BACKGROUND:The study aims to investigate the potential of aptamers as diagnostic and targeted therapeutic tools for gastric cancer (GC) and other cancer types through the cell-systematic evolution of ligands by exponential enrichment (cell-SELEX) process. GC is associated with high global incidence rates and a substantial lack of effective targeted therapies. Aptamers have emerged as a promising innovation for both the diagnosis and targeted treatment of various cancers. METHODS:Cell-SELEX process was employed to screen for aptamers specific to GC cells, utilizing the GC cell lines HGC-27, MKN-45, SNU-638, and NUGC-3 as target cells. Aptamer affinity, specificity, and biological properties were evaluated through flow cytometry, and mass spectrometry was utilized to identify potential target proteins. RESULTS:Aptamer-gastric cancer (APT-GC) is efficiently internalized by GC cell lines (HGC-27, MKN-45, SNU-638, NUGC-3) through receptor-mediated endocytosis at concentrations up to 300 nM, with intracellular stability for at least 2 hours and stability in serum for up to 6 hours. Furthermore, APT-GC is internalized by various cancer cell types, suggesting its potential for broad application in pan-cancer diagnosis and treatment. CONCLUSION:APT-GC exhibits high affinity for GC cells and can also be internalized by diverse cancer cell types, positioning it as a versatile diagnostic and therapeutic agent for a wide range of cancers.

Colorectal cancer (CRC) is a prevalent and highly malignant tumor with a limited response to immune checkpoint inhibitor-based immunotherapy. There is an urgent need for novel immunomodulatory agents to enhance the immunotherapeutic response in CRC. Hedyotis diffusa, known for its immunomodulatory properties, has long been utilized as an adjunct in cancer treatment, positioning it as a potential source for discovering new tumor immunomodulators. In this study, we identified a polysaccharide derived from Hedyotis diffusa (HDP), comprising six monosaccharides: rhamnose, arabinose, galactose, glucose, xylose, and mannose. When combined with PD-1 and CTLA-4 inhibitors, HDP can boost systemic immunity in mice to enhance the effectiveness of immune checkpoint inhibitors in CRC therapy. HDP significantly increases the infiltration of CD4+ and CD8+ T cells into tumor microenvironment and upregulates the expression of key effector molecules derived from cytotoxic T cells. Mechanistic studies reveal that HDP activates the IL-2/IL-2R axis by upregulating IL-2 production and the expression of IL-2 receptor subunits, thereby promoting T cell proliferation. Collectively, this research introduces an innovative strategy to improve the efficacy of tumor immunotherapy by harnessing the immunomodulatory potential of polysaccharides. It also directs a roadmap for developing HDP as a promising immunomodulator for CRC treatment.

Introduction: Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and A. dahurica alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated.Methods: HeLa and SiHa cell lines were utilized for in vitro experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the in vivo experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups.Results: In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased (p < 0.001), while the G2/M phase increased notably (p < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines (p < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated (p < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased (p < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues.Discussion: GEB exhibits a robust antitumor effect against cervical cancer, both in vitro and in vivo, in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.

It has been claimed that Dendrobium officinale polysaccharides (PSs) can degrade into oligosaccharide and then transform into short-chain fatty acids in the intestine after oral administration, and play an anti-colitis-associated cancer (CAC) effect by inhibiting intestinal inflammation. However, the material basis and core chemical structure underlying the anti-colon cancer properties of PSs have not yet been elucidated. In this study, PSs were degraded into enzymatic oligosaccharides (OSs) using β-mannanase. The results of in vivo experiments revealed that PSs and OSs administered by gastric lavage had similar antitumor effects in CAC mice. OS-1 (Oligosaccharide compounds 1) and OS-2 (Oligosaccharide compounds 2) were further purified and characterized from OSs, and it was found that OS-1, OS-2, OSs, and PSs had similar and consistent anti-inflammatory activities in vitro. Chemical structure comparison and evaluation revealed that the chemical structure of β-D-Manp-(1 → 4)-β-D-Glcp corresponding to OS-1 was the least common PS structure with anti-colitic activity. Therefore, our findings suggest that OSs are the material basis for PSs to exert anti-CAC activity and that the chemical structure of β-D-Manp-(1 → 4)-β-D-Glcp corresponding to OS-1 is the core chemical structure of PSs against CAC.

