Mutations in the structural domain of the epidermal growth factor receptor (EGFR) kinase represent a critical pathogenetic factor in non-small cell lung cancer (NSCLC). Small-molecule EGFR-tyrosine kinase inhibitors (TKIs) serve as first-line therapeutic agents for the treatment of EGFR-mutated NSCLC. But the resistance mutations of EGFR restrict the clinical application of EGFR-TKIs. In this study, we constructed a clinically relevant PC-9 EGFRD19/T790M/C797S cellular model featuring the mutation type within the EGFRD19/T790M/C797S. This model aims to investigate the inhibitory effects of small-molecule EGFR-TKIs and to provide a cellular platform for developing a new generation of innovative drugs that target resistance associated with EGFR mutations.

Objective To study the impacts of curcumin on the proliferation, migration and cisplatin (DDP) resistance of bladder cancer cells by regulating the liver kinase B1-AMP activated protein kinase-microtubule-associated protein 1 light chain 3 (LKB1-AMPK-LC3) signaling pathway. Methods Human bladder cancer cell line T24 was cultured in vitro, and its DDP resistant T24/DDP cells were induced by cisplatin (DDP). After treating T24 and T24/DDP cells with different concentrations of curcumin, the optimal concentration of curcumin was screened by MTT assay. T24 cells were randomly grouped into control group, curcumin group, metformin group, and combination group of curcumin and metformin. After treatment with curcumin and LKB1-AMPK activator metformin, the proliferation, autophagy, migration, and apoptosis of T24 cells in each group were detected by MTT assay, monodansylcadavrine (MDC) fluorescence staining, cell scratch assay, and flow cytometry, respectively. Western blot was used to detect the expression of proteins related to LKB1-AMPK-LC3 signaling pathway in T24 cells of each group. T24/DDP cells were randomly assigned into control group, curcumin group, metformin group, and combination group of curcumin and metformin. Cells were treated with curcumin and metformin according to grouping and treated with different concentrations of DDP simultaneously. Then, the effect of curcumin on the DDP resistance coefficient of T24/DDP cells was detected by MTT assay. T24/DDP cells were randomly grouped into control group, DDP group, combination groups of DDP and curcumin, DDP and metformin, DDP, curcumin and metformi. After treatment with DDP, curcumin, and metformin, the proliferation, autophagy, migration, apoptosis, drug resistance, and the expression of proteins related to LKB1-AMPK-LC3 signaling pathway in T24/DDP cells of each group were detected with the same methods. Results Compared with the control group, the activity of T24 cells, relative number of autophagosomes, migration rate, Phosphorylated-LKB1 (p-LKB1)/LKB1, Phosphorylated-AMPK (p-AMPK)/AMPK, LC3II/LC3I, and the DDP resistance coefficient of T24/DDP cells in the curcumin group were lower, and the apoptosis rate of T24 cells was higher; the changes in various indicators in the metformin group were opposite to those in the curcumin group. Compared with the curcumin group, the activity of T24 cells, relative number of autophagosomes, migration rate, p-LKB1/LKB1, p-AMPK/AMPK, LC3II/LC3I, and the DDP resistance coefficient of T24/DDP cells in the combination group of curcumin and metformin were higher, and the apoptosis rate of T24 cells was lower. Compared with the control group, there were no obvious changes in various indicators of T24/DDP cells in the DDP group. Compared with the control group and DDP group, the viability of T24/DDP cells, relative number of autophagosomes, migration rate, P-glycoprotein (P-gp) protein expression, p-LKB1/LKB1, p-AMPK/AMPK, and LC3II/LC3I in the combination group of DDP and curcumin were lower, and the apoptosis rate of T24/DDP cells was higher; the changes in the above indicators in the combination group of DDP and metformin were opposite to those in the combination group of DDP and curcumin. Compared with the combination group of DDP and curcumin, the viability of T24/DDP cells, relative number of autophagosomes, migration rate, P-gp protein expression, p-LKB1/LKB1, p-AMPK/AMPK, and LC3II/LC3I in the combination group of DDP, curcumin and metformin were higher, and the apoptosis rate of T24/DDP cells was lower. Conclusion Curcumin can reduce the activity of LKB1-AMPK-LC3 signaling pathway, thereby inhibiting autophagy, proliferation and migration of bladder cancer cells, promoting their apoptosis, and weakening their resistance to DDP.

