Objectives:To systematically evaluate the efficacy and safety of nebulized inhalation vs. intramuscular delivery of interferon α1b (IFN α1b) for paediatric patients with viral respiratory diseases. Methods:A comprehensive search of databases including PubMed, Web of Science, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), and China Biology Medicine disc (Sinomed) was conducted to identify relevant literature on the use of interferon α1b in children. The search timeframe spanned from database inception to April 2025. Results:A total of 16 studies involving 2002 patients were included. The meta-analysis revealed that the overall efficacy rate in the nebulized inhalation group (94.85%) was significantly greater than that in the intramuscular injection group (82.39%) (P < 0.00001). Consistent results were observed in the herpangina and bronchiolitis subgroup analyses (P < 0.0001). With respect to drug safety, the meta-analysis results revealed that the incidence rate of adverse reactions in the nebulized inhalation group (1.58%) was significantly lower than that in the intramuscular injection group (4.60%) (P = 0.003). The studies had no significant publication bias, and sensitivity analysis suggested that the results were reliable. Conclusion:Compared with intramuscular injection, nebulized inhalation significantly increased the efficacy and safety of IFN α1b in treating paediatric patients with viral respiratory diseases. For children with both herpangina and bronchiolitis, nebulized inhalation was more effective; however, no significant difference was found in the incidence of adverse reactions. In the future, multicentre, large-scale randomized controlled trials should be conducted to further validate these conclusions.

Steroid hormones (SHs) have posed a serious threat to ecosystems and human health. The development of rapid assays for the detection of different SHs is urgent for the ecological and human health. However, the rapid detection of SHs residues in the environment is still a challenge due to the wide variety of SHs and their poor electroactivity. Herein, we introduced a novel nonbiological sensing system utilizing sulfobutyl β-cyclodextrin as a recognition unit for the simultaneous and sensitive detection of multiple SHs in water. The mechanism study showed that the sulphonate group in the prepared SBE-β-CD@CdTe/P(L-Arg)/GCE has a high affinity for the Δ4-3-ketone group in SHs, while the hydrophobic cavity could interact with the unsaturated bond of the C-17 side chain of SHs, resulting in a dual recognition system. Further, the analytical performance of this method was evaluated using 30 different substances, including 24 SHs and 6 steroidal analogues. The results showed that this sensor could simultaneously detect a wide range of SHs containing the Δ4-3-ketone group. The sensor was then applied to simultaneously monitor dexamethasone, fluoxymesterone, and chlormadinon in environmental water samples, and the results were satisfactory with detection limits of 4.1 nmol L-1, 3.4 nmol L-1, and 7.7 nmol L-1, respectively. Meanwhile, the SBE-β-CD@CdTe/P(L-Arg) sensing system exhibited a strong specificity for the target substances. Thus, this sensing system enables the rapidly identifying multiple SHs in the aquatic environment and has great potential applications in environmental studies, illicit addition and drug analysis. In addition, this study provides a new idea and theoretical basis for the construction of on-line monitoring method for strong physiologically active components.

Gonadotropin-releasing hormone (GnRH) analogues are widely used polypeptide therapeutics whose clinical utility is limited by pseudo-allergic reactions mediated through histamine release. This study systematically investigated the correlation between GnRH analogue-induced histamine release and the mast cell receptor Mas-related G protein-coupled receptor X2 (MRGPRX2)-a key mediator of drug-induced pseudo-allergic reactions-sing integrated, in vivo, and structural analyses. In vitro experiments demonstrated that GnRH analogues trigger MRGPRX2-dependent Ca2+ mobilization and mast cell degranulation, resulting in dose-dependent increases in β-hexosaminidase, histamine, and tumor necrosis factor α (TNF-α) release. Among the analogues tested, nafarelin exhibited the highest potency, whereas buserelin exhibited the lowest. In vivo, these analogues induced mast cell degranulation and capillary dilation in mouse paw skin, leading to localized pseudo-allergic symptoms (edema and extravasation) that were confirmed to be MRGPRX2-mediated. Molecular docking revealed that the cationic amino acid at position eight of the GnRH analogues bound complementarily to the negatively charged center within the MRGPRX2 ligand-binding pocket, suggesting a mechanistic basis for receptor activation. Functional validation via Arg8-to-Glu substitution in triptorelin significantly attenuated MRGPRX2 activation. Collectively, this work elucidates the MRGPRX2-dependent molecular mechanism underlying GnRH analogue-induced histamine release and provides a foundation for designing safer analogues with reduced adverse effects.

