Ligusticum Chuanxiong (Chuanxiong Rhizoma) is used in Traditional Chinese medicine (TCM) and has cardioprotective effects. Trastuzumab improves outcomes in HER2-positive breast cancer, but acquired resistance and cardiotoxicity limit its utility. Current quality-control methods rarely integrate composition with functional efficacy, hindering rational standardization. We developed an efficacy-oriented quality-control strategy that couples HPLC profiling with in vitro bioassays. HPLC profiling of 12 commercial batches identified ten common constituents: tetramethylpyrazine, chlorogenic acid, ferulic acid, senkyunolide I, senkyunolide H, 6″-feruloylspinosin, senkyunolide A, n-butylbenzene, ligustilide, and butenylbenzene. All constituents were evaluated by CCK-8 assay to identify those with both cytotoxic activity against a trastuzumab-resistant HER2-positive breast cancer cell line and protective effects against trastuzumab-induced cardiomyocyte injury. We constructed two Effect-Constituent Indexes (ECIJ for cytotoxicity; ECIH for cardioprotection) by weighting abundances by measured bioactivities. Both indices correlated with experimentally determined potency (ECIJ vs 1/IC50: rJ = 0.727, **P < 0.01; ECIH vs 1/EC50: rH = 0.592, *P < 0.05) and discriminated batches better than single markers. Batch S10 exhibited the strongest dual efficacy (IC50 = 0.6553 mg/mL; EC50 = 0.00288 mg/mL). Molecular docking indicated that bioactive constituents may modulate ferroptosis via interactions with SLC7A11 and FSP1. The integrated ECI framework offers an efficacy-driven quality control approach for Chuanxiong Rhizoma and supports its dual application to enhance antitumor activity while mitigating trastuzumab-induced cardiotoxicity.

Objectives: Reports of traditional Chinese medicine (TCM)-related liver injury have increased over recent years; however, identifying susceptibility-related components and biomarkers remains challenging due to the heterogeneous nature of TCM and idiosyncratic drug-induced liver injury (IDILI). Psoraleae Fructus (PF) and Epimedii Folium (EF), commonly found in TCM prescriptions, have been implicated in IDILI, but their constituents and underlying mechanisms are poorly understood.Methods: In this study, we identified bavachin (Bav) and icariin (Ica) as susceptibility components for IDILI in PF and EF using a TNF-alpha-mediated mouse model. Lipidomics and transcriptomics were used to investigate their related mechanism.Results: Liver biochemistry and histopathology analyses revealed that co-exposure to Bav, Ica, and a non-toxic dose of TNF-alpha prestimulation induced significant liver injury, while Bav and Ica alone did not. Lipidomics identified seven differentially abundant metabolites in the Bav/Ica/TNF-alpha group compared to the Ica/TNF-alpha or Bav/TNF-alpha groups, mainly enriched in alpha-linolenic acid (ALA), arachidonic acid (AA), and linoleic acid (LA) metabolic pathways. Additionally, transcriptomics revealed 49 differentially expressed genes (DEGs) in the Bav/TNF-alpha vs Bav/Ica/TNF-alpha and Ica/TNF-alpha vs Bav/Ica/TNF-alpha groups, primarily associated with the PI3K/AKT/mTOR signaling pathway and sphingolipid metabolism. Integrative lipidomics and transcriptomics analyses identified significant positive correlations between five differential metabolites (DMs) - PC (O-16:0_14:1), PG (22:1_20:3), PI (16:0_14:1), PS (18:0_19:2), and TG (17:0_18:2_22:5) - and ten DEGs - Nr0b2, Btbd19, Btg2, Fam222a, Fam83f, Gtse1, Anln, Gja4, Srrm4, and Zfp13.Conslusions: Collectively, these results suggest that alterations in intracellular metabolism and gene expression levels may contribute to the synergistic induction of IDILI by the incompatible pair Bav and Ica in the presence of TNF-alpha.

