新生儿期的免疫系统发育阶段对维持新生儿健康至关重要,具有独特的免疫调节机制。近年来,人们越来越关注髓源性抑制细胞（MDSCs）在新生儿免疫调节中的作用。MDSCs是一类免疫抑制功能强大的异质性细胞群体,它们能够通过多种机制调节免疫应答。MDSCs在新生儿中的调节作用对防止过度免疫反应和促进免疫耐受至关重要,有助于预防新生儿期炎症性疾病,并对其后续健康产生积极影响。近期研究文献分析展示了MDSCs在新生儿免疫调节中的多种作用机制,包括在特定病理条件下的保护作用、与新生儿期炎症反应的相互作用,以及对长期免疫发展的潜在影响。因此,深入理解MDSCs在新生儿免疫中的角色,不仅有助于揭示其复杂的调节机制,也为制定新的预防和治疗新生儿炎症性疾病的策略提供了新的思路。

The developmental stage of the immune system during the neonatal period is crucial for maintaining neonatal health,characterized by unique immunoregulatory mechanisms．In recent years,increasing attention has been drawn to the role of myeloid-derived suppressor cells（MDSCs）in neonatal immune regulation．MDSCs represents a heterogeneous population of cells with potent immunosuppressive functions,capable of modulating immune responses through various mechanisms．The regulatory role of MDSCs in neonates is vital for preventing excessive immune reactions and promoting immune tolerance,thereby aiding in the prevention of neonatal inflammatory diseases and positively influencing subsequent health outcomes．Analysis of recent research literature reveals multiple mechanisms through which MDSCs contribute to neonatal immune regulation,including protective effects under specific pathological conditions,interactions with neonatal inflammatory responses,and potential impacts on long-term immune development．Therefore,a comprehensive understanding of the role of MDSCs in neonatal immunity not only helps elucidate their intricate regulatory mechanisms but also provides novel insights for developing strategies for the prevention and treatment of neonatal inflammatory diseases．

目的 探讨NXT629改善肝胆结石形成的相关机制。方法 对C57BL/6J小鼠分别采用常规饮食或成石饮食（LD）喂养,并在LD组小鼠注射PPAR-α拮抗剂NXT629。通过苏木精-伊红染色法染色分析肝脂肪病变,油红O染色检测肝脏脂质的积累,分光光度法检测胆汁或血清中总胆固醇、甘油三酯、磷脂、总胆汁酸、胆固醇饱和指数、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇指标;qPCR法检测小鼠肝组织中ABCG5/8、CYP7A1、CYP7B1、PPAR-α和ABCB11 mRNA的表达情况。结果 NXT629通过靶向PPAR-α降低LD组小鼠肝脏中的ABCG5、ABCG8、ABCB11 mRNA水平以及增加CYP7A1、CYP7B1 mRNA水平,进而减少LD诱导的肝胆结石形成并改善脂质代谢紊乱。结论 NXT629可能通过影响脂代谢相关基因表达改善肝胆结石。

Objective To explore the mechanism on NXT629 improves hepatolithiasis formation．Methods C57BL/6J mice were fed either a regular diet or a lithogenic diet（LD）,with the LD group receiving injections of PPAR-α inhibitor NXT629．Liver steatosis was analyzed via HE staining,hepatic lipid accumulation was detected by Oil Red O staining,and total cholesterol,triglycerides,phospholipids,total bile acids,cholesterol saturation index,low density lipoprotein cholesterol,and high density lipoprotein cholesterol levels in bile or serum were measured using assay kits．RT-qPCR was employed to determine the mRNA expression of ABCG5/8,CYP7A1,CYP7B1,PPAR-α,and ABCB11 in mouse liver tissues．Results The Results showed that NXT629 target PPAR-α to down-regulate the mRNA levels of ABCG5,ABCG8,and ABCB11 in the livers of LD-fed mice,while increasing the mRNA levels of CYP7A1 and CYP7B1,thereby reducing LD-induced hepatolithiasis formation and improving lipid metabolism disorders．Conclusions NXT629 can improve cholesterol gallstones by affecting the expression of genes related to lipid metabolism．