e24102 Background: Objective To introduce the risk of adverse events (AE) of atezolizumab and provide a reference for the safe clinical application of this drug. Methods: Atezolizumab AE reports from January 2014 to December 2023 were collected from the U.S. Food and Drug Administration Adverse Event Reporting System database. A total of 13,312,811 background patients were included in the analysis (adverse events occurred 38,531,848 cases), of which the number of patients in the target drug population was 18,907 (46,135 adverse events occurred). The Reporting Odds Ratio (ROR) method and the Proportional Reporting Ratio (PRR) are used to jointly detect signals. The signal judgment threshold is usually a≥3, the lower limit of the ROR95% confidence interval is greater than 1, and the lower bound of the PRR95% confidence interval is greater than 1. When ROR is combined with PRR (using a ≥ 3, PRR ≥ 2 and chi-square value ≥ 4 as the threshold), the intersection of the detection signals of the two methods is defined as a positive risk signal. The preferred system organ classification (SOC) and preferred term (PT) of the latest version of the MedDRA dictionary were used to classify AEs, and the top 30 PTs with AE signal intensity were selected for analysis. Results: A total of 18,907 AE reports with atezolizumab as the primary suspected drug were collected, (6543 (34.61%) female, 10,092 (53.38%) male, 2,272 (12.02%) unknown gender) involving 3,039 PTs . Calculated using the ROR and PRR combined detection method, there were a total of 827 positive PT signals. The top five risk signals caused by atezolizumab are systemic immune activation (ROR (95% CI) 625.85 (320.40-1222.49), PRR (Chi-Square) 625.65 (5345.58)); Urinary occult blood (ROR (95%CI) 307.38 (129.21-731.24), PRR (Chi-Square) 307.34 (1561.93); polyradiculoneuropathy (ROR (95% CI) 312.84 (82.99-1179.29), PRR (Chi-Square) 312.82 (678.17)); within Secretion toxicity (ROR (95% CI) 171.15 (79.98-366.25), PRR (Chi-Square) 171.12 (1122.69)); hyperprogressive tumors (ROR (95% CI) 124.85 (77.09-202.22), PRR (Chi-Square) 124.80 (2029.72)). The top 5 SOCs were 6788 (14.71%) cases of systemic diseases and various reactions at the administration site, 4889 (10.60%) cases of gastrointestinal system diseases, and 3780 cases of various examinations (8.19%), 3548 (7.69%) cases of respiratory system, chest and mediastinal diseases, and 3457 (7.49%) cases of infections and infectious diseases. Conclusions: The risk signal for autoimmune diseases caused by atezolizumab is relatively strong. It is recommended that clinicians should pay attention to possible autoimmune diseases of various systems during medication.