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is an effective treatment for chemotherapy-induced neutropenia. However, it can also induce various adverse effects, including fever, bone pain, and other discomforts arising from the abnormal proliferation of blood cells. This study presents an analysis of a case involving a middle-aged patient with small cell lung cancer who exhibited transiently low blood glucose levels without experiencing any symptoms of hypoglycemia following PEG-rhG-CSF treatment. After thorough evaluation by clinicians and pharmacists, the condition was diagnosed as pseudohyperglycemia, a phenomenon distinct from true hyperglycemia. The article provides a pharmaceutical perspective on the contributing factors, mechanisms, and management strategies for pseudohypoglycemia, offering valuable insights for clinical practice.

目的 探讨贝伐珠单抗联合化疗治疗非小细胞肺癌(NSCLC)患者的疗效及不良反应,并分析可能影响贝伐珠单抗治疗效果的影响因素.方法 选取2017年1月至2019年12月中国医学科学院北京协和医学院肿瘤医院接受贝伐珠单抗联合化疗治疗的晚期NSCLC患者为研究对象.采用SPSS 22.0软件进行统计学分析,采用log-rank检验进行单因素分析,Cox回归模型进行多因素分析.结果 共纳入77例贝伐珠单抗联合化疗治疗的NSCLC患者,客观缓解率为27.3%,疾病控制率为67.5%,中位无进展生存期(PFS)为7.0个月;使用前T分期为T1～T2(HR=2.627,P=0.048)、贝伐珠单抗使用时机为化疗第1个周期后(HR=0.214,P=0.018)、贝伐珠单抗使用周期＞4个周期(HR=0.219,P=0.001)是影响患者PFS的独立预后因素.与同期行常规化疗未使用贝伐珠单抗治疗的患者匹配后相比,接受贝伐珠单抗联合化疗治疗的患者出现高血压、出血、蛋白尿及尿素氮的风险增高,但未发生严重的不良反应.结论 贝伐珠单抗联合化疗治疗NSCLC患者疗效确切,安全可控,尤其对于第1个周期化疗后使用贝伐珠单抗、使用周期＞4个周期、T分期越早(T1～T2)的患者使用贝伐珠单抗治疗的效果越好.

目的:比较第三批国家药品集中带量采购中标的卡培他滨仿制药与卡培他滨原研药在真实世界中的安全性与有效性.方法:以 2020 年 11 月至 2021 年 11 月中国医学科学院肿瘤医院使用仿制与原研卡培他滨治疗的患者为研究对象,收集患者人口学特征、治疗相关信息、不良事件发生情况及疗效评价等信息.将患者分为仿制药组和原研药组,进行安全性和有效性评价.结果:纳入研究的患者共 254 例,经倾向性评分匹配后,仿制药组和原研药组各 118 例,两组患者在基本特征及不良反应方面的差异均无统计学意义(P≥0.05).利用一线治疗的病例进行有效性评价,两组患者客观缓解率、疾病控制率的差异均无统计学意义(P=0.05;P=0.196).结论:仿制与原研卡培他滨在有效性和安全性方面的差异无统计学意义.

目的 基于文献计量学方法研究中成药不良反应发生特点及其影响因素,探讨中成药药学监护路径建立中的关键步骤.方法 检索2011年1月1日—2020年12月31日期间知网(China National Knowledge In-frastructure,CNKI)数据库中与中成药的不良反应、不合理应用相关的文献报道,利用SPSS 19.0和VOS viewer软件对文献基本信息、中成药不良反应发生特点及不合理使用情况等信息进行统计、分析.结果 共计纳入111篇文献,发布单位主要为医疗机构(108篇);中成药不良反应数据中女性(54.69％)多于男性,临床表现多以用药24 h内出现(62.31％)的程度一般的过敏反应(38.97％)和消化道反应(21.19％)为主;常见不合理使用情况为用药不适宜(32.7％)及用法用量不适宜(21.79％).结论 中成药不良反应研究多集中在临床表现的描述性分析,缺乏对影响不良反应发生因素的关联性分析;现有数据提示建立中成药药学监护路径时应尽量全程化、分阶段、针对性管理.