目的 观察云南白药促进骨折愈合的作用及其机制.方法 将新西兰兔分为云南白药组、模型对照组与正常对照组,每组6只.云南白药组与模型对照组建立左前肢桡骨骨折模型.云南白药组将载云南白药无菌纱布用夹板外固定在造模部位对侧面,5 g·kg-1,每3 d换药1次;模型对照组与正常对照组不敷药,其他处理同云南白药组.X线观察骨折愈合进展,检测血清钙磷,酶联免疫吸附(ELISA)检测血清白细胞介素6(IL-6)、肿瘤坏死引子α(TNF-α)、骨钙素(OC)、Ⅰ型前胶原N端肽(PINP)、碱性成纤维细胞生长因子(bFGF)、碱性磷酸酶(ALP)及酸性磷酸酶5(ACP5)浓度,苏木精-伊红(HE)染色检测骨折愈合进程,免疫组织化学(IHC)检测骨折部位骨母细胞bFGF表达.结果 与正常对照组比较,模型对照组血清钙、磷、IL-6、TNF-α、OC、PINP、bFGF、ALP等浓度升高(P<0.05);与模型对照组比较,云南白药组骨折线提前1周消失,血清钙峰值提前1周出现,钙磷乘积峰值显著升高(P<0.05),IL-6、TNF-α下降速度更快、浓度更低(P<0.05),血清OC、PINP、bFGF、ALP浓度更高(P<0.05),血清ACP5浓度在造模后第1周达到峰值,随后呈快速下降趋势,骨骨痂、骨髓腔形成与贯通、骨钙化和血管生成时间显著提前,骨母细胞bFGF表达量更高(P<0.05).结论

We investigated the antitumor effects of four fractions of Dendrobium officinale Kimura & Migo (D. officinale) polysaccharides with different molecular weights (Mw), Astragalus membranaceus polysaccharides (APS) and Lentinus edodes polysaccharides (LNT) on colorectal cancer (CRC) using a zebrafish xenograft model. Transcriptome sequencing was performed to further explore the possible antitumor mechanisms of D. officinale polysaccharides. Fractions of D. officinale polysaccharides, LNT, and APS could significantly inhibit the growth of HT-29 cells in a zebrafish xenograft model. One fraction of D. officinale polysaccharides called DOPW-1 (Mw of 389.98 kDa) exhibited the strongest tumor inhibition. Compared with the control group, RNA-seq revealed that the DOPW-1–treated experimental group had 119 differentially expressed genes (DEGs), of which 45 had upregulated expression and 74 had downregulated expression. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes suggested that the pathway “apoptosis-multiple species” was the most significantly enriched. Our data indicated that 1) fractions of D. officinale polysaccharides of Mw 389.98 kDa were most suitable against CRC; 2) DOPW-1 could be developed into a clinical agent against CRC; and 3) an apoptosis pathway is important for DOPW-1 to inhibit the proliferation of HT-29 cells.

