This article reports a case of a 72-year-old male with intrahepatic cholangiocarcinoma who developed acute symptoms—including chest tightness, muscle weakness, ophthalmoplegia, and dyspnea—3 days after receiving the second cycle of adebrelimab, following combination therapy with adebrelimab, apatinib, and tegafur. These complications proved fatal. Laboratory tests showed significant elevation of myocardial injury markers (high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, myoglobin, and creatine kinase). Electrocardiogram showed multi-lead ST-T changes and conduction abnormalities, and neurological examination showed ophthalmoplegia. Immune checkpoint inhibitor-associated myocarditis with myositis/myasthenia gravis overlap syndrome (IM3OS) was highly suspected. Despite immediate drug discontinuation and progressive immunosuppression with corticosteroids and intravenous immune globulin, the patient’s condition worsened, and cardiac arrest occurred on day 9. This case underscores the rapid onset and poor prognosis associated with adebrelimab-induced suspected IM3OS, highlighting the critical need for rigorous baseline assessment, prompt recognition, early initiation of aggressive immunosuppressive therapy, and coordinated multidisciplinary management to prevent or mitigate these potentially life-threatening immune-related adverse events.

[This retracts the article DOI: 10.1016/j.heliyon.2022.e11006.].

ObjectiveSorafenib, a multikinase inhibitor, is currently the standard treatment for advanced liver cancer. However, its application has become limited by the development of drug resistance. We intended to explore the mechanisms underlying the development of sorafenib resistance, therefore identifying an effective strategy to overcome sorafenib resistance remain challenges.MethodsHere, the follow-up of liver cancer patients undergoing sorafenib therapy, as well as animal tumor challenge and treatment were performed. The sorafenib-resistant liver cancer cell lines Huh7/SOR and HepG2/SOR were also established. miRNA and mRNA microarray analyses, TargetScan prediction, dual luciferase reporter assay, RNA pull-down assay, co-mmunoprecipitation (Co-IP) and pull-down assays, a transcription factor-specific NRF2 assay, an iron detection assay, a lipid peroxidation quantification assay, a ROS measurement assay, and GSH/GSSG and GSH-px standard quantitative assays were used.ResultsWe showed that upregulation of the provirus-integrating site for Moloney murine leukemia virus 3 (Pim-3) predicted poor response and unsatisfactory prognosis in sorafenib-treated liver cancer patients. Similarly, Pim-3 expression was positively associated with sorafenib resistance in liver cancer cells. Furthermore, microRNA-936 (miR-936) targeted the 3’-noncoding region (3'-UTR) of Pim-3 but exhibited lower expression in sorafenib-resistant liver cancer cells than in their parental cells. The high expression of Pim-3 mediated by miR-936 insufficiency activated the ANKRD18A/Src/NRF2 pathway which rearranged the expression of the indicated markers involved in iron distribution and lipid peroxidation homeostasis. MiR-936 overexpression and GV102-Pim-3-shRNA significantly attenuated the activity of the ANKRD18A/Src/NRF2 pathway to decrease the expression of Ankyrin repeat domain-containing protein 18A (ANKRD18A), Src, and Nuclear factor (erythroid-derived 2)-like 2 (NRF2), especially decreasing NRF2 nuclear retention and transcriptional activity. The transcriptional activity of NRF2 prompted cell ferroptosis because the transfection of miR-936 mimics, GV102-Pim-3-shRNA and GV102-NRF2-shRNA plasmid increased the expression of transferrin receptor 1 (TFR1) and divalent metal transporter 1 (DMT1) but decreased the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1), thus facilitating the accumulation of intracellular Fe2+, lipid peroxides, and reactive oxygen species (ROS) but reducing the glutathione (GSH) level. Moreover, the elevated expression of Pim-3, resulting from the absence of miR-936 enhances sorafenib resistance in liver cancer by inhibiting cell ferroptosis.ConclusionPim-3 can be regarded as a target in the treatment of sorafenib-resistant liver cancer.

