The development of multifunctional nanoplatforms capable of enhancing the efficacy and precision of cancer radiochemotherapy remains a significant clinical need. Here, we report a dual-targeted cerium-based metal-organic framework nanoplatform (Pt@Ce-MOF-RGD/FA) designed for synergistic radiosensitization and chemotherapeutic delivery in breast cancer. The Ce-MOF core acts as a reactive oxygen species (ROS) amplifier under radiotherapy, while encapsulated cisplatin (Pt) serves as a chemotherapeutic agent. Surface modification with RGD and folic acid (FA) enables active targeting of tumor cells via αvβ3 integrin and folate receptor pathways. Comprehensive physicochemical characterization confirmed successful construction of the nanocomposite. In vitro, Pt@Ce-MOF-RGD/FA exhibited potent cytotoxicity, enhanced cellular uptake, inhibition of tumor cell migration, and robust ROS generation and mitochondrial membrane depolarization. In vivo fluorescence imaging demonstrated superior tumor accumulation of the dual-ligand-modified formulation. Under radiotherapy, Pt@Ce-MOF-RGD/FA achieved significant tumor growth suppression in a 4T1 murine breast cancer model without inducing systemic toxicity, as confirmed by blood biochemistry, hematological analysis, and histopathology. Collectively, this work presents a rationally engineered nanoplatform with precise tumor targeting, efficient drug delivery, and enhanced radiosensitization, offering a promising strategy for safe and effective cancer treatment.
An important factor influencing the prognosis of ischemic stroke is impairment of the blood-brain barrier (BBB). Additionally, oxidative stress and inflammation contribute significantly to the breakdown of the BBB during ischemic stroke reperfusion. Strong evidence suggested that Aldehyde dehydrogenase 2 (ALDH2) may have protective properties and reduce oxidative stress and inflammatory reactions in neurological conditions. Therefore, in order to examine the impact of ALDH2 on BBB integrity after ischemia/reperfusion (I/R) damage, we constructed the cerebral artery occlusion/reperfusion (MCAO/R) model and the oxygen–glucose deprivation/reperfusion (OGD/R) model. According to our findings, ALDH2 activation enhanced cell viability in bEnd.3 cells treated with OGD/R and reduced infarct area and neurological impairments in MCAO/R animals. Furthermore, both in vitro and in vivo, ALDH2 suppressed inflammation-related factors IL-1β and IL-18, as well as oxidative stress and the expression of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome. In addition, bEnd.3 cells exhibited a reduced reactive oxygen species (ROS) generation function of ALDH2. Moreover, we noticed that ALDH2 boosted the expression of the tight junctions (TJs) zonula occludens-1 (ZO-1) and Occludin to control BBB function. In summary, ALDH2 protected against cerebral I/R injury and BBB destruction, and this protection was related to the ROS/NLRP3 axis.
Aim:The study aimed to culture organoids from tissues of patients with breast cancer (BC) and use the organoids to measure the sensitivity to quercetin and its combination with chemotherapeutic agents. Methods:Four patient-derived organoids (PDOs) of BC were cultured. The proliferative activity and morphology of PDOs were evaluated on different generations and after resuscitation. H&E and immunohistochemical (IHC) staining were used to identify the pathological changes and the expression of biomarkers. The sensitivity to quercetin and chemotherapeutic agents and their combinations were evaluated using adenosine triphosphate (ATP) viability assays. Results:We successfully obtained all PDOs from BC tissues. PDOs preserved their activity and morphology during generation passage. In addition, the pathological changes and expression patterns of estrogen receptor (ER), human epidermal growth factor receptor (HER2), and Ki67 of each PDO were consistent with their original tissues. All four PDOs were highly sensitive to quercetin, and their IC50 values were less than 22 μM. PDOs showed better sensitivity to docetaxel and epirubicin hydrochloride, but less sensitivity to cis-platinum. Combination with quercetin promoted the sensitivity to three chemotherapeutic agents. In particular, the IC50 value of cis-platinum greatly decreased. Conclusion:We successfully established PDOs from patients with BC and demonstrated that quercetin can promote the sensitivity of chemotherapeutic agents in these PDOs.