e24103 Background: Mesenchymal lymphoma kinase (ALK) gene mutation inhibitors are highly effective treatments for ALK-positive lung cancer. We performed a pharmacovigilance analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: A total of 22 quarterly FAERS files from Q4 2018 to Q1 2024 were used. Reports of lorlatinib were screened. A total of 8,193,675 background patients were included in the analysis (2,425,1106 adverse event occurrences), applying the current MedDRA 27.0 analysis.Adverse events were searched by preferred term (PT) level based on case reports in the literature. After filtering duplicate reports, disambiguation analyses detected safety signals by calculating proportionality ratios of reports (prr), ratios of dominance of reports (RORs), empirical Bayesian geometric means, and information components. Results: The number of patients with lorlatinib was 3,146.Of these, 64 (2.03%) were life-threatening adverse events, 716 (22.76%) were hospitalised due to adverse events, 49 (1.56%) were disabled, and 1021 (32.45%) died. Four methods, ROR, PRR, BCPNN, and MGPS, were used in combination to detect signals, and thresholds were set as follows: a ≥ 3, lower limit of the 95% confidence interval of the ROR > 1PRR ≥ 2, chi-square value ≥ 4, IC-2SD > 0, and EBGM05 > 2. A total of 124 positive PT signals were detected, and the top 5 preferred phrases (PTs) in terms of the frequency of lorlatinib risk signals were ranked:Death ROR (95% CI) 5.81 (5.39-6.27), PRR (Chi-Square) 5.44 (2634.70), IC (IC-2SD) 2.44 (2.32), EBGM (EBGM05) 5.43 (5.03); progressive tumours ROR (95% CI) 72.80 (66.60-79.58), PRR(Chi-Square) 68.74(34238.5), IC(IC-2SD) 6.07(5.76), EBGM(EBGM05) 67.00(61.29); blood cholesterol elevation, ROR(95% CI) 26.24(22.15-31.08), PRR(Chi-Square) 25.86 (3244.42), IC (IC-2SD) 4.68 (4.19), EBGM (EBGM05) 25.62 (21.63).Top 3 preferred terms (PT) for lorlatinib-positive signal intensity: very low-density lipoprotein elevation ROR (95% CI) 274.80 (132.58-569.55),PRR (Chi-Square274.56 (1972.86),IC (IC-2SD) 7.96 (2.11),EBGM (EBGM05)248.51 (119.90); Hypercholesterolaemia ROR (95% CI) 113.27 (92.53-138.66),PRR (Chi-Square) 112.08 (10450.5),IC (IC-2SD) 6.75 (5.41),EBGM (EBGM05) 107.50 (87.82);Lipid abnormalities ROR (95% CI) 126.88 (71.06-226.56), PRR (Chi-Square) 126.72 (1427.41), IC (IC-2SD) 6.92 (2.74), EBGM (EBGM05) 120.90 (67.71). Conclusions: The overall adverse effects of lorlatinib are manageable, but the risk of hyperlipidaemia, particularly very low-density lipoprotein elevation, is strong, in addition to adverse effects including death, progressive tumours, impaired consciousness and psychiatric disorders. These signals require further regulatory investigation to determine their significance.

PurposeTo evaluate the cost-effectiveness of sotorasib versus docetaxel in non-small cell lung cancer (NSCLC) patients with KRASG12C mutation from the China and United States’social perspective.Materials and MethodsA Markov model that included three states (progression-free survival, post-progression survival, and death) was developed. Incremental cost-effectiveness ratio (ICER), quality-adjusted life-year (QALY), and incremental QALY were calculated for the two treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagrams were used to present the results. Probabilistic sensitivity analysis was performed with 1,000 Monte Carlo simulations. Assume distributions based on parameter types and randomly sample all parameter distributions each time., The results were presented as cost-effectiveness acceptable curves.ResultsThis economic evaluation of data from the CodeBreak 200 randomized clinical trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compared with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than willingness to pay (WTP), so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50/QALY, which was more than 1 WTP but less than 3 WTP, indicating that the increased cost of sotorasib was acceptable. One-way sensitivity analysis showed that the probability of sotorasib having economic benefits gradually increased when the cost of follow-up examination was reduced in China. And there was no influence on the conclusions within the range of changes in China. When the willingness to pay (WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.ConclusionSotorasib had a cost effect from the perspective in the United States. However, sotorasib had no cost effect from the perspective in China, and only when the WTP exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.