Cancers have become the second leading cause of death worldwide, following cardiovascular diseases.Traditional anti- cancer strategies, including radiotherapy chemotherapy, surgery, and targeted therapies, have been widely used but are often reassessed due to their significant side effects and relatively low cure rate. Recently, the development of novel formulations for anti-tumor drugs has gained considerable attention, marking a pivotal step forward in cancer treatment advancements. These innovative formulations aim to enhance the therapeutic efficacy of anti-tumor drugs by employing advanced drug formulation technologies and delivery systems. In particular, nano-drug delivery systems (NDDS) have emerged as a promising approach to improve drug targeting, reduce side effects, and overcome drug resistance. This review highlights recent progress in NDDS for anti-tumor drug development and explores the future prospects of these advanced formulations in improving cancer treatment outcomes.

目的 观察1例急性淋巴细胞白血病(ALL)患儿接受4周期大剂量甲氨蝶呤(HDMTX)巩固化疗的经过,探讨在治疗儿童ALL中质子泵抑制剂(PPI)延迟HDMTX排泄的解决方案和药学监护.方法 通过监测MTX血药浓度指导亚叶酸钙解救,分析患儿使用泮托拉唑延迟HDMTX化疗排泄的情况.结果 本案例中,患儿第1周期未出现HDMTX延迟排泄,第2、3周期出现了明显的延迟排泄,并发生了相关不良反应事件(肝损害、黏膜炎).第4周期采用西咪替丁替代泮托拉唑后未发生HDMTX延迟排泄.结论 PPIs可致HDMTX延迟排泄风险增加,H2受体拮抗剂(H2RA)在降低HDMTX延迟排泄风险方面可能优于PPIs.

目的 基于美国食品药品监督管理局不良事件报告系统(FAERS)数据库对瑞波西利不良事件(ADE)进行分析,为临床安全用药提供参考.方法 通过访问FAERS数据库,检索 2017年 3月 13 日—2023年 3 月31 日瑞波西利的ADE的数据.采用报告比值比(ROR)法联合贝叶斯可信区间递进神经网络法(BCPNN)进行信号挖掘,分析ADE的发生情况.结果 共获得371 个ADE信号,涉及 23 个系统器官类别(SOC),收集报告 30 999 份.主要上报国家是美国;涉及的SOC主要包括各类检查、血液及淋巴系统疾病、全身性疾病及给药部位各种反应、良性与恶性及性质不明的肿瘤、呼吸系统与胸及纵膈疾病等.最常报告的ADE信号包括中性粒细胞减少症、白细胞计数降低、脱发、食欲减退、便秘等.说明书未收录的ADE如大红细胞症、丹毒、日光性雀斑样痣、免疫功能降低等 26 个可疑信号需给予关注.结论 瑞波西利在真实世界中常见的ADE与说明书一致,但也存在一些新的疑似ADE,临床用药时应予以重视.

1病例资料 患者,男,71岁,因"全身散在红色小丘疹,口腔溃疡伴疼痛5 d",于2022年6月15日收住青岛大学附属医院肿瘤科.患者于2022年5月因"发作性胸背疼痛1月余"就诊,经胸部CT及右肺占位穿刺活检,确诊为右肺鳞状细胞癌,临床分期cT3N2M0 ⅢB期.

卡瑞利珠单抗是一种免疫治疗药物,肿瘤患者在临床使用过程中发生反应性皮肤毛细血管增生症(reactive cutane-ous capillary endothelial proliferation,RCCEP)概率较高,生活质量和样貌特征受到影响,产生恐慌心理,治疗积极性降低.该文从RCCEP的临床表现、分级标准、发病机制等多角度进行阐述,综述了 RCCEP预后治疗的各类方案,以提高患者使用卡瑞利珠单抗的依从性,为临床治疗提供参考.

