[摘 要] 目的：探究牛蒡子苷元（ARC）通过调控Notch/Hes-1信号通路对口腔鳞状细胞癌（OSCC）HSC-3细胞增殖、凋亡和侵袭的影响及其机制。方法：使用不同质量浓度的ARC处理人HSC-3细胞，CCK-8法检测ARC对细胞增殖活力的影响，以选择适宜的药物浓度。将HSC-3细胞分为对照组、ARC-L组（10 mg/L ARC）、ARC-M组（20 mg/L ARC）、ARC-H组（40 mg/L ARC）和ARC-H+Jagged1/FC组（40 mg/L ARC+1.2 μg/mL Jagged1/FC）。采用EdU法检测细胞增殖能力，划痕愈合实验、Transwell实验和流式细胞术分别检测细胞的迁移、侵袭能力及细胞周期和细胞凋亡率，WB法检测增殖（c-Myc、cyclin D1）、凋亡（BAX、Bcl-2、survivin）、EMT（E-cadherin、vimentin、Snail）及Notch/Hes-1通路（Notch 1、Hes-1、NICD）相关蛋白的表达水平。结果：与0 mg/L相比，10~80 mg/L的ARC均能显著降低HSC-3细胞增殖活力（均P<0.05）。与对照组相比，ARC-L组、ARC-M组和ARC-H组HSC-3细胞EdU阳性率、划痕愈合率、侵袭细胞数、S期和G2/M期细胞占比及c-Myc、cyclin D1、Bcl-2、survivin、vimentin、Snail、Notch 1、Hes-1和NICD蛋白表达均显著降低（均P<0.05），细胞凋亡率、G0/G1期细胞占比及BAX、E-cadherin的蛋白表达均显著升高（均P<0.05），且呈浓度梯度依赖性。同时使用Notch激动剂Jagged1/FC，则可部分逆转ARC对HSC-3细胞增殖、迁移、侵袭、凋亡及相关蛋白表达的作用（均P<0.05）。结论：ARC可能通过抑制Notch/Hes-1信号通路抑制OSCC细胞HSC-3增殖和侵袭并促进细胞凋亡。

Objective To evaluate the differences in chemical composition and pharmacological effects between Angelica-Astragalus medicine pair decoction(DGD)and traditional decotion,and to provide a reference for the rational clinical application of Danggui Buxue decoction.Methods With the two comparison methods of unified and non-uniform raw material source batches,we set up different sample groups,established characteristic maps by HPLC,and evaluated the chemical components based on the similarity of characteristic maps,component types,index component content,common peak area,and other factors.The efficacy of the drug was evaluated in the hemorrhagic blood deficiency model mice.Results ①The similarity of the feature map between the DGD and TD was high(similarity was greater than 0.87).②The number of chromatographic peaks was inconsistent.Traditional decoction from self-purchased decoction pieces,or traditional decoction-Factory A decoction pieces had a total of 12 chromatographic peaks each.The DGD of Factory A had a total of 15 chromatographic peaks.There were 10 chromatographic peaks in the DGD of Factory B.③The contents of ferulic acid and calycosin 7-O-glucoside(CG)in DGD of Factory A were higher than those in traditional decoction(P<0.05,n=3).There was no significant difference between DGD and TD ferulic acid content in Factory B,but the content of CG was lower than that in traditional decoction(P<0.05).④The total area of common peaks in DGD was different from that in TD.The relative total ratios of the contents of the components in the self-purchased traditional decoction pieces,the traditional decoction pieces of Factory A,the formula granules of Factory A,and the formula granules of Factory B were 1.00,0.96,2.14,0.60,respectively.⑤Both DGD and traditional decoction could significantly promote the recovery of hemoglobin and red blood cells in hemorrhagic anemia model mice(P<0.01);Compared with the model control group,there was a significantly difference(P<0.05)except for the DGD group of Plant B.There was no significant difference between DGD and TD of Plant A,but there was a very significant difference between DGD and TD of Plant B(P<0.01).Conclusion Whether the raw material source batch is consistent or not,DGD and TD have certain differences in chemical composition.In terms of pharmacological effect,DGD,prepared from a unified batch of decoction pieces,has similar efficacy to traditional decoction in alleviating hemorrhagic anemia.There are certain differences in the pharmacological effects between DGD prepared from different batches of decoction pieces and traditional decoctions.The differences caused by the different preparation processes of the same source batch of prepared slices were compared,and the quality differences of the formula granules from different manufacturers were caused by the different source batches of prepared slices and different preparation processes,indicating the necessity and urgency of the country to formulate a unified quality standard for formula granules and related process specifications.