Programmed death receptor-1 monoclonal antibodies (PD-1 mAbs) have been applied in the treatment of different kinds of malignant tumors. However, a streamlined and expedited evaluation method for certain tumor types without approved indications is currently lacking in terms of their expandable applications. In this study, a novel evaluation method for the expandability of PD-1 mAb was established for the first time. Clinical trial data of PD-1 mAb in first-line treatment for advanced gastric cancer were collected for comparison. For the first time, the clinical trial outcomes were analyzed through the entropy weight method and the technique for order preference by similarity to ideal solution (TOPSIS) method to evaluate the effectiveness and safety. The accessibility was assessed using the World Health Organization/Health Action International (WHO/HAI) standard survey method. Combining the results of effectiveness, safety, and accessibility, the recommendation for expandability of PD-1 mAb was provided. Tislelizumab ranks seventh in effectiveness, higher than the chemotherapy group and the pembrolizumab group, and ranks fourth in safety evaluation and first in the combination chemotherapy groups. The annual drug cost of tislelizumab is 0.497 times the annual household income for urban residents of Shaanxi Province. 56.67% of medical institutions are equipped with tislelizumab in Shaanxi Province. These results indicate the promising efficacy and safety profile of tislelizumab in combination with chemotherapy as a first-line treatment option for advanced gastric cancer. Notably, tislelizumab emerges as a more accessible alternative to sintilimab and boasts greater affordability compared to nivolumab and pembrolizumab. Consequently, tislelizumab should be considered a viable option for expandable application in first-line treatment of advanced gastric cancer, contingent upon clinical necessity.

目的 快速评价贝利尤单抗治疗系统性红斑狼疮(SLE)/狼疮性肾炎(LN)的安全性、有效性和经济性,为临床合理用药提供参考.方法 计算机检索Pubmed、Embase、the Cochrane Library、中国期刊全文数据库、万方数据知识服务平台、维普数据库、中国生物医学文献服务系统及卫生技术评估(HTA)相关网站,根据纳入和排除标准由2名研究者独立筛选文献,提取数据,并对纳入文献进行质量评价与定性合成分析.结果 共纳入文献37篇,其中系统评价/meta分析22篇,HTA报告2篇,药物经济学研究13篇;文献总体质量较好.结果 显示,贝利尤单抗可以改善SLE患者的耀斑复燃发生率,提高SLE应答指数,降低SLE活动度评分,减少糖皮质激素使用剂量,提高LN患者的完全缓解率;贝利尤单抗不增加不良事件、严重不良事件及特殊不良事件发生率;在儿童、≥65岁老年人、SLE伴皮肤型红斑狼疮患者中贝利尤单抗可能安全有效;经济学研究结果显示,在多个国家及我国香港地区贝利尤单抗治疗具有成本优势.结论 贝利尤单抗在SLE/LN患者中有良好的安全性和有效性,但药物经济学无中国本土研究,需开展相关研究.

159 Background: To establish a standardized pharmacy service model for PD-1 monoclonal antibodies through a case study of the practice of full pharmacy service for immune checkpoint inhibitors and to explore the effect of clinical pharmacists' participation in the full pharmacy service for PD-1 monoclonal antibodies. Methods: Patients were graded according to age, pathological stage, Carlson co-morbidity index grading and different treatment stages (preoperative neoadjuvant, postoperative adjuvant and advanced first-line, second-line and third-line or above), whether they had concomitant autoimmune diseases and combination drug use (monotherapy, combination chemotherapy, combination targeted or anti-angiogenic drugs, combination chemotherapy + targeted/anti-angiogenic drugs) to establish PD-1 The effect of this pharmacy service model was evaluated by using the immunotherapy treatment of 132 patients in Shaanxi Provincial People's Hospital who were pharmacologically monitored by clinical pharmacists. Results: 132 patients, 91 males and 41 females, 7 patients aged ≥ 70 years with stage IV tumor and Carlson co-morbidity index ≥ 9 scores were subjected to special grade pharmacological monitoring, 1 patient developed immune myocarditis, 1 patient developed immune pneumonia and reactive capillary hyperplasia, which improved after treatment with methylprednisolone, age < 70 years, stage IV tumor, Carlson Primary pharmacological monitoring was performed in 13 patients with co-morbidity index ≥9 points, of which 10 cases (76.9%) had adverse reactions, 3 cases had pulmonary infections and discontinued, 2 cases had severe thrombosis of grade 3 or higher leading to discontinuation, and the others were hyperthyroidism, hypothyroidism, hypocorticism, etc. Secondary monitoring was performed in the other 112 patients, of which 11 cases (9.8%) had adverse reactions The other cases were immune enteritis, immune encephalitis and immune myocardial injury, and most of the adverse reactions occurred in the 5th cycle after drug administration. Conclusions: By establishing a hierarchical pharmacological monitoring model; patients aged <70 years, stage IV tumors, and Carlson co-morbidity index score ≥9 are at high risk for adverse reactions to immunotherapy, and pretreatment of these patients in advance can ensure the safety of patients' medication, improve medication compliance, and improve patients' quality of life.