With the widespread application of systemic treatments for hepatocellular carcinoma, liver injury caused by molecular targeted drugs and immune checkpoint inhibitors has become a common clinical problem. The Chinese Society of Hepatology organized relevant domestic experts to summarize and analyze the adverse liver reactions and diagnosis and treatment progress related to systemic treatment of liver cancer at home and abroad, and formulated the "Consensus on the management of liver injury associated with targeted drugs and immune checkpoint inhibitors for hepatocellular carcinoma," aiming to provide reasonable suggestions and decision-making references for clinical physicians in liver disease and related specialties in the monitoring, diagnosis, prevention and treatment of liver injury during the treatment of targeted drugs and immune checkpoint inhibitors for hepatocellular carcinoma, so as to enable more liver cancer patients to benefit from targeted immune therapy.

Immune checkpoint inhibitors (ICPis) significantly improves survival in a number of cancer patients by blocking immunosuppressive molecules and reactivating the function of effector T cells to specifically kil tumor cells. This article reports a case of secondary hypoadrenocorticism caused by programmed death 1 (PD-1) inhibitor related hypophysitis. A 65-year-old male patient received immunotherapy for right lung squamous cell carcinoma invading the chest wall (cT4N2M0) for 4 times. Two weeks after the last immunotherapy treatment, the patient experienced poor appetite and fatigue. Examination results indicated severe hyponatremia, and there was no improvement even after repeated supplementation with high-concentration sodium chloride. After further examination, glucocorticoid supplementation was given to the patient and his clinical symptoms were significantly improved. It is recommended that patients receiving ICPis should be asked in detail about their medical history before initiating treatment, baseline screening should be carried out reasonably, and regular follow-up about endocrine gland hormone and related biochemical indexes after treatment should be carried out. Meanwhile, it is necessary to pay attention to the related symptoms and signs of patients in order to find endocrine gland adverse reactions in time.

Immune checkpoint inhibitors (ICI), as a new type of targeted therapeutic drugs, have demonstrated durable efficacy in cancer treatment. However, some patients receiving ICI treatment may be affected by immune-related adverse events (irAE). Compared with irAE in skin tissues, gastrointestinal system, etc., irAE in the neuro-ophthalmic efferent system are relatively rare. The reported irAE in the neuro-ophthalmic efferent system mainly include myasthenia gravis, orbital extraocular myositis, thyroid-associated ophthalmopathy-like conditions, internuclear ophthalmoplegia, Miller-Fisher syndrome, and cranial nerve adverse events. Exploring the possible mechanisms and potential intervention measures of irAE in the neuro-ophthalmic efferent system is crucial for predicting the risk of irAE in patients, formulating preventive measures, and implementing more effective clinical treatments. This review aims to summarize the occurrence mechanisms, clinical features, and prevention and treatment measures of irAE in the neuro-ophthalmic efferent system, so as to assist ophthalmologists and oncologists in the early diagnosis and management of such patients.

To investigate the effect of genetic polymorphism of MTHFR C677T (rs1801133) on methotrexate (MTX) related toxicity in pediatric mature B-cell lymphoma patients.

To explore the antitumor effect of Inonotus obliquus extract on 4T1 tumor-bearing mice in vivo and its possible mechanism.

