OBJECTIVE To analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

[摘 要] 目的：构建负载STING激动剂DMXAA的锰卟啉金属有机框架纳米颗粒（DPM），探讨其对三阴性乳腺癌（TNBC）细胞4T1及其小鼠移植瘤的治疗效果。方法：通过物理吸附法制备 DPM 纳米颗粒，利用透射电镜、扫描电镜及纳米粒度电位仪表征其形貌与理化性质。常规培养4T1细胞，细胞实验分为对照组、超声辐照组（US组）、DPM治疗组（DPM组）和DPM治疗联合超声辐照组（DPM + US组），用CCK-8法检测细胞活性，免疫荧光法检测高迁移率族蛋白B1（HMGB1）和钙网蛋白（CRT）的表达，WB法检测STING通路相关蛋白的表达。构建4T1细胞移植瘤小鼠模型，分为四组，处理同细胞实验，测量肿瘤体积，免疫荧光法检测移植瘤组织中Ki-67、HMGB1、CRT和缺氧诱导因子-1ɑ（HIF-1ɑ）蛋白的表达，TUNEL法检测细胞凋亡，流式细胞术检测免疫细胞活化情况，对主要器官进行H-E染色，以评估纳米材料的体内安全性。结果：DPM呈梭形，平均粒径（268 ± 3.302）nm，电位（33.1 ± 0.87）mV。细胞实验中，DPM联合超声辐照可明显抑制4T1细胞的增殖（P < 0.001），提高4T1细胞中ROS水平（P < 0.001），诱导4T1细胞CRT表达上调（P < 0.001），HMGB1从细胞核中移至细胞质，激活STING信号通路[p-STING、p-TBK1、p-IRF3蛋白表达均显著增加（均P < 0.001）]。体内实验中，DPM联合超声辐照可显著抑制4T1细胞移植瘤生长（P < 0.001）并促进免疫细胞表型转化（P < 0.001），抑制移植瘤组织中Ki-67、HIF-1α蛋白表达（均P < 0.01），谷胱甘肽（GSH）产生（P < 0.01），促进CRT、HMGB1蛋白表达、ROS产生（P < 0.001），对主要器官结构无明显影响。结论： DPM联合超声辐照可通过激活STING通路显著抑制4T1细胞及其移植瘤的生长，诱导抗肿瘤免疫应答，且对主要器官无明显毒性。

ObjectiveTo explore the feasibility of constructing a programmed death receptor-1（PD-1） molecular probe for non-invasive micro-positron emission tomography/computed tomography （Micro-PET/CT） imaging of PD-1 protein in mouse S180 sarcoma. MethodsA transgenic PD-1 C57 S180 sarcoma mouse model was established using the S180 sarcoma cell injection. Furthermore， ¹²⁴I-anti-PD-1 monoclonal antibody probe was synthesized. 18.5 MBq of the ¹²⁴I-anti-PD-1 probe was injected into the tail vein of transgenic PD-1 C57 mice. Subsequently， S180 sarcoma was imaged using Micro-PET/CT. ResultsStudy successfully established a transgenic PD-1 C57 S180 sarcoma mouse model. Immunohistochemical （IHC） results showed PD-1 protein expression in S180 sarcoma. Micro-PET/CT imaging successfully visualized the PD-1 protein receptor in S180 sarcoma at different time points （20， 48， 72， and 120 h） after probe injection. ConclusionThe ¹²⁴I-anti-PD-1 monoclonal antibody molecular probe successfully targets the PD-1 receptor in S180 sarcoma of transgenic PD-1 C57 mice， and presents clear Micro-PET/CT immunoassay results， thus it potentially enables the non-invasive screening of patients with PD-1 positive malignant tumors.

