTS Of 38 institutions surveyed， there were 22 general hospitals and 16 specialized hospitals； there were 24 old institutions and 14 new institutions. Whether in general hospitals or specialized hospitals， the old institutions were better than the new institutions in the number of approved beds， the number of outpatients， the number of inpatients， the number of specialties， and the number of PI； both old and new institutions had separate offices； all new institutions were set up with GCP pharmacy. The adoption of clinical trial management system in new institutions is significantly less than in old institutions. In the general hospital， both the number of full-time managers and the number of quality controllers in old institutions were significantly more than in the new institutions， while the opposite was true at the level of specialized hospitals. In terms of centralized training on GCP， new institutions were all better than the old ones. Whether in general hospitals or specialized hospitals， the number of drug registration clinical trial projects undertaken by new institutions was significantly less than that of old ones. CONCLUSIONS The new institutions are worse than the old institutions in comprehensive strength and information construction of hospitals， and the number of clinical trials undertaken by new institutions is also less than old institutions.

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective To investigate the clinical significance of combined cerebrospinal fluid(CSF)and routine blood parameter analysis in differentiating between multiple cerebral glioma(MCG)and primary central nervous system lymphoma(PCNSL).Methods We Rretrospectively analyzed the clinical data,CSF and routine blood indicators levels of 62 MCG patients and 56 PCNSL patients admitted to Beijing Tiantan Hospital,Capital Medical University from November 2017 to March 2023.Additionally,we assessed the diagnostic value of individual meaningful indicators as well as their combinations in distinguishing between MCG and PCNSL.Results The levels of CSF total cell count,CSF white cell count,CSF:pro,lactate,routine bloodperipheral neutrophil count,and neu-trophil percentage were significantly higher in the MCG group than in the PCNSL group(P<0.05);while the levels of CSF:Glu,CSF:cl,routine blood lymphocyte count,eosinophil,lymphocyte percentage,and eosinophil percent-age were significantly higher in the PCNSL group than in the MCG group(P<0.05).The AUCs of CSF cell count,CSF white cell count,CSF:pro,lactate,routine blood neutrophil count,neutrophil percentage for differentiating MCG from PCNSL were 0.900,0.899,0.797,0.867,0.828 and 0.772 respectively;sensitivities were 72.4%,77.6%,63.8%,67.2%,72.4%,82.8%,77.6%and 81%,with sensitivities of 97.1%,100%,88.2%,91.2%,88.2%,64.7%,100%and 94.1%,respectively.In addition,the combined detection of CSF total cell count,CSF white cell count,CSF:pro,routine blood neutrophil count and neutrophil percentage in CSF had an AUC of 0.919 for differentiating MCG from PCNSL,with a sensitivity and specificity of 77.6%and 100%,respectively.Conclusions Combined detection of CSF indicators including CSF total cell count,CSF white cell count,CSF:pro,along with routine blood markers such as neutrophil count and neutrophil percentage,holds significant clinical utility for differ-entiating between MCG and PCNSL.

Objective Based on the PDCA cycle theory,it explores the application mode of scenario simulation teaching method in clinical basic skills training.Methods The 96 students majoring in clinical medicine from the First Af-filiated Hospital of Harbin Medical University in 2019 were selected as the research objects,and the experimental group and the control group were set up respectively,with 48 students in each group,and skills training was car-ried out from March to December 2022.The control group was trained in the traditional way,and the experimental group was trained in the scenario simulation teaching method based on the PDCA cycle.The training effect and training satisfaction of the control group and the experimental group were compared and analyzed.Results In the sur-vey of the training effect of the students in the experimental group,the evaluation results of the basic clinical skills operation were higher than those in the control group,and the difference between the two groups was statistically significant(P＜0.01).In terms of the appropriate and safe operation mode,There was no significant difference be-tween the two groups(P＞0.05).In the training satisfaction survey,students in the experimental group were signifi-cantly more satisfied with the training than those students who are in the control group.The difference was statistical-ly significant(P＜0.01).Conclusion The application of scenario simulation teaching method based on PDCA cycle in clinical basic skills training helps to improve the quality of clinical basic skills training and student satisfaction.

Objective To investigate the effect of Cyclocarya paliurus(Batal.)lljinskaja polysaccharides on insulin resistance in type 2 diabetic rats by regulating glucose transporter 4(GLUT4)translocation in islet and liver.Methods High-fat diet combined with low-dose streptozotocin(35 mg·kg-1)to induce type 2 diabetes model,all the rats were randomly divided into model control group,Cyclocarya paliurus polysaccharides groups(5,10 g·kg-1)and metformin group(0.25 g·kg-1),and treated for eight weeks(n=9 in each group).Fasting glucose and lipid were determined.Histopathology of rat islet and liver were observed by hematoxylin and eosin staining.Protein expressions of phosphorylated phosphoinositide-3-kinase(p-PI3K),phosphorylated serine-threonine kinase 1(p-Akt1),and GLUT4 in islet were measured by immunohistochemistry staining.GLUT4 translocation in the islet and liver was detected by immunofluorescence.Results Compared with the model control group,the Cyclocarya paliurus polysaccharides group and metformin group had declined fasting glucose levels and increased high-density lipoprotein(P＜0.05).The structure of the islets and liver was relatively complete.The content of p-PI3K,p-Akt1 and GLUT4 in the islet increased(P＜0.05).GLUT4 translocation in the liver and islet enhanced(P＜0.05).Conclusions Cyclocarya paliurus polysaccharides alleviate glucose and lipid metabolism disorders.The mechanism may lay in it activating protein expressions of p-PI3K,p-Akt1,and GLUT4 in islet cells.GLUT4 translocation to the islet and liver cell membrane are increased to regulate peripheral islet resistance.