Objective To establish the assessment for extended application of tislelizumab in the first-line treatment of advanced gastric cancer,so as to provide basis and reference for clinical rational application.Methods Review the litera-ture and collect the data of clinical trials related to PD-1 monoclonal antibody used in the first-line treatment of advanced gastric cancer.Analyze the results of clinical trials by entropy weight method and TOPSIS method,and evaluate the effec-tiveness and safety of tislelizumab in the first-line treatment of advanced gastric cancer.WHO/HAI standard survey meth-od was used to evaluate the accessibility of tislelizumab.Based on the evaluation results of effectiveness,safety and accessi-bility,the opinions on the extended application were given.Results Tislelizumab combined with chemotherapy had good ef-fectiveness,safety and accessibility for first-line treatment of advanced gastric cancer.Its application could be extended when necessary in combination with clinical practice.Conclusion Tislelizumab can be considered as an extended first-line treatment for advanced gastric cancer under appropriate circumstances.

目的 通过循证医学的方法对3个不同厂家利妥昔单抗进行超说明书用药病种药品遴选量化评估,为医疗机构合理用药及药品遴选提供依据.方法 参考《中国医疗机构药品评价与遴选快速指南》,通过收集3个不同厂家的利妥昔单抗(商品名:美罗华?、汉利康?、达伯华?)药学特性、有效性、安全性、经济性、医保属性、基本药物、贮藏条件、药品有效期、全球使用情况和生产企业状况等数据,对利妥昔单抗在类风湿性关节炎(RA)、免疫性血小板减少症(ITP)、肉芽肿性/显微镜下多血管炎(GPA/MPA)中的应用进行遴选量化评估.结果 3种利妥昔单抗治疗RA中,美罗华?得分64,达伯华?得分70,汉利康?得分为72,治疗RA时可优选汉利康?;3种利妥昔单抗治疗ITP及GPA/MPA中,达伯华?得分最高,分别为68及71,治疗ITP及GPA/MPA可优选达伯华.结论 3种利妥昔单抗均可进入医院用药目录,治疗RA推荐汉利康?,治疗GPA/MPA推荐达伯华?,治疗ITP弱推荐达伯华?.

Objective To evaluate the efficacy and safety of EGFR-TKIs combined with radiotherapy for patients with non-small cell lung cancer brain metastases, and to provide reference for the selection of treatment options for patients.

To observe the efficacy and safety of programmed death receptor-1 (PD-1) monoclonal antibody in the treatment of advanced malignant tumors in the real world.

探讨临床药师在抗凝治疗会诊中协助制定抗凝方案并为患者降低出血风险的作用.选取4例会诊使用利伐沙班的病例,重点分析房颤合并短肠综合征患者、肝硬化合并静脉血栓患者选择利伐沙班抗凝的原因,以及当利伐沙班与其他治疗药物存在相互作用并发生出血时,临床药师主动发现、调整方案并监护的过程,4例患者后期随访中未再发生血栓及出血事件,转归良好.临床药师通过个体化的药学服务为患者在抗凝治疗中平衡血栓与出血的风险,保证患者治疗的安全及有效性.

