[摘 要] 目的：探究β-半乳糖苷α-2-6唾液酸转移酶1（ST6GAL1）对结直肠癌（CRC）HCT116细胞糖酵解和迁移、侵袭的作用及可能的分子机制。方法：通过检索GEPIA2数据库，分析ST6GAL1在CRC患者和健康人群中的表达差异；WB法检测ST6GAL1在CRC细胞HCT116、SW480、Caco-2、HT29、LoVo和人正常结肠上皮细胞NCM460细胞中的表达差异；免疫组织化学法分析ST6GAL1在CRC组织和对应癌旁组织中的表达差异。通过慢病毒转染细胞的方法构建稳定敲低或过表达ST6GAL1的HCT116细胞，通过划痕愈合实验检测细胞迁移能力，Transwell实验检测细胞侵袭能力，WB法检测细胞糖酵解相关蛋白、Notch1受体胞内段（Notch1 ICD）以及PI3K/AKT/mTOR通路磷酸化水平，细胞免疫荧光实验观察Notch1 ICD表达水平和进入细胞核情况；加入Notch1受体激动剂Jagged1处理HCT116细胞，通过WB法检测糖酵解相关蛋白、Notch1 ICD表达水平以及PI3K/AKT/mTOR通路磷酸化水平。结果：ST6GAL1在CRC组织和细胞中均表达上调（均P < 0.05）。与对照组和过表达组相比，敲低ST6GAL1导致HCT116细胞内Notch1 ICD表达水平和PI3K/AKT/mTORC1磷酸化水平显著降低，细胞糖酵解相关蛋白表达水平降低，细胞迁移和侵袭能力减弱（均P < 0.05）；过表达ST6GAL1增加了HCT116细胞内Notch1 ICD表达水平并促进其进入细胞核，细胞糖酵解相关蛋白表达水平升高，细胞迁移和侵袭能力增强（均P < 0.05）。结论：ST6GAL1通过活化Notch1受体进而磷酸化激活PI3K/AKT/mTORC1通路，并增强CRC细胞糖酵解水平和迁移、侵袭能力。

In recent years, with the clinical application of minimally invasive surgical techniques and comprehensive preoperative treatment, the survival rate of locally advanced esophageal cancer has significantly improved. However, the treatment of metastatic esophagogastric cancer still relies mainly on systemic therapy, and immunotherapy combined with chemotherapy has become a first-line treatment option, prolonging the survival of patients with metastatic esophageal cancer. Oligometastatic esophageal cancer is expected to bring survival benefits through systemic therapy combined with local treatment. The 2024 European clinical practice guidelines for oligometastatic esophagogastric cancer have been officially released, which standardize the definition, diagnosis, and treatment of oligometastatic esophageal cancer for further prospective studies. The authors interpret this guideline, especially by reviewing the clinical evidence of oligometastatic esophageal squamous cell carcinoma, to provide reference for the diagnosis and treatment of oligometastatic esophageal cancer in China.

Objective To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in elderly hypertensive population. Methods Elderly physical examination population who received dual-energy bone mineral density examination and bone metabolic marker test in the hospital were selected from January 2021 to December 2024. According to whether they had hypertension and dual-energy bone mineral density results, the enrolled patients were divided into hypertension OP group (142 cases ), hypertension non-OP group (173 cases), non-hypertension OP group (102 cases) and non-hypertension non-OP group (100 cases). GNRI of all study subjects was measured. The correlation of GNRI and the occurrence of OP was explored by logistic regression analysis. The predictive efficiency of GNRI on the occurrence of OP was evaluated by receiver operating characteristic (ROC) curve. Results The BMD and GNRI in the hypertension group, and the non-hypertension OP group were significantly lower than those in the non-hypertension non-OP group (P<0.05). Compared with the hypertension non-OP group, the BMI, GNRI, BMD, and 25-OH Vit D in the hypertension OP group were significantly reduced (P<0.05) while the PTH level was significantly enhanced (P<0.05).logistic regression analysis showed that GNRI, 25-OH Vit D and PTH were closely related to OP in the elderly hypertensive population (P < 0.05). ROC curve analysis manifested that the AUC value of GNRI alone in predicting OP in elderly hypertensive population was 0.802, which was higher than that of 25-OH Vit D (AUC=0.723) and PTH (AUC=0.643). The AUC, sensitivity and specificity of combination of GNRI, 25-OH Vit D and PTH in predicting OP in elderly hypertensive population were 0.837, 66.20% and 86.13% (P<0.05). Conclusion GNRI is closely related to the occurrence of OP in elderly hypertensive population, and GNRI can be used as a potential indicator to assess the risk of OP.