目的:研究白花鬼针草醇提物的化学成分.方法:以硅胶色谱、Sephadex LH-20色谱及C18反相硅色谱分离纯化白花鬼针草醇提物的化学成分,以1 H-NMR、13C-NMR以及质谱鉴定化学结构.结果:从白花鬼针草醇提物中分离、纯化、鉴定了6个化合物,分别为:槲皮素-3,3'-二甲醚-7-O-β-D-吡喃酮葡萄糖苷(1)、奥卡宁4'-O-β-D-(2″,4″,6″-三乙酰基)-吡喃酮葡萄糖苷(2)、4-O-(6″-O-对-香豆酰基-β-D-吡喃酮葡萄糖)-对-香豆酸(3)、4-O-(2″-O-乙酰基-6″-O-对-香豆酰基-β-D-吡喃酮葡萄糖)-对-香豆酸(4)、邻苯二甲酸异丙酯(5)、原儿茶酸(6).结论:6个化合物均首次从白花鬼针草中分离得到,其中,槲皮素-3,3'-二甲醚-7-O-β-D-吡喃酮葡萄糖苷(1)、4-O-(6″-O-对-香豆酰基-β-D-吡喃酮葡萄糖)-对-香豆酸(3)、4-O-(2″-O-乙酰基-6″-O-对-香豆酰基-β-D-吡喃酮葡萄糖)-对-香豆酸(4)、邻苯二甲酸异丙酯(5)4个化合物属于首次从鬼针草数药用植物植物中分离鉴定.

1 临床资料 患者,男,60岁,因"腰椎术后髋关节疼痛,下肢乏力,发热3天"于2017年1月3日入院.既往有高血压病史10余年.否认冠心病、肝炎、肺结核病史,否认外伤、输血史,否认药物及食物过敏史,有吸烟史30年,每日20支,已戒烟7个月,偶有少许饮酒.2016年5月11日于某医院行"髂骨取骨,腰椎病变清除病灶,植骨融合钉内固定术",术后间断感髋关节疼痛.近1个月感双下肢乏力,行走无力,未行特殊检查及治疗.

本文报道1例白血病化疗中大剂量甲氨蝶呤排泄延迟患儿的个体化治疗实践,探讨在儿童白血病化疗中大剂量甲氨蝶呤排泄延迟解救的个体化治疗.临床药师利用药物基因检测预警甲氨蝶呤排泄延迟及不良反应风险,并提前做好相应预防措施,通过血药浓度监测指导亚叶酸钙解救,针对导致甲氨蝶呤排泄的危险因素(药物相互作用、尿液pH、尿液量、呕吐等)采取应对措施,为甲氨蝶呤排泄延迟患儿实施个体化解救,在保持化疗效果同时避免甲氨蝶呤毒性蓄积,可为同类患儿的甲氨蝶呤个体化治疗提供借鉴.

目的:研究大叶井口边草乙酸乙酯部位的化学成分.方法:采用硅胶柱色谱、Sephadex LH-20柱色谱、RP-C18柱色谱和半制备高效液相色谱法对大叶井口边草乙酸乙酯部位的化学成分进行分离纯化,通过理化性质、1 H-NMR、13C-NMR和MS等方法鉴定化合物结构.结果:从大叶井口边草乙酸乙酯部位中分离纯化了 17个化合物,分别鉴定为:ent-3β-hydroxy-kaur-16-ene(1)、ent-2β,15α-dihydroxy-kaur-16-ene(2)、ent-3β,19-dihydroxy-kaur-16-ene(3)、ent-2β,6β,15α-trihydroxy-kaur-16-ene(4)、蕨素 B(5)、芹菜素(6)、木犀草素(7)、槲皮素(8)、6-甲氧基槲皮素(9)、6-甲氧基柚皮素(10)、槲皮素-3-O-β-D-吡喃葡萄糖苷(11)、木犀草苷(12)、芹菜素-7-O-β-D-葡萄糖苷(13)、芹菜素-7-O-β-D-葡萄糖醛酸苷甲酯(14)、咖啡酸(15)、咖啡酸甲酯(16)、β-谷甾醇(17).结论:其中,化合物1、3、7～16为首次从该植物中分离得到.