Herein, hyaluronic acid (HA) and β-cyclodextrin (β-CD) is used to form targeted drug delivery platform HCPC/DEX NPs with previously prepared carbon dots (CDs) as cross-linker, dexamethasone (DEX) is loaded for rheumatoid arthritis (RA) treatment. The drug loading capacity of β-CD and M1 macrophage targeting of HA were utilized for efficient delivery of DEX to the inflammatory joints. Because of the environmental responsive degradation of HA, DEX can be released in 24 h and inhibit the inflammatory response in M1 macrophages. The drug loading of NPs is 4.79 %. Cellular uptake evaluation confirmed that NPs can specifically target to M1 macrophages via HA ligands, the uptake of M1 macrophages is 3.7 times that of normal macrophages. In vivo experiments revealed that NPs can accumulate in RA joints to alleviate inflammation and accelerate cartilage healing, the accumulation can be observed in 24 h. The cartilage thickness increased to 0.45 mm after HCPC/DEX NPs treatment, indicating its good RA therapeutic effect. Importantly, this study was the first to utilize the potential acid and reactive oxygen species responsiveness of HA to release drug and prepare M1 macrophage targeting nanodrug for RA treatment, which provides a safe and effective RA therapeutic strategy.

Background:Colorectal carcinoma (CRC) treatment remains severe. Survivin is aberrantly overexpressed in CRC tissues and might be a potential target for CRC treatment. TDB-6 is a new taspine derivative. The purpose of this study is to investigate the inhibitory effect of TDB-6 on CRC and its underlying mechanism.Methods:The MTT assay and xenograft model were utilized to investigate the inhibitory effect of TDB-6 on LoVo cells in vitro and in vivo. Hoechst staining and Annexin-V FITC/PI analysis were conducted to study the effect of TDB-6 on LoVo cell apoptosis. Mitochondrial membrane potential (Δψm) assay was conducted to demonstrated whether TDB-6 could induce mitochondrial-mediated apoptosis of LoVo cells. Western blotting was conducted to investigate the effect of TDB-6 on survivin protein and caspase/Bcl-2/Cyto-C signaling.Results:The results indicated that TDB-6 induced mitochondria-mediated apoptosis and inhibited the proliferation and growth of LoVo cells in vitro and in vivo. Mechanistic investigation utilizing western blotting indicated that TDB-6 inhibited survivin protein expression, and the inhibitory effect was augmented by TDB-6 and YM-155 co-administration, which revealed that TDB-6 might induce apoptosis of LoVo cells by targeted regulation of survivin. TDB-6 also regulated survivin downstream signaling. It significantly increased the protein level of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, cleaved-PARP, and Cyto-C, and decreased the protein level of Bcl-2.Conclusions:TDB-6 might be a promising survivin inhibitor with great potential for CRC treatment.

目的 分析碘克沙醇在血管造影应用中发生药品不良反应(adverse drug reaction,ADR)的特点及规律,为减少临床用药风险提供参考.方法 临床药师对我院心内科2018年7月1日至2019年5月31日使用碘克沙醇的415例患者进行药学监护,询问并记录患者使用碘克沙醇后ADR发生的时间、症状及程度,利用医院信息管理系统(HIS)检索患者其他信息,包括性别、年龄、体重、肌酐值等.结果 415例患者中有359例患者录入ADR相关有效信息,发生ADR的患者共计110例,ADR总体发生率30.64％.其中急发ADR占不良反应总数的14.55％,迟发占85.45％;轻度占73.64％,中度占25.45％,重度占0.91％;按ADR累及系统-器官统计共计181例次,皮肤及其附件损害占25.41％,消化系统占27.62％,神经系统占24.31％,心血管系统占3.87％,呼吸系统占9.39％,泌尿系统占1.10％,全身ADR占8.29％.过敏性休克1例,对比剂所致的急性肾损伤(contrast induced acute kidney injury,CI-AKI)2例.结论 碘克沙醇相关ADR发生率高于既往报道,应加强术前预防评估及各项措施,降低ADR发生率,提高用药安全性.