腹腔镜手术后除躯体创伤疼痛,部分患者还可能经历痛苦的术后内脏痛,不仅使患者术后体验不佳,疼痛应激甚至可能加重机体的内环境紊乱,不利于患者的术后康复。内脏痛是来源于内脏器官和组织的疼痛,其产生与脏器的平滑肌痉挛、扩张、缺血、化学炎症刺激等密切相关。在这个过程中,许多离子通道和受体在调节内脏伤害性刺激信号的传导上发挥作用。目前,临床上术后镇痛治疗方案多样,但如何针对性地控制术后内脏痛是临床医生需要面对和解决的问题。为此,该文对腹腔镜术后内脏痛发生的相关机制、内脏感觉的神经传导及临床特征、治疗进展进行综述。

In addition to physical trauma,patients undergoing laparoscopic surgery may also experience postoperative visceral pain．This pain not only impacts the patient's postoperative experience,but can also worsen the body's internal environment and hinder recovery．Visceral pain originates from internal organs and tissues．It is closely related to smooth muscle spasms,dilations,ischemia,and chemical inflammatory stimulation of organs．In this process,numerous ion channels and receptors regulate the transmission of visceral nociceptive stimulus signals．At present,there are multiple clinical treatment options available for postoperative pain management．However,clinicians must overcome the challenge of controlling postoperative visceral pain．This article provides a review of the relevant mechanisms of visceral pain following laparoscopic surgery,the neural conduction of visceral sensation,clinical characteristics and treatment advancements．

纳米材料作为一种新兴材料,在疾病诊断与治疗中拥有极大的应用潜力。为平衡纳米材料的生物活性和生物毒性之间的关系,清楚了解纳米材料在体内的清除机制和清除速率至关重要。其中,肾脏,作为人体重要的清除器官,直接影响纳米材料从血液清除到尿液的速率,进而影响其在生物体内的血液循环、肿瘤靶向效率和体内滞留等系列问题,最终影响其临床应用。基于近年来已报道的关于纳米材料与肾脏相互作用的诸多研究,本文系统介绍了肾脏结构、纳米材料在肾脏中的传输机制、理化性质对其肾脏清除效率的影响以及纳米材料在肾脏疾病诊疗中的应用。本文有望为精准纳米医学的发展以及纳米材料未来的临床转化起到促进作用。

Nanomaterials, as emerging materials, show great promise for the detection, diagnosis and treatment of diseases. Fully understanding their elimination pathway and clearance efficiency is important to better balance the bioactivity and biotoxicity of nanomaterials. Kidneys, as a major organ, play a key role in the clearance of nanomaterials from blood to urine. The clearance rate of nanomaterials in the kidneys directly affects their blood circulation, retention in the body and tumor targeting efficiency as well as final clinical applications. Based on current understanding of nano-bio interactions of nanomaterials in the kidneys, in this review, we introduced the kidney structure and elimination mechanism of nanomaterials in the kidneys. Then, how the physicochemical properties of nanomaterials affect their renal clearance efficiency are summarized. Finally, their applications in the kidney disease detection and treatment are presented. The basic understanding of nano-bio interactions of nanomaterials in the kidneys would promote the development of precise nanomedicine and their future clinical translation.

目的 丹酚酸B是传统中药丹参的重要生物活性组分,临床应用广泛。新近发现,丹酚酸B具有防治骨质疏松的作用。本研究拟在前期工作基础上,系统地研究丹酚酸B对去卵巢骨质疏松小鼠的作用,探讨其对小鼠间充质干细胞（MSCs）成骨分化的影响。方法 将18只8周龄SPF级别的C57雌性小鼠分为假手术组、骨质疏松组、丹酚酸B治疗组。骨质疏松组和丹酚酸B治疗组行双侧卵巢摘除术。而假手术组则保持正常的卵巢结构,同时去除局部的脂肪。3组均于术后3日内给予抗生素进行抗感染治疗。4周内,丹酚酸B治疗组给予丹酚酸B 2.5 mg/kg腹腔注射,连续12周,2天1次,其余2组在相同的时间内给予等量生理盐水。16周后,在麻醉状态下将所有小鼠处死。应用MicroCT测量了小鼠右后股骨的骨密度。采用qRT-PCR技术,分析小鼠左后股骨骨髓MSCs中Runx2和Osterix的表达。将小鼠右后股骨进行液氮研磨处理,提取蛋白质,用WB法测定OPG和RANKL的含量。结果 骨质疏松组小鼠股骨骨密度比假手术组低（P<0.05）,丹酚酸B治疗组小鼠股骨骨密度比骨质疏松组高,但差异无显著性意义（P<0.05）。骨质疏松组小鼠Runx2和Osterix水平低于假手术组（P<0.05）,丹酚酸B治疗组小鼠Runx2和Osterix水平比骨质疏松组高（P<0.05）。骨质疏松组小鼠OPG和RANKL蛋白水平低于假手术组（P<0.05）,丹酚酸B组小鼠OPG和RANKL蛋白水平比骨质疏松组高（P<0.05）。结论 绝经后骨质疏松症早期对小鼠的骨质疏松具有一定的影响,但还需要更多的实验来验证本研究的结论。