目的:研究闽产白花鬼针草乙酸乙酯部位化学成分.方法:以硅胶色谱、SephadexLH-20色谱及C18反相硅胶色谱分离纯化乙酸乙酯部位的化学成分,以1 H-NMR、13C-NMR以及质谱鉴定化学结构.结果:从白花鬼针草乙酸乙酯部位分离、纯化、鉴定了6个黄酮类化合物,分别为:3,3'-二甲氧基槲皮素(1)、2'-羟基-4,4'-二甲氧基查耳酮(2)、山奈酚(3)、槲皮素-3-甲氧基-7-O-β-D-吡喃葡萄糖苷(4)、槲皮素-3,3'-二甲氧基-7-O-β-D-吡喃葡萄糖苷(5)、奥卡宁4'-O-β-D-(2″,4″,6″-三乙酰基)-吡喃葡萄糖苷(6).结论:6个化合物均首次从白花鬼针草中分离得到,其中,3,3'-二甲氧基槲皮素(1)、槲皮素-3-甲氧基-7-O-β-D-吡喃葡萄糖苷(4)、槲皮素-3,3'-二甲氧基-7-O-β-D-吡喃葡萄糖苷(5)3个化合物属于首次从鬼针草属药用植物中分离鉴定.

辅助用药价格虚高和滥用是公立医院普遍面临的问题.《关于加强三级公立医院绩效考核工作的意见》明确将三级公立医院的辅助用药收入占比纳入医务人员绩效考核指标,促使医院重视辅助用药合理应用与管控.从组织构架及职责、工作程序、管理制度、软件建设等方面阐述了恩施土家族苗族自治州中心医院临床合理用药管理机制,从事前、事中、事后3个角度介绍了该院以辅助用药管控为重点的临床合理用药实践,分析了其辅助用药管理特色,为公立医院辅助用药管理提供参考.

目的:对超富硒药材恩施堇叶碎米荠的基源、产地、富硒能力及其有机硒化合物成分与活性的研究进展进行综述.方法:检索恩施堇叶碎米荠所有文献,并把文献按基源研究、富硒概述及有机硒化合物研究进展进行分类.结果:恩施堇叶碎米荠(Candamine woliholia)来源于十字花科碎米荠属堇叶碎米荠的全草,主产于湖北、湖南、广西、广东等地,于2011年被证实有超富硒能力,目前从中分离并鉴定5个硒多糖及1个硒蛋白;关于有机硒化合物生物活性的研究目前涉及抗氧化、免疫调节及抗运动性疲劳3个方面.结论:恩施堇叶碎米荠的基源、产地及超富硒能力已被证实,但关于其有机硒的成分研究有待从提取、分离、纯化及结构鉴定等方面进行研究,其有机硒化合物的生物活性研究有待从单体化合物进行深入和拓宽.

Objective To investigate the different polar parts extracted from radix Vitis davidii Fo?x on fracture healing in SD rats. Methods A model of the radial fracture of the left forelimb was made in SD rats. The activity of different polar parts extracted from radix Vitis davidii Fo?x on fracture healing in fracture SD rats was research by the determination of the Calcium ions and Alkaline phosphatase concentration in serum,the HE staining of fracture tissue,and RT-PCR detection was used to detect VEGF mRNA expression of radius fracture organization. Results Compared with the blank group, the serum concentration of AKP was significantly increased by n-butanol extract and ethyl acetate extract of radix Vitis davidii Fo?x (P<0.05),the time of peak calcium concentration and the decrease of calcium concentration were advanced (P<0. 05). The peak time of calcium concentration and reduced time of calcium concentration the was improved(P<0.05),the occurrence time of cartilage cells and fibrous callus were in-creased,the growth rate of callus were increased, the shaping time of fracture site and the time of bone marrow cavity perforation were advanced, and the expression level of VEGF mRNA was increased (P<0.05). Conclusion Ethyl acetate extraction and n-butanol extraction from radix Vitis davidii Fo?x have a significant effect on the healing of radius fracture in SD rats.