Objective To provide a scientific basis for vector prevention and control in port areas, vector monitoring has been conducted continuously to characterize the composition, density, and seasonal fluctuations of vectors across 21 port-areas of Shandong province from 2017 to 2023. Methods In accordance with the Regional Vector Monitoring Plan for Frontier Ports, vector surveillance of mosquitoes, flies, cockroaches, rodents, and other disease vectors was performed. Data were analyzed to describe vector community composition and identify seasonal fluctuations. Results A total of 601 rodents belonging to 1 family, 4 genera, and 4 species were captured. Three dominant rodent species inhabit port areas. In addition, 88 104 mosquitoes were captured and classified into 3 subfamilies, 4 genera, and 12 species; 38 959 flies were trapped and classified into 8 families,31 genera, and 51 species, including 9 dominant fly species in port-areas; and 54 672 captured cockroaches were classified into 2 families,4 genera, and 4 species, with Blattella germanica as the dominant species. Conclusions Significant vector community changes(P＜0.005)have been identified after the epidemic. To improve the pertinence and efficacy of port health quarantine work, continuous and strong attention should be paid to vector compositions and population densities at Shandong ports.

Objective This study aimed to investigate the genetic diversity, differentiation, and population structure of Aedes albopictus across different geographical regions in Shandong Province, and to explore the relationship between genetic diversity and geographical distribution. Methods Between July and August 2024, ten Ae. albopictus populations were sampled from seven cities in Shandong Province. Genomic DNA was extracted from individual mosquitoes, and the mitochondrial cytochrome c oxidase subunit I(COⅠ)gene was amplified using PCR and sequenced. The obtained sequences were verified using BLAST and analyzed with MAFFT, MEGA 11, DnaSP v6.12, Arlequin 3.5, PopART 1.7, STRUCTURE 2.3.4 and the R packages adegenet and vegan to assess genetic diversity and population structure. Results A total of 229 COⅠ sequences(662 bp) was obtained, revealing ten variable sites with no insertions or deletions. The overall base composition showed an AT bias of 67.7%. Haplotype analysis identified 11 haplotypes, with Hap2 being the dominant and most widely distributed haplotype across all populations. Neutrality tests showed significant population expansion only in the Rizhao population. Mantel testing result revealed that geographical distance does not significantly impede gene flow. Overall, genetic differentiation among populations was low, indicating frequent gene flow. When combined with additional samples from Shanghai, Fujian, Guangdong, Yunnan, Hainan and Guangxi, STRUCTURE, UPGMA and DAPC analyses revealed two primary genetic clusters of Ae. albopictus. Conclusions Ae. albopictus populations in Shandong Province exhibit frequent gene flow, low genetic differentiation, and relatively low overall genetic diversity. However, the Rizhao population showed signs of recent expansion, highlighting the need for enhanced surveillance and targeted control measures in this area.

OBJECTIVE To analyze the situation of urinary tract infections(UTIs)in children of different age groups in a health care hospital of Guangxi,and to analyze the detected pathogens and drug resistance rate.METHOD Data on urinary tract infections in children between 2017 and 2023 in Guangxi provincial maternal and child healthcare hospitals were retrospectively analyzed,and children were classified according to age:neonates(≤28 days),infants(＞28 days and ≤1 year),preschoolers(＞1 year and＜6 year)and 6-14 years old.The urina-ry tract infections,pathogen identification and drug resistance rates of major pathogens in children of different age groups were analyzed.RESULTS The pathogens of pediatric UTIs in each group were dominated by gram-negative bacilli(44.16％-67.36％),with the highest percentage of Escherichia coli(21.81％—38.60％),gram-posi-tive infections were dominated by Enterococcus faecium(5.96％—21.40％)and Enterococcus faecalis(4.66％—13.68％),and fungi were dominated by Candida albicans(8.03％-12.75％).Admission to intensive care unit was higher in the neonates group(37.38％,P＜0.001).Urine culture positivity rate was elevated in the 6-14 years age group(31.93％,P＜0.001),with girls being more common(59.47％,P＜0.001).The rate of E.coli resistance to cephalosporins was relative high in urine culture isolates from the infant group(28％—54％).In ad-dition,the resistance rate of Enterococcus faecium from urine to ampicillin was higher in the infant group than that in the preschool children and 6-14 years old groups(P=0.002).CONCLUSIONS The gram-negative bacteri-a were dominant among the pathogens isolated from the children with urinary tract infections and showed certain drug resistance to the commonly used antibiotics.Urinary tract infections are more difficult to diagnose and treat in younger children,and pediatricians should pay more attention to them.