Malus toringoides (Rehd.) Hughes, as a traditional medicinal and edible plant used in Tibet, China, is used to treat hypertension, hyperlipidemia, and liver diseases. In recent decades, excessive fructose intake with diet has greatly increased the occurrence of a series of metabolic diseases including obesity, insulin resistance, hypertension, and hyperlipidemia. The present study was designed to investigate the effects of an ethanol extract of M. toringoides (EMT) on glucose and lipid metabolism and liver injury in high fructose-induced mice. The C57BL/6J male mice were orally administrated with 30% fructose solution for 8 weeks, and EMT was given orally for another 8 weeks. The level of liver lipids related parameters, hepatic oxidative stress, and inflammatory mediators was detected by the kits. The improving effects of EMT on liver injury and lipid accumulation of mice were observed by hematoxylin and eosin staining and Oil Red O staining. In vitro, the hypolipidemic effect of EMT on palmitic acid-induced HepG2 cells was detected by the kits and Oil Red O staining. Our results showed that EMT has the hypolipidemic effect in vivo and in vitro, and can improve liver injury caused by fructose intake though ameliorating oxidative stress and inflammatory responses. Thus, we suggested that EMT may be a candidate therapeutic agent to improve a series of metabolic diseases including obesity, insulin resistance, and hyperlipidemia. PRACTICAL APPLICATIONS: Our study was aimed to find a novel candidate drug for liver diseases using natural products. We assessed the protective effects of Malus toringoides (Rehd.) Hughes in the pathogenesis of glucose and lipid metabolism. In vivo, the plant significantly improved the disorder of blood lipid and blood glucose, and liver injury in mice induced by fructose, and in vitro, this plant significantly improved the lipid accumulation of HepG2 cells induced by palmitic acid. To sum up, our studies suggested that the plant may be beneficial in the prevention and management of diet-induced abnormal glucose and lipid metabolism and liver diseases. Therefore, it will be a candidate therapeutic agent to improve liver diseases.

目的 促进肿瘤内科止吐药物和质子泵抑制剂的合理使用.方法 以循证医学为基础建立药物治疗临床路径,采用戴明环(PDCA)循环法进行行政干预,完善止吐药物和质子泵抑制剂用药路径管理模式.结果 药物治疗临床路径实施后,肿瘤内科5-羟色胺3(5-HT3)受体拮抗剂和质子泵抑制剂的销售金额、人均药费明显减少,用药频度和使用强度均显著下降.结论 建立药物治疗临床路径管理新模式,为合理用药精细化管理提供了新思路.

目的 探讨儿童实体器官移植受者耐氨曲南的产金属β-内酰胺酶(MBL)肠杆菌科细菌感染的治疗方案.方法 回顾分析1例婴儿肝移植术后耐氨曲南的产MBL肺炎克雷伯菌致腹腔感染的临床资料.患儿术后发生腹腔感染,致病菌为产MBL肺炎克雷伯菌,药敏结果提示对氨曲南耐药.初始方案基于药敏结果选用了多黏菌素B联合替加环素的方案,治疗效果不佳,同时出现病情反复和休克性花斑.临床药师协助临床医师制定头孢他啶阿维巴坦0.5 g,q8 h联合氨曲南0.18 g,q6 h的治疗方案;同时复习国内外相关文献,总结实体器官移植术后产MBL肠杆菌科细菌感染的治疗方案.结果 与结论该患儿最终使用头孢他啶阿维巴坦联合氨曲南成功治愈出院.多篇国外文献报道头孢他啶阿维巴坦联合氨曲南可以有效治疗器官移植患者因耐氨曲南的产MBL肠杆菌科细菌导致的感染,该方案有望成为儿童实体器官移植受者该耐药菌感染的有效治疗方案.

基于网络药理学挖掘扶正调理液的分子作用机制,应用BATMAN-TCM在线分析平台预测扶正调理液潜在靶点并构建化合物-靶点-通路-疾病相互作用网络图;应用STRING数据库构建关键靶点蛋白质-蛋白质相互作用网络,基于基因本体(gene ontology,GO)、Reactome、京都基因与基因组百科全书数据库(Kyoto encyclopedia of genes and genomes,KEGG)进行生物通路富集分析;研究扶正调理液对S180荷瘤小鼠体重、进食的影响,计算肿瘤抑制率、胸腺和脾脏指数.结果 表明:扶正调理液的靶点网络主要涉及癌症(非特异性)、疼痛、乳腺癌、心血管疾病、炎症反应、前列腺癌、抑郁等疾病;涉及关键靶点如OPRK1、NR3C1、NR3C2、ADORA1、ESR1等;GO富集分析涉及细胞溶质、细胞质膜、氧化还原酶活性、跨膜转运蛋白活性、细胞氨基酸等小分子代谢过程;Reactome通路富集分析涉及神经元系统、跨化学突触的传递、神经递质受体和突触后信号传递等;KEGG通路富集分析涉及神经活动配体-受体相互作用、钙信号通路、血清素能突触、味觉转导、氨基酸代谢、唾液分泌等.动物实验结果显示:低、高剂量组小鼠的进食量、精神状态和被毛的光泽度优于阳性组及阴性组;高剂量组28 d体质量增长率显著高;低剂量、高剂量及阳性组的肿瘤抑制率分别为8.73％、19.54％、47.89％;低剂量组和高剂量组的胸腺指数低于阳性组但显著高于阴性组;高剂量组的脾脏指数显著低于阳性组.本研究提示扶正调理液可能通过影响关键靶点基因的表达,介导神经活动配体-受体相互作用、钙信号通路、血清素能突触、味觉转导、氨基酸代谢、唾液分泌等信号通路,改善焦虑、抑郁等负面心理状态,提高睡眠质量,减轻疲劳,改善食欲和营养状况,增强免疫功能,改善脾脏肿大和胸腺萎缩的状态,增强荷瘤小鼠免疫功能,抑制肿瘤的进展,体现中药复方的多靶点和整体性的作用特点,为进一步研究扶正调理液的分子作用机制提供新思路.