Background This study aims to assess the effectiveness of neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) in diagnosing cholecystolithiasis with cholecystitis in elderly patients. Additionally, the study seeks to determine the predictive value of preoperative NLR in determining the severity of the condition in this population. Methods This study is a retrospective cohort study, including 160 elderly patients with cholecystolithiasis with cholecystitis (45 cases of simple cholecystitis, 58 cases of suppurative cholecystitis, 57 cases of gangrenous cholecystitis) and 60 cases of normal gallbladder histology. The study collected clinical data of the patients detected the preoperative CRP content, neutrophil, and lymphocyte levels through blood routine tests, and calculated the NLR value. The diagnostic value of NLR and CRP was determined by using the Receiver Operating Characteristic Curve (ROC), and the optimal value of preoperative NLR related to the severity of elderly patients with cholecystolithiasis with cholecystitis was identified. Results This study found that for elderly patients with cholecystolithiasis with cholecystitis, preoperative NLR and CRP levels can be used to distinguish the condition. The critical value for NLR was found to be 2.995 (95% CI, 0.9465–0.9853; P < 0.001) with an area under the ROC curve of 0.9659, while the critical value for CRP was 13.05 (95% CI, 0.9284–0.9830; P < 0.001) with an area under the ROC curve of 0.9557. Both NLR and CRP were found to have equivalent diagnostic abilities. Additionally, the study found that there were significant differences in neutrophil and lymphocyte levels in elderly patients with different severity levels, with NLR increasing as severity increased ( P < 0.001). The study identified cut-off values for preoperative NLR that could distinguish Simple cholecystitis and Purulent cholecystitis, as well as Purulent cholecystitis and Gangrenous cholecystitis in elderly patients with cholecystolithiasis, with respective AUCs of 0.8441 (95% CI: 0.7642–0.9239; P < 0.001) and 0.7886(95% CI: 0.7050–0.8721, P < 0.001), sensitivities of 91.38% and 87.72%, and specificities of 73.33% and 63.79%. Conclusions Preoperative NLR and CRP values can serve as indicators to detect cholecystolithiasis with cholecystitis in elderly patients. Additionally, NLR has been recognized as a potential tool to differentiate the severity of cholecystolithiasis with cholecystitis in the elderly population.
目的 讨论并分析甲状腺微小乳头状癌(PTMC)病人出现头颈部区域转移性淋巴结的危险因素.方法 收集2020年9月至2021年9月蚌埠医学院第一附属医院首次就诊的甲状腺微小乳头状癌病人746例的临床与病理资料,分析其性别、年龄、肿瘤大小、病灶数目、肿瘤侧别、包膜侵犯、合并桥本甲状腺炎(HT)等因素与颈部淋巴结转移的相关性.结果 单因素分析表明,年龄<55岁、男性、多病灶、双侧癌、侵犯包膜、肿瘤长径>5 mm、合并HT的病人与中央区淋巴结转移有关(均P<0.05);男性、多病灶、侵犯包膜、肿瘤长径>5 mm的病人与侧颈区淋巴结转移有关(均P<0.05).多因素分析提示,中央区淋巴结转移的独立危险因素与肿瘤长径>5 mm、多病灶、双侧癌密切相关(均P<0.05);而侧颈区淋巴结转移的独立危险因素与肿瘤长径>5 mm、侵犯包膜和多病灶密切相关(P<0.05).结论 当PTMC病人存在年龄<55岁、男性、肿瘤长径>5 mm、多病灶、双侧癌、侵犯包膜、合并HT等情况时,应对中央区淋巴结进行外科干预,另外可参考颈淋巴结超声、CT等相关辅助检查,有针对地进行侧颈区淋巴结清扫术.
Background The impact of body mass index (BMI) on operative time in transoral endoscopic thyroidectomy vestibular approach (TOETVA) for thyroid cancer is still a subject of debate. This study assessed the impact of BMI on operative time and postoperative complications in patients undergoing TOETVA. Methods The study has been conducted to compare the outcomes of TOETVA in patients with high BMI (≥25) and those with normal BMI (<25). Postoperative outcomes, including operative time, blood lost, recurrent laryngeal nerve (RLN) palsy, hypocalcemia and postoperative pain score, were evaluated. Results A total of 62 patients who underwent TOETVA were included in the study. The high BMI group consisted of 39 patients, while the normal BMI group included 23 patients. No significant differences were observed between the two groups regarding operative time, blood loss, postoperative pain score, and postoperative complications such as recurrent laryngeal nerve (RLN) palsy and hypocalcemia. Conclusions BMI was not significantly associated with operative time and postoperative complications in patients undergoing TOETVA, indicating its safety and feasibility for elevated BMI patients.