目的 比较国产和进口中长链脂肪乳/氨基酸(16)/葡萄糖(16％)注射液的质量.方法 参照国内外同类产品的质量检测标准,测定两厂家生产药品的关键质量指标以及混合后的营养液关键质量指标.用SPSS24统计软件分析检测结果.结果 两厂家产品的各检测指标均符合国家标准规定,其中,国产厂家的过氧化值、甲氧基苯胺值、溶血磷脂酰胆碱、溶血磷脂酰乙醇胺和5-羟甲基糠醛含量等杂质指标均低于进口厂家,差异具有统计学意义.国产药比进口药混合后脂肪乳平均粒径大;但＞5 μm乳粒的百分比却更低.国产药的渗透压浓度约840 mOsmol·L-1,还可于用于外周静脉输注.结论 国产和进口的脂肪乳的质量指标均符合国家标准,且国产脂肪乳的质量更优于进口脂肪乳,能保证患者的用药安全.

Lung cancer ranks as a leading cause of death. Although targeted therapies usually trigger profound initial patient responses, these effects are transient due to drug resistance and severe side effects. Xihuang Pill (XHW) is a popular Chinese medicine formula that might benefit cancer patients when used as a complementary therapy. However, its underlying mechanism when combined with anticancer drugs is not clearly understood. Here, we used an integrated strategy to reveal the regulatory properties of XHW in increasing the antitumor activity of anlotinib in lung cancer. We evaluated the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung carcinoma (LLC). We applied untargeted metabolomics to identify the differences metabolism and found that XHW improved the effects of anlotinib on lung cancer. The components and targets related to the effects of XHW treatment on lung cancer were obtained through network pharmacology. Then, by integrating the biologically active components of XHW and anlotinib as well as the treatment-responsive metabolites and their related targets, an interaction network was constructed to evaluate the combination therapy. Finally, important protein candidates for this response were verified by immunohistochemistry of tumor tissues. The results showed that XHW significantly improved the inhibitory effect of anlotinib on tumor growth in LLC-bearing mice. Additionally, 12 differentially-abundant metabolites were identified by untargeted metabolomics in the XHW/anlotinib group compared with the XHW or anlotinib groups, and they were mainly enriched in fatty acid metabolism, lipid metabolism and amino acid metabolism pathways. Anlotinib, 23 components in Shexiang, 2 components in Niuhuang, 30 components in Ruxiang and 60 components in Moyao work together to act on 30 targets to regulate hexadecanoic acid (also named palmitic acid), linoleic acid, lactosylceramide, adrenaline, arachidonic acid and lysoPC(18:1(9Z)). The results of immunohistochemistry showed that XHW combined with anlotinib reduced the expression of PDGFRA in tumors. Overall, the key metabolites of XHW that enhances the efficacy of anlotinib were regulated by a multicomponent and multitarget interaction network. Our results suggested that anlotinib combined with XHW may be a promising strategy for the treatment of lung cancer.