Objective To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in elderly hypertensive population. Methods Elderly physical examination population who received dual-energy bone mineral density examination and bone metabolic marker test in the hospital were selected from January 2021 to December 2024. According to whether they had hypertension and dual-energy bone mineral density results, the enrolled patients were divided into hypertension OP group (142 cases ), hypertension non-OP group (173 cases), non-hypertension OP group (102 cases) and non-hypertension non-OP group (100 cases). GNRI of all study subjects was measured. The correlation of GNRI and the occurrence of OP was explored by logistic regression analysis. The predictive efficiency of GNRI on the occurrence of OP was evaluated by receiver operating characteristic (ROC) curve. Results The BMD and GNRI in the hypertension group, and the non-hypertension OP group were significantly lower than those in the non-hypertension non-OP group (P<0.05). Compared with the hypertension non-OP group, the BMI, GNRI, BMD, and 25-OH Vit D in the hypertension OP group were significantly reduced (P<0.05) while the PTH level was significantly enhanced (P<0.05).logistic regression analysis showed that GNRI, 25-OH Vit D and PTH were closely related to OP in the elderly hypertensive population (P < 0.05). ROC curve analysis manifested that the AUC value of GNRI alone in predicting OP in elderly hypertensive population was 0.802, which was higher than that of 25-OH Vit D (AUC=0.723) and PTH (AUC=0.643). The AUC, sensitivity and specificity of combination of GNRI, 25-OH Vit D and PTH in predicting OP in elderly hypertensive population were 0.837, 66.20% and 86.13% (P<0.05). Conclusion GNRI is closely related to the occurrence of OP in elderly hypertensive population, and GNRI can be used as a potential indicator to assess the risk of OP.

Objective To analyze the research status and trend of scarlet fever literature in China, and to provide reference for subsequent research. Methods Three major Chinese databases, CNKI, Wanfang, and VIP, as well as Web of Science English database, were used to search for literature related to scarlet fever from 2000 to 2023. Citespace6.2.R2 software was used to statistically analyze the number of publications, authors, institutions and journals, co-cited literature, keyword clustering, and other literature characteristics of the literature. Results From 2000 to 2023, a total of 1 011 Chinese literature were included in the three major Chinese databases. Since 2011, the number of publications had gradually increased, but in recent years, the number of publications had decreased. The organization with the most publications was the Shenyang Center for Disease Control and Prevention. The cluster analysis of key words mainly formed 9 cluster tags, and the high-frequency keywords mainly included epidemic characteristics, epidemiology, incidence rate, etc. A total of 84 English literature were included in the WOS database, with an overall upward trend in publication volume. The institution with the most publications was the China Center for Disease Control and Prevention, and the most frequently cited journal was ^“LANCET INFECT DIS^”.《Resurgence of scarlet fever in China: a 13-year population-based surveillance study》 was the most cited journal. After keyword cluster analysis, 9 cluster labels were mainly formed, and the keywords were mainly outbreak，Hong Kong, and Group A streptococcus. Conclusion Compared with the English literature, which mainly focuses on spatiotemporal aggregation, etiology and strain resistance, Chinese literature focuses more on epidemic surveillance, clinical features and quality nursing.

Objective In this study, a strain of colistin and tigecycline-resistant bacteria isolated in 2009 was analyzed, and the structure of drug-resistant plasmid and genetic environment were discussed, so as to provide basis for the prevention and control of multidrug-resistant bacteria. Methods A strain (GZ12244) with positive mcr and tet(M) was obtained by screening colistin and tigecycline resistance genes. Vitek-2 was used for strain identification, and the drug sensitivity test was carried out by broth dilution method. The molecular typing, drug resistance genes, insertion sequences, plasmid structure and genetic background were analyzed by genome-wide sequencing and bioinformatics. Results Strain GZ12244 is Klebsiella pneumoniae, which is resistant to colistin B, tigecycline, cefuroxime and tetracycline, and carries a variety of drug-resistant related genes such as mcr-1 and tet(M), and some of the drug-resistant genes with antibiotic efflux and antibiotic target change have amino acid substitution mutations. Mcr-1 and tet(M) coexist in a plasmid, and mcr-1 flanked by two insertion sequences ISApl1. There are insertion sequences such as IS15, IS1D and ISEc63 in the upstream and downstream of tet(M) gene. Conclusion Klebsiella pneumoniae GZ12244 is a multidrug-resistant strain. The drug-resistant gene exists in plasmid, and the mobile elements in upstream and downstream may spread the drug-resistant gene.