Objective Salvianolic acid B is an important bioactive component of traditional Chinese medicine Salvia miltiorrhiza and is widely used in clinic．Recently,salvianolic acid B has been found to have the effect of preventing osteoporosis．On the basis of previous work,this study intends to systematically explore the effect of salvianolic acid B on ovariectomized mice with osteoporosis,and its effect on the osteogenic differentiation of mouse mesenchymal stem cells（MSCs）．Methods Eighteen eight-week-old SPF C57 female mice were divided into sham operation group,osteoporosis group and salvianolic acid B treatment group（6 mice in each group）．The osteoporosis group and salvianolic acid B group underwent bilateral ovariectomy．The sham group maintained normal ovarian structure while removing local fat tissue．All three groups were given antibiotics for anti-infection treatment within 3 days after operation．Within 4 weeks,salvianolic acid B treatment group was given salvianolic acid B 2.5 mg/kg intraperitoneal injection for 12 weeks,once every 2 days,and the other 2 groups were given the same amount of saline at the same time．After 16 weeks,all mice were sacrificed under anesthesia．The bone density of the mouse right posterior femur was measured by MicroCT．The expressions of Runx2 and Osterix in the bone marrow of mouse left posterior femur were analyzed by qRT-PCR．The right posterior femur of mice was ground with liquid nitrogen to extract protein,and the contents of OPG and RANKL were determined by WB．Results The bone mineral density of the femur in the osteoporosis group was lower than that in the sham operation group（P<0.05）,and the bone mineral density of the femur in the salvianolic acid B treatment group was higher than that in the osteoporosis group,but the difference was not significant（P<0.05）．The levels of Runx2 and Osterix in the osteoporosis group were significantly lower than those in the sham operation group（P<0.05）,and the levels of Runx2 and Osterix in the salvianolic acid B treatment group were higher than those in the osteoporosis group（P<0.05）．The levels of OPG and RANKL protein in the osteoporosis group were significantly lower than those in the sham operation group（P<0.05）,while the levels of OPG and RANKL protein in the salvianolic acid B group were higher than those in the osteoporosis group（P<0.05）．Conclusions The early stage of postmenopausal osteoporosis has certain effects on osteoporosis in mice,but more experiments are needed to verify the conclusions of this study．

目的 探讨柚皮素对人乳腺癌细胞株MCF-7和小鼠乳腺癌细胞系4T1的作用机制。方法 选择人乳腺癌细胞株MCF-7和小鼠乳腺癌细胞系4T1为实验对象,设置对照组和柚皮素组,其中柚皮素组分为20、40、80 和120 μmol/L 4个浓度,利用CCK-8、平板克隆形成实验检测柚皮素对乳腺癌细胞的增殖作用,应用流式细胞术检测柚皮素对乳腺癌细胞的凋亡作用。建立乳腺癌移植瘤模型,应用柚皮素作用于模型小鼠,探讨柚皮素在体内抗肿瘤作用。通过荧光定量PCR和蛋白免疫印迹实验检测自噬相关基因,分析其作用机制。结果 经柚皮素处理后,乳腺癌细胞的增殖明显受到抑制,正常乳腺癌细胞增殖情况变化不大,MCF-7乳腺癌细胞和小鼠乳腺癌4T1均出现明显的凋亡（P<0.001）。结论 柚皮素可以抑制乳腺癌细胞的增殖,且对正常乳腺细胞无明显毒副作用。柚皮素通过凋亡和自噬方式促进乳腺癌细胞的死亡,体内实验结果显示柚皮素具有抗肿瘤作用,并可促进其坏死。

实体肿瘤物理和化学微环境异常阻碍了肿瘤与外界进行物质交换,降低了药物渗入肿瘤组织,是肿瘤对放化疗抵抗的重要原因。目前,已有多种针对肿瘤微环境各个组分的治疗方法,如使血管正常化、降低肿瘤间质液压、降解细胞外基质等,以达到增强药物等的渗出,从而增强肿瘤治疗效果。声学调控是改变肿瘤理化微环境的一种有效方法,本文对声学调控其中几个主要的机制和研究进展进行综述,以期为临床肿瘤治疗提供新思路。