Background: Recently, several clinical studies have evaluated the first-line use of immune checkpoint inhibitors (ICIs) combined with platinum-doublet chemotherapy in patients with non-squamous non-small cell lung cancer (NSCLC), however, the differences in safety and efficacy between the various types of ICIs still require investigation.In this study, we evaluated the efficacy and safety of the first-line use of ICIs combined with platinum-doublet chemotherapy in patients with non-squamous NSCLC by meta-analysis and indirect comparison.Methods: Literature searches were performed using PubMed, the Cochrane Library, Embase, China Knowledge Resource Integrated Database, and Wanfang Data to identify all relevant randomized clinical trials for non-squamous NSCLC after 2010.Overall survival (OS), progression-free survival (PFS), and adverse effects (AEs) were pooled for meta-analysis and indirect comparison.Subgroup analyses were conducted to examine the factors associated with PFS. Results:The meta-analysis showed that the additional use of ICIs could significantly improve PFS and OS.The indirect comparison showed no significant difference in pembrolizumab + chemotherapy and atezolizumab + chemotherapy in the reducing of disease progression, while a significant difference in restricted mean survival time (RMST) was found between pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy.A significant increase in grade ≥3 AEs was observed with the additional use of atezolizumab combined with chemotherapy.Subgroups including PD-1 status [high (>50%), intermediate (1-49%), and negative (<1%) expression], sex (male and female), smoking status (current or former smoker, and never smoked), liver metastases (with and without), age (>65 and ≤65) and Eastern Cooperative Oncology Group (ECOG) score (ECOG=0 and ECOG=1) were all associated with better PFS.Conclusions: This meta-analysis confirmed the treatment effects of ICIs combined with chemotherapy for non-squamous NSCLC.The pembrolizumab combination group had a greater RMST benefit compared with the atezolizumab combination group.Furthermore, our study also demonstrated a PFS advantage for non-squamous NSCLC using ICIs combined with chemotherapy irrespective of programmed death-ligand 1 (PD-L1) expression level, smoking status, liver metastasis status, sex, age and ECOG score.Due to the significant increase in AEs (> grade 3), more attention should be paid to the additional use of atezolizumab.

目的:通过具体案例解析,探讨肿瘤药学科普作品创作,提高肿瘤药学科普创作能力.方法:以文章类、表演类、视频类科普作品为例,从作品设计宗旨出发对肿瘤药学科普作品的创意、内容选择、设计、制作过程及注意事项等进行深入剖析,总结肿瘤药学科普创作的特点和难点、作品内容选择的注意事项及创作常用工具和手段.结果:肿瘤药学科普创作中应注意的五大要素是:科学性、思想性、通俗性、艺术性和技巧性.由于肿瘤患者对疾病认识和感受的特殊性,肿瘤药学科普创作最大的难点是在整体氛围上既不能显得沉重,也不能过于轻松.克服该难点可以通过文章总结的"四个避免"和"四个多用"来实现.结论:在肿瘤药学科普创作中充分考虑"五大要素",注意"四个避免"和"四个多用",充分利用现代化工具和手段,有助于创作出内容充实、形式生动、人文色彩浓厚的肿瘤药学科普作品,体现肿瘤专科药师的服务价值和温度.

Objective:To compare the efficacy and safety between the generic pemetrexed produced by Sichuan Huiyu Pharmaceutical Co., LTD and the original pemetrexed produced by Eli Lilly Nederland B.V. in the treatment for patients with non-small cell lung cancer (NSCLC).Methods:The subjects were patients who received generic and original pemetrexed from March 2019 to December 2019 in Cancer Hospital of Chinese Academy of Medical Sciences. Demographic characteristics (age, gender, past history, etc.), treatment-related information (NSCLC stage, treatment regimen, underlying diseases, etc.), occurrence of adverse events, and efficacy evaluation in patients were collected. Patients were divided into the generic group and the original group, and the general situation, clinical use of pemetrexed, and adverse events in patients in the 2 groups were compared. After propensity score matching for 7 variables such as gender, age, body weight, body surface area, Eastern Cooperative Oncology Group (ECOG) score, tumor stage, and standardized chemotherapy dose, the efficacy and safety in patients between the 2 groups after 2 cycles of treatment with generic and original pemetrexed were compared.Results:A total of 182 patients were enrolled in the study, including 85 patients in the generic group and 97 patients in the original group. The differences in age, gender, ECOG score, body weight and body surface area, and underlying chronic diseases between the 2 groups were not statistically significant (all P>0.05). The patients with advanced stage Ⅲ and Ⅳ cancer in the generic group were significantly more than those in the original group [92%(78/85) vs. 79% (77/97), P=0.032]. The proportion of palliative chemotherapy and maintenance chemotherapy in the generic group was higher than that in the original group ( P<0.001). The difference in median dosage between the generic group and the original group was statistically significant [900 (800, 1 000) mg/m 2vs. 800 (800, 900) mg/m 2, P=0.019]. The difference in chemotherapy cycles between the 2 groups was statistically significant [5 (4, 10) vs. 4 (2, 4), P<0.001]. The overall incidence of adverse events and the incidences of bone marrow toxicity and liver toxicity in the generic group were higher than those in the original group ( P=0.018, P=0.037, P=0.018). After propensity score matching, there were 38 patients in both groups, and the differences in the objective response rate, disease control rate and the incidence of adverse events between the 2 groups were not statistically significant [26% (10/38) vs. 32%(12/38), P=0.723; 89% (34/38) vs. 96% (36/38), P=0.674; 47% (18/38) vs. 24%(9/38), P=0.055]. Conclusion:After propensity score matching, the difference in the efficacy and safety between the generic and the original pemetrexed was not significant.