Objective To explore the research progress, research hotspot and development trend of tigecycline resistance based on the quantitative analysis and visualization function of CiteSpace. Methods The data were collected from 4,263 Chinese and English articles on tigecycline resistance in CNKI, Wanfang, VIP and Web of Science (WOS) databases from 2012 to 2022. CiteSpace 5.8.R3 software was used to analyze the cooperative network of authors, the cooperative network of countries and institutions, the total citation times of journals, and keywords included in the literature, to reveal the hotspots and trends of tigecycline resistance research. Results The number of articles published in English literature was higher than that in Chinese literature. China had the largest number of published documents, showing a significant international academic influence in this research field. Countries all over the world were concerned about the resistance of tigecycline, but Chinese literatures focused more on the clinical infection and prevention of tigecycline resistance, while English literatures placed special emphasis on the research about the drug resistance mechanism of tigecycline. Conclusion The research direction at home and abroad is basically the same, but the research focus has gradually shifted from the clinical treatment and monitoring of tigecycline to the molecular level of drug resistance mechanism.

Objective To analyze the pathogenic composition of hand, foot and mouth disease (HFMD) cases and the antibody level of enterovirus 71 (EV-A71) in healthy people in Xi&#39;an in 2022, so as to provide evidence for the prevention and control of HFMD. Methods Anal swabs or stool specimens of HFMD cases were collected. RT-PCR was used to detect enterovirus (EV) and serotype was identified. Enzyme-linked immunosorbent assay (ELISA) was used to detect EV-A71 IgG antibody levels in healthy people. Results A total of 172 positive cases were detected from 274 HFMD clinical specimens with a total detection rate of 62.77%, including 1 case of EV-A71 (0.58%), 95 cases of CV-A16 (55.23%), 64 cases of CV-A6 (37.21%), and 1 case of CV-A10(0.58%). CV-A16 was the dominant pathogen in spring and summer, and CV-A6 was the dominant pathogen in autumn and winter（χ²= 64.376，P＜0.001）. The age of HFMD cases caused by CV-A16 was older than the cases caused by CV-A6（t = 2.709，P = 0.007）. The positive rate of EV-A71 IgG antibodies in healthy people was 36.92% (168/455). The positive rate of EV-A71 IgG antibodies in men (32.35%) was lower than that in women (43.72%), and the difference was statistically significant (χ²= 6.605 , P = 0.014). The positive rate of EV-A71 IgG antibodies in people of all ages ranged from 21.95% to 54.78%, and the difference was statistically significant (χ²= 27.623 , P<0.001). Conclusion The main pathogens of hand, foot and mouth disease in Xi&#39;an in 2022 are CV-A16 and CV-A6 . The positive rate of EV-A71 IgG antibodies in children under 5 years old is low , and EV-A71 vaccination should be strengthened.

Abstract OBJECTIVE To investigate the specific binding of nucleic acid aptamers(k-α2ct) with plasminogen Kringle 5(K5) on the function of K5 in inhibiting proliferation and migration of vascular endothelial cells and promoting their apoptosis. METHODS The cloning and expression of recombinant K5 protein were performed by using a prokaryotic system, and the isolation and purification of the expressed K5 protein were performed by affinity chromatography. The affinity and specificity of K-a2ct and K5 were verified using isothermal titration calorimetry(ITC) and enzyme-linked oligonucleotide adsorption assay(ELONA). The effect of K-a2ct on the function of K5 in inhibiting the proliferation and migration of human umbilical vein endothelial cells(HUVEC) was investigated by CCK-8 and cell scratch assay. The apoptotic morphology of HUVEC cells stained with Hoechst 33342 was observed by laser confocal microscopy, and the effect of K-a2ct on the apoptosis- promoting function of K5 in HUVEC cells was also examined by Annexin V/PI double-stained flow cytometry. RESULTS Recombinant protein K5 was efficiently expressed in Escherichia coli and purified by affinity chromatography, identified as having a relative molecular weight of 12 kDa and a concentration of 0.32 mg·mL-1. ITC and ELONA results demonstrated that K-a2ct had a strong affinity and good selectivity for K5, showing the affinity specificity of a typical nucleic acid aptamer. CCK-8 and cell scratching assays showed that K-a2ct could inhibit the anti-proliferation and anti-migration effects of K5 on HUVEC cells in a dose-dependent manner. The laser confocal and flow cytometry results showed that K-a2ct inhibited the apoptosis-promoting function of K5 on HUVEC cells, mainly affecting late apoptosis of HUVEC cells effected by K5 but having little effect on early apoptosis. CONCLUSION The nucleic acid aptamers K-a2ct binds to K5 with high affinity and specificity, and inhibits its anti angiogenic function in a dose-dependent manner. It has great potential in targeting the regulation of K5 concentration and function in vivo and promoting angiogenesis.

[摘 要] 目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和BCLAF1蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与BCLAF1在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。