Background Improper settings of outdoor smoking points in public places may increase the risk of secondhand smoke exposure among the population. Conducting research on air pollution in and around smoking spots and related influencing factors can provide valuable insights for optimizing the setting of outdoor smoking points. Objective To investigate the influence of the number of smokers at outdoor smoking points and the distance on the diffusion characteristics of surrounding air pollutants, in order to optimize the setting of outdoor smoking points. Methods Surrounding the exhibition halls in the China International Import Expo (CIIE), two outdoor smoking points were randomly selected, one on the first floor (ground level) and the other on the second floor (16 m above ground), respectively. At 0, 3, 6, and 9 m from the smoking points in the same direction, validated portable air pollutant monitors were used to measure the real-time fine particulate matter (PM_2.5) and carbon dioxide (CO₂) concentrations for consecutive 5 d during the exhibition, as well as the environmental meteorological factors at 0 m with weather meters including wind speed, wind direction, and air pressure. An open outdoor atmospheric background sampling point was selected on each of the two floors to carry out parallel sampling. Simultaneously, the number of smokers at each smoking point were double recorded per minute. The relationships between the number of smokers, distance from the smoking points, and ambient PM_2.5 and CO₂ concentrations were evaluated by generalized additive regression models for time-series data after adjustment of confounders such as temperature, relative humidity, and wind speed. Results The median numbers of smokers at smoking points on the first and second floors were 6 [interquartile range (IQR): 3, 9] and 9 (IQR: 6, 13), respectively. Windless (wind speed <0.6 m·s⁻¹) occupied most of the time (85.9%) at both locations. The average concentration of ambient PM_2.5 at the smoking points (0 m) [mean ± standard deviation, (106±114) μg·m⁻³] was 4.2 times higher than that of the atmospheric background [(25±7) μg·m⁻³], the PM_2.5 concentration showed a gradient decline with the increase of distance from the smoking points, and the average PM_2.5 concentration at 9 m points [(35±22) μg·m⁻³] was close to the background level (1.4 times higher). The maximum concentration of CO₂ [(628±23) μmol·mol⁻¹] was observed at 0 m, and its average value was 1.3 times higher than that of the atmospheric background [(481±40) μmol·mol⁻¹], and there was no gradient decrease in CO₂ concentration with increasing distance at 0, 3, 6, and 9 m points. The regression analyses showed that, taking smoking point as the reference, every 3 m increase in distance was associated with a decrease of ambient PM_2.5 by 24.6 [95% confidence interval (95%CI): 23.5, 25.8] μg·m⁻³ (23.2%) and CO₂ by 54.1 (95%CI: 53.1, 55.1) μmol·mol⁻¹ (8.6%). Every one extra smoker at the smoking point was associated with an average increase of PM_2.5 and CO₂ by 2.0 (95%CI: 1.7, 2.8) μg·m⁻³ and 1.0 (95%CI: 0.7，1.2) μmol·mol⁻¹, respectively. The sensitivity analysis indicated that, under windless conditions, the concentrations of PM_2.5 and CO₂ at the smoking points were even higher but the decreasing and dispersion characteristics remained consistent. Conclusion Outdoor smoking points could significantly increase the PM_2.5 concentrations in the surrounding air and the risks of secondhand smoke exposure, despite of the noticeable decreasing trend with increasing distance. Considering the inevitable poor dispersion conditions such as windless and light wind, outdoor smoking points are recommended to be set at least 9 m or farther away from non-smoking areas.

Objective Based on the PDCA cycle theory,it explores the application mode of scenario simulation teaching method in clinical basic skills training.Methods The 96 students majoring in clinical medicine from the First Af-filiated Hospital of Harbin Medical University in 2019 were selected as the research objects,and the experimental group and the control group were set up respectively,with 48 students in each group,and skills training was car-ried out from March to December 2022.The control group was trained in the traditional way,and the experimental group was trained in the scenario simulation teaching method based on the PDCA cycle.The training effect and training satisfaction of the control group and the experimental group were compared and analyzed.Results In the sur-vey of the training effect of the students in the experimental group,the evaluation results of the basic clinical skills operation were higher than those in the control group,and the difference between the two groups was statistically significant(P＜0.01).In terms of the appropriate and safe operation mode,There was no significant difference be-tween the two groups(P＞0.05).In the training satisfaction survey,students in the experimental group were signifi-cantly more satisfied with the training than those students who are in the control group.The difference was statistical-ly significant(P＜0.01).Conclusion The application of scenario simulation teaching method based on PDCA cycle in clinical basic skills training helps to improve the quality of clinical basic skills training and student satisfaction.

Objective Based on the PDCA cycle theory,it explores the application mode of scenario simulation teaching method in clinical basic skills training.Methods The 96 students majoring in clinical medicine from the First Af-filiated Hospital of Harbin Medical University in 2019 were selected as the research objects,and the experimental group and the control group were set up respectively,with 48 students in each group,and skills training was car-ried out from March to December 2022.The control group was trained in the traditional way,and the experimental group was trained in the scenario simulation teaching method based on the PDCA cycle.The training effect and training satisfaction of the control group and the experimental group were compared and analyzed.Results In the sur-vey of the training effect of the students in the experimental group,the evaluation results of the basic clinical skills operation were higher than those in the control group,and the difference between the two groups was statistically significant(P＜0.01).In terms of the appropriate and safe operation mode,There was no significant difference be-tween the two groups(P＞0.05).In the training satisfaction survey,students in the experimental group were signifi-cantly more satisfied with the training than those students who are in the control group.The difference was statistical-ly significant(P＜0.01).Conclusion The application of scenario simulation teaching method based on PDCA cycle in clinical basic skills training helps to improve the quality of clinical basic skills training and student satisfaction.