Lung cancer has a rapidly increasing incidence and remains the highest ranked cancer in terms of mortality worldwide. Xihuang Pill(XHW), a famous four-herb traditional Chinese formulation, has been used to treat lung cancer in China for more than 100 years. It is usually prescribed as a complementary and alternative medicine for cancer therapy. However, the main active ingredients of XHW that treat lung cancer and their regulatory effects remain unclear. Here, we revealed modulatory effects effects of XHW on lung cancer in a mouse model of Lewis lung cancer (LLC) by a comprehensive strategy combining network pharmacology with metabolomics. The results demonstrated that XHW inhibited tumour growth in this model. Additionally, 11 differentially expressed metabolites were identified in the XHW group compared to those in the model group or normal group by untargeted metabolomics. They were enriched in amino acid-related metabolic pathways, and the top three pathways were phenylalanine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and aminoacyl-tRNA biosynthesis. A total of 107 active components derived from Niuhuang, Shexiang, Ruxiang and Moyao, directly acted on 13 important targets (NR3C2, AKR1D1, MPO, PNP, NT5E, TAAR1, ADRB2, ADRB1, ADRA1A, ADRA2B, ADRA2A, MAOA and MAOB) to regulate 4 metabolites (L-phenylalanine, l-adrenaline, corticosterone and guanosine). Our results suggested that the key metabolites of XHW involved in the treatment of lung cancer were regulated by a multi-component and multi-target interaction network. This research elucidated the modulatory effect and therapeutic advantages of XHW treatment for lung tumours through an integrated approach.

目的 观察自制珍黄亚微乳喷雾对急性咽炎模型大鼠的治疗作用.方法 将大鼠随机分为5组(模型组、空白组、空白亚微乳组、六神丸组、珍黄亚微乳组),每组6只,除空白组不进行处理外,其他各组通过15％氨水连续喷喉3 d的方法制备大鼠急性咽炎模型;造模成功后,模型组大鼠腹主动脉取血,处死,摘除咽壁组织,备用;空白亚微乳组、六神丸组、珍黄亚微乳组分别给予空白亚微乳、六神丸、珍黄亚微乳等药物治疗4 d,后腹主动脉取血,处死,摘除咽壁组织,备用.观察各组对模型动物病理状态和血清中白细胞介素-1(IL-1)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)表达的影响.结果 与模型组相比,六神丸组、珍黄亚微乳组可明显改善大鼠急性咽炎的炎症病变、同时对模型动物血清中的IL-1、IL-6、TNF-α的表达有抑制作用.结论 珍黄亚微乳对大鼠的急性咽炎有治疗作用,但治疗效果与六神丸没有明显差异性.