Combination chemotherapy of pemetrexed and carboplatin is a standard treatment approach for non-small cell lung cancer (NSCLC). However, no prior reports have described cardiotoxicity associated with this therapeutic combination or sinus arrhythmia in oncological contexts. Here, we report the case of a 44-year-old female NSCLC patient that suffered from sinus arrhythmia following combined chemotherapeutic treatment with pemetrexed and carboplatin. The patient was successfully treated under medical guidance, and the condition was effectively reversed following the discontinuation of this chemotherapeutic regimen and medication prescribing. Overall, this represents a rare case of sinus arrhythmia in NSCLC patient during the first cycle of combined chemotherapy with pemetrexed and carboplatin. However, a putative etiological basis for this rare clinical entity remains to be established.

Tumorigenesis refers to the process of clonal dysplasia that occurs due to the collapse of normal growth regulation in cells caused by the action of various carcinogenic factors. These "successful" tumor cells pass on the genetic templates to their generations in evolutionary terms, but they also constantly adapt to ever-changing host environments. A unique peculiarity known as intratumor heterogeneity (ITH) is extensively involved in tumor development, metastasis, chemoresistance, and immune escape. An understanding of ITH is urgently required to identify the diversity and complexity of the tumor microenvironment (TME), but achieving this understanding has been a challenge. Single-cell sequencing (SCS) is a powerful tool that can gauge the distribution of genomic sequences in a single cell and the genetic variability among tumor cells, which can improve the understanding of ITH. SCS provides fundamental ideas about existing diversity in specific TMEs, thus improving cancer diagnosis and prognosis prediction, as well as improving the monitoring of therapeutic response. Herein, we will discuss advances in SCS and review SCS application in tumors based on current evidence.

Background: Malus toringoides (Rehd.) Hughes, as a traditional medicinal and edible plant used in Tibet, China, is used to treat hypertension, hyperlipemia and liver diseases. This present study was designed to investigate the effects of ethanol extract of M. toringoides (EMT) on metabolic syndrome (MS) and liver injury in high-fructose-induced mice. Methods: The C57BL/6J male mice were divided into five groups (n=8). Con group was drunk with standard water, Fru group and the other three with 30% high-fructose water for 8 weeks. EMT (195 mg/kg, 390 mg/kg, 780 mg/kg) was administered to each of high fructose groups simultaneously. Glucose tolerance tests (GTT) were performed. Blood samples were collected from eyeball. The mice were euthanized. Liver and epididymal fat were weighed. The palmitic acid (PA)-induced HepG2 cells were used to evaluate the protective effect of EMT on liver lipid accumulation. Results: The administration of EMT is helpful to maintain near normal body weight, blood glucose, insulin, organ index, glucose tolerance, and serum levels of TC, TG, LDL-C, HDL-C, Apo-B, and Apo-A1 (P < 0.05 or P < 0.01). EMT treatment significantly improved liver injury by the down-regulation of liver lipid accumulation, oxidative stress and inflammatory mediators in high-fructose-induced mice (P < 0.05 or P < 0.01). In vitro , EMT (25 µg/mL-200 µg/mL) significantly decreased lipid droplet accumulation and TG content in PA-induced HepG2 (P < 0.05 or P < 0.01). Conclusion: EMT can obviously improve high fructose-induced MS in mice. In vitro , EMT can inhibit PA-induced lipid accumulation in HepG2 cells.which may emphasizes the use of M. toringoides supplementation in everyday life of over-weighted persons and opens perspectives for clinical trials.