Objective This study aims to summarize the experience of constructing a national demonstration zone for in-tegrated prevention and control of chronic diseases in Dapeng New District,Shenzhen,in order to provide a reference for grassro-ots chronic disease management in various regions.Methods Employing literature review and case analysis and using material description and data analysis,the study summarized the experience of target management experience in a close-knit medical con-sortium and offered suggestions for building a chronic disease system.Results Through close-knit medical consortium and target management method,the primary medical resources in Shenzhen Dapeng New District were optimized,and multi-sectoral coopera-tion was facilitated.This resulted in an increase in the main index data of chronic disease prevention and control,with the propor-tion of primary diagnosis and treatment increasing from 31.69％to 57.29％.Additionally,the health literacy rate among resi-dents improved from 39.1％to 50.82％,and several assessments achieved the first place within the city.Conclusion Regions can establish a close-knit medical consortium to set common goals,guiding high-quality medical resources to the grassroots level.By employing target management,they can concentrate effects from various grassroots sectors to advance chronic disease manage-ment construction.

Intravenous thrombolysis is an effective treatment for acute ischemic stroke, but its benefits are time-dependent. The time from onset to intravenous thrombolysis is divided into onset-to-door time (ODT) and door-to-needle time (DNT). The former reflects pre-hospital delay, while the latter reflects in-hospital delay and can be controlled by stroke improvement plan. This article reviews the influence of DNT on clinical outcomes, the influencing factors of DNT and the stroke improvement plan to shorten DNT.

Objective:To implement the teaching activities for cultivating the four characteristics (innovation, development, integration, and ecology) and the four abilities (political ability, learning ability, cross-border ability, and driving force), and to provide a reference for improving the capability of service-based education in basic teaching organizations.Methods:The basic teaching organization in School of Basic Medical Sciences, Qiqihar Medical University, was selected for research, and the action research method and the focus group interview method were used to carry out characteristic teaching activities around the cultivation of the four characteristics and the four abilities. After the implementation of these activities, Sojump, a questionnaire platform, was used to conduct a survey among full-time and part-time teachers and teaching administrators, and the effect of each activity on the cultivation of the four characteristics and the four abilities was analyzed. The strategies to enhance abilities were improved based on the results of the above analyses. SPSS 25.0 software was used for data processing, and categorical data were expressed as frequency and percentage.Results:The data analysis showed that through cultivation of the four characteristics and the four abilities, each designed activity had a remarkable effect on improving the capability of service-based education in the basic teaching organization, with a mean value of 80.77%(63/78)- 91.03%(71/78), and only the activities centered on "integration" had a relatively low value of "obvious effect", which accounted for 64.10%(50/78).Conclusion:Under the guidance of the new concept of "New Medicine" and with the opportunity of capacity building, a series of teaching activities focusing on the four characteristics and the four abilities can effectively improve the capability of service-based education in basic teaching organizations in colleges and universities through targeted ability training.

Carotid atherosclerotic plaque rupture and thrombosis are the independent risk factors of acute ischemic cerebrovascular disease. Early identification of vulnerable plaques provides the evidence for early intervention in patients with asymptomatic carotid artery stenosis, and also helps to reduce the recurrence risk in patients with symptomatic carotid artery stenosis. This article focuses on comparing the advantages and limitations of the available clinical imaging methods in identifying vulnerable carotid artery plaque, and provides relevant prognostic indicators for patient risk stratification in clinical work.