目的 研究康莱特注射液临床应用的适宜性,为临床安全用药提供合理依据.方法 采用回顾性研究方法,通过医院信息系统,选取北京中医药大学东方医院2018年1月1日—2018年12月31日期间所有使用康莱特注射液的住院患者信息,利用Clementine 12.0、SPSS 19.0、Excel等统计学软件结合药品说明书,分析康莱特注射液的临床使用情况、不良反应发生率、是否存在不合理用药等内容.结果 与结论 康莱特注射液的用法用量符合说明书要求,在适应证及用药疗程方面稍有偏差.

Background:The features and survival outcome large cell lung cancer(LCLC) are scarce reported due to its low incidence,as a result, the prognoses of LCLC remain unclear.The aim of this study was to describe the demographic and clinical characteristics of large cell lung cancer with a population-base database and find the prognosis factors for cancer-specific survival(CSS) of the LCLC patients.Besides,a nomogram would be developed and independently validated to predict the CSS for LCLC based on the found prognosis factors. Methods: We extracted LCLC patients information from the Surveillance, Epidemiology, and End Results(SEER) database(2005-2014) and summarized the characteristic of the extracted factors.We used the Cox proportional hazards regression to find the prognosis factors for LCLC patients and develop the nomogram based on these in a splitted train cohort from the extracted data.The validation of the developed nomogram would be performed in an independent validation cohort from the extracted data, in which the C-index and the average of the time-dependent area under the receiver operating characteristic curve(time-dependent AUC) for CSS in 1-year, 3-year and 5-year would be calculated.The calibration curves would be drawn to visualize the performance of the established nomogram. Results: In result,4936 patients with LCLC were identified from the SEER database. Nearly half of LCLC patients were diagnosis with stage IV,only approximately 20% of patients was performed surgery.The prognosis factors influence the LCLC patients included age, sex,American Joint Committee on Cancer (AJCC) stage,race,surgery, tumour size and marital status.The calculated C-index was 0.701±0.01,mean time-dependent AUC for CSS in 1-year, 3-year and 5-year was 0.88.The calibrate curve showed that the gap between the predicted and observed CSS for 1-year, 3-year and 5-year was small. Conclusions:Sex,age,race,marital status,AJCC stage, surgery and tumour size are all the independent prognostic factors for CSS of the LCLC.The established nomogram can provide more precise evaluation for the survival of LCLC patients,and help the clinicians to make individual management.

目的:探讨康莱特注射液在肺癌治疗过程中联合用药的合理性,为临床用药提供参考.方法:采用回顾性研究方法,通过医院信息系统,选取2018年北京中医药大学东方医院所有使用康莱特注射液的肺癌患者信息,利用Clementine 12.0、SPSS 19.0及Excel 2010等统计软件,结合药品说明书,分析康莱特注射液在肺癌治疗过程中联合用药的合理性.结果:共收集到150份独立病历中(涉及96例患者),治疗方案主要包括姑息治疗(105份,占70.0％)、化疗(17份,占11.3％)、靶向治疗(16份,占10.7％)及氩氦刀手术治疗(14份,占9.3％,其中2份同时进行化疗).联合用药频率排序居前10位的药品为盐酸氨溴索注射液、多索茶碱注射液、肝素钠注射液、盐酸甲氧氯普胺注射液、消癌平注射液、氯化钾注射液、榄香烯注射液、呋塞米注射液、人血白蛋白和艾迪注射液,其中有3种为抗肿瘤中药注射剂.分析联合用药规则,化疗患者中使用康莱特注射液与止吐药、抗过敏药和抗肿瘤中药注射剂的关联强度较大,姑息治疗患者中使用康莱特注射液与化痰平喘药、营养补充剂的关联强度最大.结论:康莱特注射液在不同肺癌治疗方案中均有较为广泛的临床应用,与康莱特注射液联合应用的药品大部分为预防用药.