Using a meta-analysis approach, we conducted a comprehensive evaluation of the effect of neoadjuvant chemotherapy (NACT) on the incidence of surgical site wound infection during immediate breast reconstruction (IBR) following breast cancer. The aim was to provide evidence-based support for the prevention of wound surgical site infection during IBR after breast cancer surgery. Relevant literature on the effects of NACT on IBR in patients with breast cancer published up until May 2023, was retrieved from various databases, including PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang databases, and China Biology Medicine Database. Two researchers performed the literature screening, data collection, and quality assessment of the included studies independently. The meta-analysis was conducted using Stata version 17.0. Fourteen studies involving 3401 patients (599 in the intervention group and 2802 in the control group) were included in the analysis. The incidence of surgical site infection in the NACT group was higher than that in the control group, but the difference between the two groups was not statistically significant (7.17% vs. 4.85%, odds ratio: 1.02, 95% confidence interval: 0.70-1.50, p = 0.902). These findings suggest that NACT does not increase the risk of surgical site infection during IBR. However, owing to the variation in sample size and literature quality among the included studies, randomised controlled trials are needed to confirm the safety of IBR in patients receiving neoadjuvant chemotherapy.
OBJECTIVEThe purpose of this investigation was to study the expression profile and potential function of circular RNA (circRNA) and long noncoding RNA (lncRNA) in triple-negative breast cancer (TNBC).METHODSRNA sequencing technology was used to detect differentially expressed circRNAs and lncRNAs between TNBC tissues and the adjacent tissue. The potential functions of these different RNAs were analyzed by GO and KEGG enrichment analysis by bioinformatics tools. We also selected and analyzed these key circRNAs and lncRNAs to verify their important functions in TNBC.RESULTSA total of 139 differentially expressed circRNAs and 1001 lncRNAs were obtained. The co-expression analysis showed that the hub lncRNAs (OIP5-AS1, DRAIC) were associated with several tumors and mainly enriched in tumor metastasis. We also screened 5 circRNA-hosting genes (NTRK2, FNTA, BAPGEF2, MGST2, ADH1B) that were associated with the brain-derived neurotrophic factor (BDNF) receptor signaling pathway and cerebral cortex development, as well as AMPK and TGF-β signaling pathway.CONCLUSIONWe identified a large number of differentially expressed circRNAs and lncRNAs, which provide useful insight in understanding TNBC carcinogenesis.
目的 分析蚌埠及周边地区血脂异常患者有机阴离子转运多肽编码基因SLCO1B1和载脂蛋白E(APOE)基因多态性分布及其临床意义.方法 利用聚合酶链反应(PCR)-荧光探针技术,对2020年7-12月在蚌埠医学院第二附属医院就诊的血脂异常患者1530例外周全血基因组中SLCO1B1和APOE基因多态性进行检测,分析其多态性分布情况并统计不同性别基因型分布差异.结果 蚌埠及周边地区患者APOE各基因型所占比例分别为0.52%(E2/E2)、14.12%(E2/E3)、1.96%(E2/E4)、67.12%(E3/E3)、15.10%(E3/E4)、1.18%(E4/E4).其中APOE基因型中疗效较好基因型占比为14.64%,疗效正常基因型占比为69.08%,疗效较差基因型占比为16.28%.蚌埠及周边地区患者SLCO1B1各基因型所占比例分别为4.90%(*1a/*1a)、30.13%(*1a/*1b)、36.60%(*1b/*1b)、0.59%(*1a/*5)、8.24%(*1a/*15),17.32%(*1b/*15)、0.26%(*5/*5),0.13%(*5/*15),1.83%(*15/*15).SLCO1B基因型中正常肌病风险患者占比为71.63%,中度肌病风险患者占比为26.15%,高度肌病风险患者占比为2.22%.基因型频率观察值符合Hardy-Weinberg遗传平衡,具有群体代表性,各基因型组合在男女患者间的分布比较,差异无统计学意义(P>0.05).结论 蚌埠及周边地区血脂异常患者SLCO1B1和APOE的基因多态性分布和性别无关,同时它们会影响他汀类药物的疗效及不良反应风险.对使用他汀类药物患者SLCO1B1和APOE进行基因多态性分析,能够辅助临床制定最合理的给药方案,并能达到精用药物的目的.