Objective:To investigate the function and mechanism of exosome Linc00665 in modulating CD8+T cell immunoreactivity to promote radiotherapy resistance in OSCC.Methods:HOEC,SCC9 and SCC9-RR exosomes were extracted and identified,and the expression of Linc00665 was detected by qRT-PCR in cell lines and exosomes.The expression of TNF-α,IFN-γ,perforin and granzyme B in each treatment group was detected by ELISA(PBS,SCC9 exo,SCC9-RR exo).The killing ability of CD8+T cells against SCC9 cells in each treatment group was detected by CCK-8 assay.The targets of Linc00665 were further bioinformatically ana-lyzed and verified by qRT-PCR and Western blot.The expression of Linc00665,miR-28-5p and PD-1 in CD8+T cells was exogenous-ly regulated,the expression of immunoreactive factors in the supernatants of each treatment group was detected by ELISA(NC,sh-Linc00665,miR-28-5p inhibitor,sh-PD-1),and the killing ability of cells in each group was detected by CCK-8 method.Results:The concentrations of TNF-α,IFN-γ,perforin and granzyme B in the supernatants of cell culture in the SCC9-RR exo/CD8+T group were significantly decreased compared with those in the PBS/CD8+T group and the SCC9 exo/CD8+T group(P＜0.05),and the kill-ing ability of the cells in the SCC9-RR exo group was significantly decreased compared with those in the PBS group and the SCC9 exo group(P＜0.05),suggesting that SCC9-RR exo could inhibit the tumor killing ability of CD8+T cells.qRT-PCR results suggested that Linc00665 was highly expressed in the SCC9-RR cell line as well as exosome(P＜0.05).It was further verified by bioinformat-ics analysis that Linc00665 could regulate PD-1 expression via miR-28-5p,thereby modulating CD8+T cell immunoreactivity to pro-mote OSCC radiotherapy resistance.Conclusion:Exosome Linc00665 regulates CD8+T cell immunoreactivity through miR-28-5p/PD-1 axis to promote OSCC radiotherapy resistance.

This paper reviews the current situation of massive open online course (MOOC) construction both domestically and internationally, highlighting the similarities, differences, and limitations of MOOC construction across nations. Based on the full-cycle MOOC construction of the "clinical epidemiology" course at Southern Medical University, including course design, resource integration, online deployment, and teaching evaluation, this study explored the significance, implementation path, and challenges of MOOC construction. This paper also reflects on the activation of teaching content, teacher-student interaction, and teaching mode, aiming to provide a reference for the construction and continuous enhancement of MOOC in China.

BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.

BACKGROUND:Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.OBJECTIVE:To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.METHODS:Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis,and special attention was paid to the core Chinese medicine constituents of these prescriptions.The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.RESULTS AND CONCLUSION:(1)We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1,2024.Among these,48 patent groups utilized marine traditional Chinese medicine.These prescriptions contained 183 Chinese herbal medicines,of which 13 marine traditional Chinese medicines were used 574 times in total,and the number of flavors used in a single patented formula ranged from 2 to 41.(2)Oyster was the most frequently used marine ingredient,while Dipsacus asper,epimedium,Rehmannia glutinosa,Eucommia ulmoides Oliv.were the most frequent non-marine components.Association rule analysis identified oyster,Dipsacus asper,and epimedium as the core drug group.Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB,AKT1,TP53,PPARG,and SRC.Sitosterol,liquiritigenin,japonine,luteolin,and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions.(3)The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis.(4)The molecular docking verified the beneficial interactions between core components and core targets.(5)The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin,sitosterol,kaempferol,and other components,aligning with the drug components identified by network pharmacology.Quantitative analysis indicated that flavonoids,terpenes,and alkaloids constituted a significant proportion of the compound medicine's components.