目的 通过生物信息学方法,分析阿司匹林抗结直肠癌的作用机制。方法 在DrugBank 5.1.5中查找阿司匹林的直接作用蛋白靶点(direct protein targets,DPTs);构建阿司匹林DPTs的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络并分析相关信号通路;从GEO数据库中获取结直肠癌表达谱芯片数据,筛选中心度最高的20个结直肠癌差异表达基因作为Hub基因;将DPTs相互关联基因与结直肠癌Hub基因求交集,确认阿司匹林抗结直肠癌的潜在作用靶点,分析其在TCGA数据库结肠腺癌样本中的表达情况,并进行GO功能富集分析和KEGG信号通路分析。最终通过RT-PCR和WB实验验证阿司匹林抗结直肠癌的潜在靶点。结果 在DrugBank 5.1.5中确定了11个阿司匹林DPTs,KEGG信号通路分析发现其中6个DPTs(EDNRA,IKBKB,NFKB2,NFKBIA,PTGS2,TP53)与癌症的发生发展有关。将DPTs相关联基因与筛选的20个结直肠癌Hub基因求交集,发现5个基因(CDK1,AURKA,CCNB1,MAD2L1,TPX2)可能是阿司匹林抗结直肠癌的潜在作用靶点,其在TCGA数据库结肠腺癌样本中均表达上调,基因功能主要富集于细胞周期调控。RT-PCR和WB实验结果显示阿司匹林可以降低人结肠癌细胞中CDK1,AURKA,CCNB1,MAD2L1,TPX2的mRNA水平和蛋白表达。结论 CDK1,AURKA,CCNB1,MAD2L1,TPX2可能是阿司匹林抗结直肠癌的潜在靶点,其可能通过影响细胞周期调控发挥抗肿瘤作用。

Objective To analyze the mechanism of aspirin against colorectal cancer(CRC)by bioinformatic analysis. Methods DrugBank 5.1.5 was used to identify direct protein targets (DPTs) of aspirin. The protein-protein interaction (PPI) network of DPTs was constructed and involved signaling pathways were analyzed. CRC-associated gene expression datasets were downloaded from GEO database, and the top twenty differentially expressed genes with the highest degree were screened out as Hub genes. Common genes between the genes associated with the DPTs and the Hub genes of CRC were the potential targets of aspirin against CRC. The potential targets in TCGA database colon adenocarcinoma (COAD) samples were examined. GO functional enrichment analysis and KEGG signaling pathway analysis of the potential targets were performed. The potential targets of aspirin against CRC cells were verified by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Results Eleven DPTs of aspirin were identified in DrugBank 5.1.5. KEGG signaling pathway showed that 6 genes (EDNRA, IKBKB, NFKB2, NFKBIA, PTGS2, TP53) were associated with the occurrence and development of CRC. By intersecting 20 Hub genes of CRC with genes associated with the DPTs of aspirin, it was found that 5 genes (CDK1, AURKA, CCNB1, MAD2L1, TPX2) might be the potential targets of aspirin against CRC. They were all up-regulated in TCGA-COAD samples, and the gene functions were mainly enriched in cell cycle regulation. The results of RT-PCR and WB showed that aspirin could down-regulate the mRNA and protein expression levels of CDK1, AURKA, CCNB1, MAD2L1 and TPX2 in human colon cancer cells respectively. Conclusion CDK1, AURKA, CCNB1, MAD2L1 and TPX2 could be potential targets of aspirin against CRC by affecting the progress of cell cycle regulation.

目的 基于网络药理学方法预测银杏叶治疗心肌缺血的潜在靶点及信号通路。方法 利用 TCMSP 平台筛选生物利用度(OB)≥ 30% 和类药性(DL)≥ 0.18 的活性成分及作用靶点。利用GeneCards和OMIM数据库检索心肌缺血疾病相关靶点,并提取药物成分和心肌缺血疾病的共有靶点作为关键靶点。通过在线TRING平台构建PPI网络,并采用Cytoscape 软件构建可视化的“化合物-靶点-通路”网络,进一步进行GO 功能富集分析和KEGG通路富集分析。结果 筛选得到 27种潜在的药效成分,2 164个化合物靶点,531个心肌缺血相关靶基因。两者取交集后获得疾病-类药活性成分40个共同靶点,PPI 蛋白互作网络自由度较高的节点依次为:IL6、VEGFA、CASP3、MAPK8、MYC、NOS3。GO 功能富集分析得到42个 GO 条目,KEGG 通路富集分析得到42条信号通路。结论 银杏叶治疗心肌缺血主要GO 能力富集在半胱氨酸肽链内切酶活性,内肽酶活力,激活转录因子结合,DNA结合转录激活剂活性,RNA聚合酶II特异性等功能,调控TNF信号通路,糖尿病并发症的年龄愤怒信号, 细胞凋亡,PI3K-Akt信号通路等信号,进一步达到对心肌缺血疾病的治疗。