目的:检测60S大亚基出核转运GTP酶1(LSG1)在乳腺癌患者癌组织及癌旁组织中的表达,分析其临床意义.方法:选取某院收治且术前未接受任何治疗的15例乳腺癌患者的癌组织及癌旁组织标本,在15例乳腺癌癌组织和对照的癌旁组织中通过实时荧光定量多聚核苷酸链式反应(QRT-PCR)检测LSG1的表达,选取其中6例患者的癌组织及对照癌旁组织标本采用蛋白质印迹法(WB)检测LSG1的表达水平,分析其意义.结果:15例组织中有1例未检测出溶解曲线,故没有数值纳入统计.通过QRT-PCR检测,LSG1基因在乳腺癌癌组织中的表达波动较大,出现两个表达较高的值,致使乳腺癌癌组织整体上的表达高于癌旁组织,差异无统计学意义(P>0.05);WB检测中与对照癌旁组织比较,乳腺癌组织中LSG1蛋白表达明显增加,差异有统计学意义(P<0.01).结论:本次研究证实了LSG1基因在乳腺癌癌组织和蛋白水平的高表达,提示乳腺癌患者预后不良,可能作为乳腺癌新的治疗靶点.
目的:探讨高血压病人降压药物代谢酶基因位点CYP2C9*3(1075A>C)、CYP2D6*10(100C>T)、CYP3A5*3(6986A>G)和药物作用靶点基因位点AGTR1(1166 A>C)、ACE(I/D)、ADRB1(1165G>C)、NPPA(2238T>C)的基因型分布频率.为安徽蚌埠地区高血压病人β受体阻滞剂、血管紧张素受体拮抗剂、血管紧张素转换酶抑制剂、钙离子拮抗剂、利尿剂五大类降压药物的个性化用药提供理论基础.方法:使用PCR熔解曲线法检测2020年1-12月住院的879例高血压病人的药物基因位点多态性,对各基因位点的分型频率进行分析.结果:879例高血压病人AGTR1(1166A>C)基因位点的野生型、杂合突变型、纯合突变型的频率分别为88.74%、10.92%、0.34%;ADRB1(1165G>C)基因位点的野生型、杂合突变型、纯合突变型的频率分别为5.23%、35.38%、59.39%;ACE(I/D)基因位点的野生型、杂合突变型、纯合突变型的频率分别为40.73%、43.12%、16.15%;NPPA(2238T>C)基因位点的野生型、杂合突变型、纯合突变型的频率分别为98.63%、1.37%、0%;CYP2C9*3(1075A>C)基因位点的野生型、杂合突变型、纯合突变型的频率分别为91.81%、7.96%、0.23%;CYP2D6*10(100C>T)基因位点的野生型、杂合突变型、纯合突变型的频率分别为25.94%、45.73%、28.33%;CYP3A5*3(6986A>G)基因位点的野生型、杂合突变型、纯合突变型的频率分别为7.17%、39.70%、53.13%.其中,CYP2C9*3(1075A>C)基因位点基因型在男性与女性病人中的分布差异有统计学意义(P<0.05).CYP2C9*3等位基因多态性在男性和女性病人的分布差异有统计学意义(P<0.05).CYP2D6*10等位基因多态性在男性和女性病人的分布差异有统计学意义(P<0.05).结论:获得安徽蚌埠地区原发性高血压人群的高血压药物相关的基因多态性分布频率的数据,为建立病人基因库提供了基础,便于后期继续深入研究相关基因位点的多态性在临床中指导的合理用药.