Hair loss is a common dermatosis symptom and side-effect in cancer chemotherapeutics. Imiquimod application at mid and late telogen activated the hair follicle stem cells leading to premature hair cycle entry. Based on quinoline structure, a newly synthesized compound 6b displayed proliferation activity in vitro and in vivo through branch chain replacement and triazole ring cyclization. Toll-like receptors (TLRs) are also critical mediators of the immune system, and their activation is linked to various diseases. The present study aimed to expand new agonists within co-crystallization of TLR7 (PDB code: 5GMH); however, biological assays of NF-κB activity and NO-inhibition indicated that five selected compounds were TLR7 antagonists. Molecular docking indicated the binding mode differences: antagonists binding TLR7 in a different direction and interacting with adjacent TLR7 with difficulty in forming dimers.

Lung cancer remains the leading cause of cancer death worldwide, and the current therapy seems to have reached a plateau due to toxicities and acquired resistance. Therefore, exploration of novel therapeutic avenues may be useful. Si Jun Zi Tang (SJZ), a four-herb Chinese medicine formula first described approximately one thousand years, is often prescribed for cancer patients as a complementary therapy. However, whether SJZ benefits cancer patients as well as the main active constituents and its regulatory mechanism in combination with anticancer drugs remains unknown. Here, we investigated the anti-lung cancer potency and underlying mechanisms of the combination of gefitinib plus SJZ in mice with Lewis lung carcinoma (LLC), using histopathology and an integrated strategy of metabolomics and network pharmacology. The results showed that SJZ significantly enhanced gefitinib suppressing tumor growth and inhibiting LLC metastasis in LLC-bearing mice. Furthermore, 9 potential metabolomics biomarkers that differentially expressed in the SJZ/gefitinib group compared to the SJZ group or gefitinib group were identified by untargeted metabolomics, mainly involved three pathways: tricarboxylic acid cycle, tyrosine and tryptophan biosynthesis metabolism and linoleic acid metabolism. Five active ingredients, kaempferol, ginsenoside Rf, caprylic acid, lauric acid and naringenin, acted directly on 9 targets and regulated 4 out of 9 metabolites. Our results indicated that SJZ enhanced the anti-lung cancer effects of gefitinib via the key targets ABCG2, ABCC1, ABAT, GSR, CYP1A2, ALOX5, CYP3A4, PLA2G1B and PLA2G2A and the key metabolites 2-oxoglutarate, taurocholic acid, oxidized glutathione and linoleic acid. This work illustrated the modulatory properties of SJZ, which enhanced the anticancer effects of gefitinib, using metabolomics and network pharmacology analyses, and provided insights into underlying the mechanism the active ingredients of SJZfor the treatment of lung cancer in combination with gefitinib.

In the present study, we developed and validated a rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of lorlatinib in mouse serum and tissue samples, and such a method was successfully applied to investigate the pharmacokinetic study and tissue distribution of lorlatinib after oral administration. Samples were processed with methanol to precipitate protein and extract drugs, and Afatinib-d6 was used as the internal standard (IS). For LC-MS/MS analysis, compounds were separated on a C18 column by gradient elution (0.1% of formic acid and methanol) at 0.5 mL/min in the positive-ion mode with m/z 407.28 [M + H]+ for lorlatinib and m/z 492.10 [M + H]+ for IS. Good linearity was observed within the calibration ranges. Selectivity, accuracy (−6.42% to 8.84%), precision (1.69% to 10.98%), recoveries (91.4% to 115.0%), and matrix effect (84.2% to 110.6%) were all within the acceptable ranges. After oral administration, serum concentration of lorlatinib quickly achieved the maximal concentration (2,705.683 ± 539.779 μg/L) at 0.625 ± 0.231 h. The highest concentration was detected in the liver (3,153.93 ng/100 mg), followed by the stomach (2,159.92 ng/100 mg) and the kidney (548.83 ng/100 mg). In conclusion, a simple and rapid detection method was established and validated for determination of lorlatinib in blood and tissue samples of mouse. The pharmacokinetic study and tissue distribution of lorlatinib were successfully investigated using this method.