Objective:To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development.Methods:In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old.Results:The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points.Conclusion:Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.

Objective:To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development.Methods:In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old.Results:The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points.Conclusion:Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.

Human coronavirus OC43 (HCoV-OC43) and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) belong to the β-coronavirus genus. Since the discovery in 1967, HCoV-OC43 has been continuously circulating in human population and has become one of the common seasonal respiratory viruses. SARS-CoV-2, which has a higher morbidity and fatality rate, appeared at the end of 2019, followed by the emergence of a variety of variants, and the transmission and infection capacity of SARS-CoV-2 has been enhanced. HCoV-OC43 may be similar to SARS-CoV-2 in terms of genomic structure and function, species evolution, epidemic characteristics and clinical manifestations. In this review, the epidemiology, genomics, phylogenetic evolution and other aspects of HCoV-OC43 and SARS-CoV-2 were analyzed. Such an analysis would be helpful to understand the association and differences between the two viruses, and provide reference for understanding the potential threats of HCoV-OC43.

Objective To observe the protective effect of polypyrimidine bundle-binding proteinrelated splicing factor (PSF) over-expression on RPE cell injury induced by advanced glycation end products (AGEs).Methods The human RPE cells cultured in vitro were divided into three groups:normal control group (N group),blank control group (N + AGEs group),empty vector control group (Vec + AGEs group),and PSF high expression group (PSF + AGEs).group).RPE cells in N group were routinely cultured;RPE cells in N + AGEs group were only transfected but did not introduce any exogenous genes combined with AGEs induction;Vec +AGEs group and PSF + AGEs group were transfected with pcDNA The empty vector or pcDNA-PSF eukaryotic expression plasmid was introduced into RPE cells and induced by AGEs.Except the N group,the other 3 groups of cells were transfected accordingly,and were stimulated with 150 μg/ml AGEs for 72 h after 24 h.HE staining and Hoechst 33258 staining were used to observe the effect of high PSF expression on the morphological changes of RPE cells;ROS level detection was used to analyze the effect of PSF high expression on the ROS expression of RPE cells induced by AGEs;MTT colorimetric method was used to detect the high PSF expression Effects on the viability of RPE cells;Western blot was used to detect the effects of different time and dose of PSF on the expression of heme oxygenase 1 (HO-1).Results HE staining and Hoechst 33258 staining observation showed that the cells in group N were full in shape,the nucleus was round,the cytoplasm was rich,and the staining was uniform;the cells in N + AGEs group and Vec + AGEs group were reduced in size,the eosinophilic staining was enhanced,and the nucleus was densely densely stained.Pyrolysis and even fragmentation;the morphology of cells in the PSF + AGEs group was still full,the cytoplasm staining was more uniform,and the nucleus staining was uniform.The results of MTT colorimetry showed that high expression of PSF can effectively improve the viability of RPE cells,but this effect can be effectively antagonized by ZnPP,and the difference is statistically significant (F=33.26,P＜0.05).DCFH-DA test results showed that compared with the N + AGEs group and Vec + AGEs group,the ROS production in PSF + AGEs group decreased,the difference was statistically significant (F=1 1.94,P＜0.05).Western blot analysis showed that PSF protein upregulated HO-1 expression in a time-and dose-dependent manner.The relative expression level of HO-1 at 24,48,and 72 h after PSF protein was significantly higher than that at 0 h,and the difference was statistically significant (F=164.91,P＜0.05).The relative expression level of HO-1 under the action of 0.1,0.5,1.0,1.5,and 2.0 μg PSF protein was significantly higher than 0.0 μg,and the difference was statistically significant (F=104.82,P＜0.05).Conclusion PSF may inhibit the production of ROS by up-regulating the expression of HO-1,thus protecting the RPE cells induced by AGEs.