目的:观察对比经腋窝入路免充气全腔镜甲状腺癌根治术和开放甲状腺癌根治术对cN0期甲状腺微小乳头状癌的治疗效果.方法:选取60例cN0期甲状腺微小乳头状癌的临床病理资料,其中经腋窝入路免充气全腔镜甲状腺癌根治术30例(观察组),开放甲状腺癌根治术30例(对照组),对比2种术式的临床疗效.结果:2组中央区淋巴结清扫数、中央区淋巴结转移阳性数、总并发症发生率差异无统计学意义(P>0.05);观察组手术时间、引流液总量、住院时间均较对照组更多,术中出血量少于对照组,术后颈胸部疼痛评分、美容满意度优于对照组,差异均有统计学意义(P<0.01).结论:相比开放甲状腺癌根治术,经腋窝入路免充气全腔镜甲状腺癌根治术治疗cN0期甲状腺微小乳头状癌在保证手术安全性及并发症总发生率的同时,可以降低术后疼痛,极大提高美容满意度.
目的 探讨分化型甲状腺癌术后甲状旁腺功能减退的影响因素,建立分化型甲状腺癌术后甲状旁腺功能减退风险综合预测模型.方法 回顾性分析2018年9月至2019年12月蚌埠医学院第一附属医院肿瘤外科收治的100例分化型甲状腺癌病人的临床资料.(1)根据术后4h外周静脉血甲状旁腺激素值分为减退组(23例)与正常组(77例).对两组指标进行多因素Logistic回归分析,用其中差异有统计学意义的指标构建分化型甲状腺癌术后甲状旁腺功能减退风险综合预测模型,并评估此模型的性能.(2)根据术后6个月外周静脉血甲状旁腺激素值将术后甲状旁腺功能减退病人分为暂时性减退组(17例)和永久性减退组(6例),对两组指标进行比较分析.结果 多因素分析表明,淋巴结清扫方式、原位保留甲状旁腺情况及淋巴结转移情况是术后甲状旁腺功能减退的独立影响因素.术后甲状旁腺功能减退的预测模型为:P=Exp (2.271-2.274X1-1.934X2-1.425X3)/[1+Exp(2.271-2.274X1-1.934X2-1.425X3)],其中X1=淋巴结清扫方式,X2=原位保留甲状旁腺情况,X3=淋巴结转移情况.曲线下面积为86.3%,截点值为0.312,敏感度为80.1%,特异度为85.3%.永久性甲状旁腺功能减退的发生与有效原位保留甲状旁腺情况密切相关.结论 分化型甲状腺癌术后甲状旁腺功能减退综合预测模型对术后甲状旁腺功能减退风险具有较好的预测能力.
目的 探讨PDCA法规范某院氟比洛芬酯注射液用法的效果.方法 分析PDCA法干预前后某院氟比洛芬酯注射液临床的使用情况,总结不合理用药的表现和可能的原因,分析干预后的改进效果.结果 经PDCA法干预后,某院氟比洛芬酯注射液使用的不合理率从整改前的26.47%下降至干预后的11.76%,其中骨科二病区、普外西科等科室的剂量偏大、联合用药、疗程过长等问题明显好转.结论 PDCA法规范某院氟比洛芬酯注射液临床使用效果较好,值得推广.
目的 观察仙灵骨葆胶囊灌胃给药引起大鼠肝损伤的作用及机制研究.方法 将60只SD雄性大鼠随机分为5组:正常组、仙灵骨葆低剂量组[0.27 g/(kg·d)]、仙灵骨葆中剂量组[1.08 g/(kg·d)]、仙灵骨葆高剂量组[2.7 g/(kg·d)]、秋水仙碱组[0.1 mg/(kg·d)],每组12只,连续用药2周后,对血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)和基质金属蛋白酶9(MMP-9)的含量进行分析,并测定肝脏组织匀浆液中的丙二醛(MDA)、超氧化物歧化酶(SOD)的含量及肝组织形态学检查.结果 与正常组相比,仙灵骨葆组大鼠体质量增速显著减缓,肝脏指数降低显著,血清ALT、AST、MMP-9差异显著(P<0.01),肝组织SOD、MDA变化显著(P<0.01),尤以中剂量组较为明显.秋水仙碱组体质量、肝指数、血清及肝组织生化指标均与正常组有显著差别(P<0.01或P<0.05).显微镜下观察到仙灵骨葆组肝细胞排列紊乱,肝细胞有炎性浸润,胞浆疏松、肿胀.结论 仙灵骨葆胶囊对大鼠具有一定的肝损伤作用,大剂量及长期服用应预防其副作用;秋水仙碱因其毒副作用大对在体动物肝脏的作用还有待进一步验证,提示临床服用需提防其肝损伤作用.