临床药师参与1例罕见的急性起病并继发噬血细胞综合征的黑热病患者的药学实践,通过多学科急会诊、临床药学小组紧急会诊、重点病患全程药学监护以及诊疗效果的追踪分析,探讨了急诊临床药师的服务模式.该模式可充分发挥急诊药师作用,为急诊患者提供快速、有效、安全、个体化的药学服务,同时为临床治疗积累了经验:对于急性起病、高龄或伴合并症的黑热病患者,初始治疗方案宜选用两性霉素B脂质体.通过践行急诊药学服务模式,对临床药师深入开展急诊药学服务具有一定意义.

Background:Glycolysis is a central metabolic pathway for tumor cells. However, the relationship between glycolysis and the prognosis of gastric cancer (GC) patients is not well established. In this study, we sought to construct a glycolysis-related gene signature for GC.Methods:The messenger ribonucleic acid (mRNA) expression profiles were analyzed using data from The Cancer Genome Atlas (TCGA) database. Glycolysis-related gene sets and pathways were obtained from the Molecular Signatures Database (MSigDB). Subsequently, a prognosis prediction model of the glycolysis-related genes was constructed using Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. An external validation was conducted using data from the Gene Expression Omnibus (GEO) database. Risk scores were also calculated based on the signature. Finally, the correlations between the risk score and overall survival (OS), mutation, immune cell infiltration, immune score, and stromal score were examined in 22 types of infiltrating immune cells.Results:Fifty-five glycolysis-related genes were identified from TCGA database and MSigDB. Using the LASSO and Cox models, 4 novel genes (i.e., VCAN, EFNA3, ADH4, and CLDN9) were identified to construct a gene signature for GC prognosis prediction. The GC patients with low-risk scores had significantly better OS than those with high-risk scores in the training set. Similar results were also found in the independent GEO GSE84437 testing set. Additionally, the degree of cell infiltration in the low-risk group was significantly higher than that in the high-risk group in terms of naive B cells, plasma cells, and T follicular helper cells. In monocytes, M2 macrophages, resting dendritic cells, and resting Mast cells, the degree of infiltration in the high-risk group was significantly higher than that in the low-risk group. The immune score and stromal score of the high-risk group were also significantly higher than those of the low-risk group. Finally, the univariate and multivariate Cox regression analyses showed that 4 glycolysis-related genes were independent prognostic factors for GC.Conclusions:The established 4 glycolysis-related gene signature may serve as a reliable tool for the prognosis of GC patients and provide a potential glycolysis therapeutic target for GC.

The 2017 NCCN Guidelines for NSCLC recommend epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as the first-line treatment for patients with gene-sensitive mutations of pulmonary adenocarcinoma. The TKI combination can effectively inhibit the gene mutations caused by the drug resistance and enhance the antitumor effect. However, more clinical investigations are required of the efficacy and the adverse drug reactions (ADRs) of this combination. A 62-year-old female patient diagnosed as lung adenocarcinoma with brain metastasis, meningeal metastasis, multiple bone metastasis, and liver metastasis was treated with the combination of gefitinib and osimertinib. Evident improvement was observed after 10 days of combined treatment with these tyrosine kinase inhibitors (TKIs), including in the CT features and symptoms. The level of tumor marker CEA decreased significantly after 40 days. However, severe stomatitis occurred after 49 days. By analyzing the relationship between stomatitis and TKI combined treatment based on the temporal correlation, instructions and literature reports, mechanisms, and reaction, we discovered that the combination of the two TKI drugs can increase the incidence and severity of severe stomatitis. Following targeted treatment and drug withdrawal, the patient fully recovered. TKI combination may increase the incidence and severity of stomatitis, suggesting that closely care and timely withdrawal are necessary measures.