目的:制备鬼二白凝胶,并进行安全性试验.方法:将处方药材经回流提取、浓缩、干燥、粉碎制成干粉,溶于乙醇后加入丙二醇,混入调制好的卡波姆,制成凝胶剂;分别对进行大鼠皮肤急性毒性、豚鼠皮肤刺激性、豚鼠皮肤过敏性及大鼠长期毒性试验,观察大鼠一般情况及体质量,并检测大鼠血液生化情况和心、脑、肝、肾变化情况.结果:皮肤急性毒性试验中,大鼠完整皮肤及破损皮肤均未出现红斑及水肿;豚鼠皮肤刺激性试验中,仅破损皮肤组出现轻度红斑及水肿,完整皮肤组未出现异常情况;豚鼠皮肤过敏性试验中,仅高剂量组产生轻微过敏反应,其他组豚鼠均正常;长期毒性试验中,仅高剂量组大鼠血液生化指标有一定影响,停药14 d后均恢复正常.结论:鬼二白凝胶临床剂量用于大鼠及豚鼠皮肤安全性良好.

Objective To investigate the effect of effective fractions from Radix Vitis Davidii Foex. on fracture healing. Methods SD rats were randomly divided into model control group,Yunnan Baiyao group,and effective fraction group (n= 36 each group). Fracture models were established. Rats in the Yunnan Baiyao group and effective fraction group were given 3.0 g?kg-1?d-1 of Yunnan Baiyao and effective fraction from Radix Vitis Davidii Foex.,respectively,and rats in the model control group was treated with the same volume of pure water. Alkaline phosphatase and Ca concentration in serum were determined.For radius fracture structure,digital radiography and RT-PCR detection of VEGF mRNA expression were performed. Results The peak concentration of the alkaline phosphatase and Ca concentration in serum were significantly higher in the effective fraction group than in the Yunnan Baiyao group,and peak value appeared earlier,fracture healing score was higher, fracture line disappeared earlier,and VEGF mRNA expression was significantly higher in three weeks after the fracture (all P<0. 01) . Conclusion The effect of the effective fraction from RadixVitis Davidii Foex.on the fracture healing is strong.

目的 观察白花鬼针草乙酸乙酯部位对RKO细胞线粒体膜电位的影响. 方法 用95％乙醇提取白花鬼针草,系统溶剂法按极性由低到高依次萃取,得到乙酸乙酯部位(EE-BP),通过流式细胞术方法,以JC-1为探针,检测不同浓度的EE-BP对RKO细胞线粒体膜电位变化的影响. 结果 EE-BP能显著降低RKO细胞的线粒体膜电位,具有明显的量效关系,随着给药浓度的增加,线粒体膜电位下降明显,差异具有统计学意义(P＜0.01). 结论 白花鬼针草乙酸乙酯部位能通过降低线粒体膜电位,诱导RKO细胞的凋亡,具有显著的抗肿瘤活性.

Objective: To investigate the mechanism on apoptosis of human colon cancer cell lines of RKO induced by Trillium tschonoskii Maxim. Methods: The human colon cancer cell lines RKO were used for the antitumor activity assay and the cytotoxicity of different extractions from Trillium tschonoskii Maxim were evaluated by using MTT method. Furthermore,the mitochondrial membrane potential and activity of Caspase9 and Caspase3 of RKO cells induced by EE-TM were detected by flow cytometry and photocolorimetry. Results: EE-TM exhibited the most remarkable anti-proliferative activity against RKO cells than other extracts( P 0. 01),and inhibited the proliferation of RKO cells significantly with the IC50value of 52. 64,22. 56,18. 39 μg /mL in 24,48,72 h,respectively. EE-TM has induced disintegration of mitochondrial membrane potential of RKO cells treated with for 12 h( P 0. 01),and made the activity of Caspase9 and Caspase3 enhance. Conclusions: The Trillium tschonoskii Maxim has anti-colon cancer activity in vitro and mitochondrial apoptotic pathway may be one of the mechanism of action.

目的:测定延龄草不同提取部位中总酚的含量。方法:以没食子酸为对照品,采用福林酚法测定延龄草不同提取部位总酚含量。结果:没食子酸在0.312 5～40mg.L-1范围内线性关系良好(r=0.999 3)。延龄草不同提取部位中总酚含量由高到低的排列顺序为:醋酸乙酯部位、正丁醇部位、乙醇提取部位、水提取部位、石油醚部位。结论:延龄草中总酚含量较高,主要分布在醋酸乙酯部位和正丁醇部位。