同源盒基因Six1是一多基因家族的转录调节因子,与恶性肿瘤的发生发展相关. 异常表达的Six1基因可以通过多种信号通路导致正常细胞的凋亡与增殖失衡,上游调控因子的异常表达可以导致Six1的功能失调,而异常表达的Six1可以作用于其靶基因CyclinA1、TGF-β等,从而促进肿瘤的发生发展.
目的 复方非那沙星温度敏感型原位凝胶滴耳剂的处方优化.方法 以测定相转变温度为依据,考察不同比例的泊洛沙姆407、泊洛沙姆188、聚乙二醇6000、等基质对于凝胶性状、相转变温度等的影响.以能否获得适宜耳用的相转变温度(34℃左右)为依据,运用正交设计法筛选并确定最优处方.结果 制备成有适宜相变温度的复方非那沙星温度敏感型原位凝胶滴耳剂.结论 本实验确定了制备复方非那沙星温度敏感型原位凝胶滴耳剂的最优处方,且泊洛沙姆407、泊洛沙姆188、聚乙二醇6000三种基质的最佳配比为17%∶3%∶1.5%.
目的 探究神经纤毛蛋白(Neuropilin 1,NRP-1)在胃癌组织中的表达及其与患者病理特征以及预后之间的关系.方法 回顾性分析2009年4月—2010年4月在本科采取手术治疗的109例胃癌患者临床病理资料,采用免疫组化方法检测胃癌及癌旁组织中NRP-1的表达水平,进一步分析其与患者临床病理特征以及预后之间的关系.结果 109例患者,61例患者胃癌组织NRP-1高表达,48例低表达;NRP-1的高表达与肿瘤直径、原发灶情况、是否有淋巴结转移、淋巴结转移个数以及组织学分化程度相关(P<0.05);COX回归(比例风险模型)多因素分析结果显示NRP-1的表达情况是影响胃癌患者预后的独立危险因素(P<0.05).结论 一方面,NRP-1在胃癌的进展中对肿瘤起到促进作用,其高表达与胃癌的恶性生物学行为相关;另一方面,NRP-1的高表达与胃癌患者的生存率成负相关,NRP-1可能作为一种用于预测胃癌患者预后的肿瘤标记物.
目的 开展多西他赛处方点评工作,为多西他赛的临床合理应用提供参考.方法 专项处方点评小组依据循证医学证据建立多西他赛合理应用评价标准.采用回顾性分析方法,调取某三甲医院2017年应用多西他赛的住院患者归档病历,逐份详细阅读,依据评价标准进行点评.结果 多西他赛合理应用评价标准的主要内容包括适应证、禁忌证、用法用量、预处理、给药顺序和联合用药等.240份病历中,最常见的不合理应用类型为预处理不合理、存在药物相互作用和适应证不合理.结论 依据评价标准的专项处方点评能够发现多西他赛在临床应用时存在的问题,应制订干预措施,促进临床合理用药.
目的:建立HPLC法测定大鼠血浆药物浓度,探讨不同剂量复方苦参注射液在大鼠体内对多西他赛多次给药后药物代谢动力学的影响.方法:将24只SD大鼠随机分为高、中、低剂量组和对照组,每组6只,大鼠尾静脉注射分别给予2倍临床等效量(3.6 mL/kg)、临床等效量(1.8 mL/kg)、1/2倍临床等效量(0.9 mL/kg)的复方苦参注射液和0.9%氯化钠注射液,连续给药7 d,第7天给予复方苦参注射液或0.9%氯化钠注射液5 min后,注射多西他赛15 mg/kg,按时间点采集血样处理并检测分析,计算药物代谢动力学参数.结果:多次给药后高剂量组、中剂量组AUC、Cmax均低于对照组(P<0.05),低剂量组与对照组差异无统计学意义(P>0.05).结论:复方苦参注射液联合使用多西他赛后血药浓度有所降低,对多西他赛的抑制作用具有剂量依赖性,可为临床用药提供一定参考.