Objective To predict the potential targets and signal pathways of ginkgo leaf in the treatment of myocardial ischemia based on network pharmacology. Methods The active components and targets of bioavailability (OB) ≥ 30% and drug-like (DL) ≥ 0.18 were screened by TCMSP platform.The related targets of myocardial ischemic diseases were searched by GeneCards and OMIM database, the components and the common targets of myocardial ischemic diseases were extracted as the key targets. To build the PPI network through the online STRING platform, a visual “compound-target-pathway” network was constructed to further analyze the functional enrichment of GO and the enrichment of KEGG pathway. Results 27 potential active components, 2 164 compound targets and 531 myocardial ischemia related target genes were screened. After the intersection of the two, 40 common targets of disease-class active components were obtained. The nodes with higher degree of freedom of PPI protein interaction network were IL6、VEGFA、CASP3、MAPK8、MYC and NOS3.42 entries were obtained by GO functional enrichment analysis and 42 signal pathways were obtained by KEGG pathway enrichment analysis. Conclusion Ginkgo leaf may be a target of cysteine-type endopeptidase activity,endopeptidase activity,activating transcription factor binding,DNA-binding transcription activator activity, RNA polymerase II-specific function. TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, apoptosis, PI3K-Akt signaling pathway were regualted to achieve the treatment of myocardial ischemia disease.

目的 利用分析各种浓度环氧化酶-2(COX-2)特异度抑制剂塞来昔布对食管癌EC109细胞系的作用,进而对COX-2蛋白表达的影响及对细胞凋亡能力的作用,进一步探讨塞来昔布对食管癌细胞凋亡的作用及机制。方法 使用0 μmol/L、20 μmol/L、60 μmol/L、100 μmol/L四个浓度的塞来昔布处理EC109细胞24 h,酶联免疫吸附剂测定(ELISA)法测定COX-2蛋白表达;流式细胞仪测定EC109细胞凋亡情况。结果 与0 μmol/L塞来昔布组比较,20 μmol/L、60 μmol/L、100 μmol/L塞来昔布组EC109细胞内COX-2蛋白表达不断降低(1.581±0.116;1.226±0.089,0.846±0.076,0.521±0.082)(P<0.05);而细胞凋亡率逐步上升(1.700±0.557,13.400±1.735,18.766±1.301,28.100±1.997)(P<0.05)药物浓度依赖于梯度。结论 塞来昔布是一种COX-2抑制剂,可能以浓度梯度的形式抑制COX-2蛋白的表达,从而促进EC109细胞的凋亡。

Objective The effects of celecoxib, a specific COX-2 inhibitor at various concentrations, on EC109 cell line of esophageal cancer were analyzed, and the effect and mechanism of celecoxib on apoptosis of esophageal carcinoma cells were further studied. Methods EC109 cells were treated with celecoxib at concentrations of 0 μmol/L, 20 μmol/L, 60 μmol/L and 100 μmol/L for 24 h. The protein of COX-2 in EC109 cells was determined by enzyme-linked immunosorbent assay (ELISA). Assay of EC109 cell apoptosis were determined by flow cytometry. Results Compared with the 0μmol/L celecoxib group, the expression of COX-2 protein in EC109 cells of 20μmol/L, 60μmol/L, 100μmol/L celecoxib group gradually decreased(1.581±0.116; 1.226±0.089, 0.846± 0.076, 0.521±0.082) (P<0.05); and the apoptotic rate gradually increased (1.700±0.557; 13.400±1.735, 18.766±1.301, 28.100±1.997) (P<0.05) in a drug concentration gradient-dependent manner. Conclusion The COX-2 inhibitor celecoxib may inhibit the expression of COX-2 protein in a concentration gradient and promote the apoptosis of esophageal cancer EC109 cells.