Cancer is one of the most serious diseases that are harmful to human health. Systemic chemotherapy is an optimal therapeutic strategy for the treatment of cancer, but great difficulty has been encountered in its administration in the form of multidrug resistance (MDR). As an enzyme on the outer cell surface, CD13 is documented to be involved in the MDR development of tumor cells. In this review, we will focus on the role of CD13 in MDR generation based on the current evidence.

A pterygium is generally believed to be a chronic inflammatory lesion caused by external stimuli that develops from the conjunctiva and grows onto the cornea. Simple bare sclera excision is the most commonly used method to treat pterygium. However, the high postoperative recurrence rate of pterygium remains a persistent challenge. Mitomycin C (MMC) is an antineoplastic antibiotic that inhibits DNA, RNA, and protein synthesis. In recent years, although MMC has proven useful for the treatment of pterygium, its application has been controversial because of its clear toxicity and the possibility of ocular complications. In the current study, we prospectively recruited patients to receive or not receive a local injection of MMC (0.4 mg/ml). Follow-up was conducted with the patients to determine the postoperative recurrence rate of pterygium and/or to observe any ocular complications. The remarkable results demonstrated that MMC can decrease the postoperative recurrence rate of pterygium without leading to serious eye complications. Further results indicated that MMC can inhibit the activation of the NLRP3 inflammatory signalling pathway and thus downregulate the expression of downstream molecules, including IL-18 and IL-1 β . MMC also reduced the expression of inflammatory factors TGF- β 1, VEGF, and IL-6. In addition to influencing these factors, MMC suppressed neovascularization and the proliferation of corneal fibroblasts to effectively reduce the recurrence rate of pterygium. Taken together, our results provide a theoretical basis for the development of prevention and treatment strategies for pterygium and suggest that MMC is highly effective as an adjunctive treatment after excision of primary pterygia.

病例:患者,男,79 岁.2017 年8 月30 日因"突发右侧肢体活动不灵1 天"入院.近2 天咳嗽咳痰,黄色粘痰,能咳出,并有发热,体温最高达38.3℃.既往脑梗死病史5 年,心动过缓病史10 年,行心脏起搏器置入术,长期口服阿司匹林、阿托伐他汀.入院查体:体温(T)38.3℃,血压(BP)129/78 mmHg,脉搏(P)62 次/ 分,呼吸(R)16 次/ 分,双肺呼吸音粗,可及散在哮鸣音,左侧肢体肌力V 级,右侧肢体肌力IV 级,四肢肌张力正常.右侧指鼻试验及跟膝胫试验欠稳准.生化显示:谷草转氨酶(AST)47.0 U·L-1,谷丙转氨酶(ALT)38.0 U·L-1,肌酸激酶(CK)91.0 U·L-1,肌酐113.0μmol·L-1.入院诊断为:脑梗死、肺部感染.

中韩两国虽然拥有各自的文化体系,但因为历史、地理等种种原因,朝鲜半岛一直受到中华文化的影响,其影响关系甚至可以追溯到上古时期.所以在有关本民族的英雄人物文学创造方面也存在着一定的相似性;又因各国的具体情况差异性,因此在某些方面又有着各自的特点.本篇论文以中国周朝始祖后稷和朝鲜半岛的朱蒙为主要研究对象,结合有关两者的神话传说,以其他古籍文献资料作为补充,通过对比研究两者之间存在的相似与差异,探讨中韩两国上古文学渊源.

目的 观察并探讨药学干预对抗生素临床合理应用的影响.方法 选取144例来我院2016年8月～2018年8月期间就诊的患者,随机将患者按照住院号分为实验组与对照组,每组患者人数各72例,对照组与实验组患者分别给予常规抗生素管理及药物干预下实施抗生素管理,对比两组患者抗生素使用情况.结果 实验组患者抗生素使用种类、合理用药率及不良反应发生率均显著优于对照组,结果间具有显著差异,具有统计学意义,P<0.05.结论 药学干预下实施抗生素管理具有显著临床效果,能够有效减少抗生素使用,减轻患者的经济负担.