This study aims to investigate the effect and mechanism of the herb pair Agrimoniae Herba-Coptidis Rhizoma in inhibiting angiogenesis in the colorectal cancer inflammatory microenvironment by using the method of network pharmacology and the zebrafish model. The method of network pharmacology was employed to obtain the active components, potential core targets, and signaling pathways regulated by the herb pair in inhibiting angiogenesis in the inflammatory microenvironment of colorectal cancer, on the basis of which the underlying mechanism was predicted. The zebrafish model of colorectal cancer was established, and the inflammatory microenvironment was modeled. The effects of different concentrations of the herb pair on the area, number, and length of intersegmental vessels(ISVs) of the zebrafish model were observed. Western blot and real-time quantitative PCR were employed to measure the protein and mRNA levels, respectively, of vascular endothelial growth factor A(VEGFA), vascular epidermal growth factor receptor 2(VEGFR2, also known as kdrl, Flk1), and vascular epidermal growth factor receptor 3(VEGFR3, also known as Flt4). A total of 18 active components and 488 potential targets of Agrimoniae Herba-Coptidis Rhizoma were predicted, and 108 common targets were shared by the herb pair and the disease. According to the results of KEGG pathway enrichment analysis, the angiogenesis-related factors VEGFA, kdrl, and Flt4 in the VEGFA/VEGFR2 signaling pathway were selected for verification. The zebrafish experiment showed that compared with the blank group, the model group showed increased area, number, and length of ISVs in the inflammatory microenvironment. Compared with the model group, the herb pair decreased the area, number, and length of ISVs in a concentration-dependent manner. Compared with the blank group, the model group showed up-regulated protein and mRNA levels of VEGFA, kdrl, and Flt4 in the inflammatory microenvironment. Compared with the model group, the herb pair down-regulated the protein and mRNA levels of VEGFA, kdrl, and Flt4 in a concentration-dependent manner. The results indicated that in the colorectal cancer inflammatory microenvironment, the herb pair Agrimoniae Herba-Coptidis Rhizoma could inhibit angiogenesis via multiple components, targets, and pathways. The anti-angiogenesis effect might be related to the down-regulation of the expression levels of angiogenesis-related factors VEGFA, kdrl, and Flt4 in the VEGFA/VEGFR2 signaling pathway.

To investigate the clinical effect of electroacupuncture (EA) in preventing chemotherapy-induced peripheral neuropathy (CIPN).

Pembrolizumab (PEM) has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer (NSCLC), but clinical trials were based on cohorts of patients selected on specific criteria, and whether the findings are consistent with real-world patients is debatable. The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of oxaliplatin in colorectal cancer patients that may impact both physical and mental well-being significantly. When Western medical care alone is unable to satisfy patient needs, integrative care combining traditional Chinese and Western medicine approaches is an alternative option. This article shares the integrative care experience of a post-operative rectal cancer patient who suffered from chemotherapy-induced peripheral neuropathy. An intervention that followed a holistic assessment approach in traditional Chinese medicine (TCM; i.e., observation, auscultation, inquiry, and pulse feeling) combined with listening and communication was conducted between April 11th and May 27th, 2022. The patient's health problems were identified as chronic pain syndrome, sleep disturbances, and death anxiety. During the caring process, evidence-based practices were applied, the scientific literature was systematically reviewed using an evidence-based approach, and an integrative care plan was developed in collaboration with the medical team. Exercise, acupuncture, aromatherapy massage, music, and auricular acupressure therapies were administered to reduce the severity of the patient's health problems. It is hoped that this experience combining evidence-based knowledge with integrative care offers a reference for providing alternative patient care in a broad range of clinical settings.

Objectives: To explore the risk factors of major adverse cardiovascular events (MACEs) in immune checkpoint inhibitor (ICI) related myocarditis and establish a predictive model. Methods: This was a retrospective case-control study. Tumor patients diagnosed with ICI related myocarditis in the First Affiliated Hospital of Guangzhou Medical University from May 2019 to August 2023 were selected and divided into non-MACE group and MACE group based on whether MACE occurred. Clinical and imaging data of the two groups were collected. Univariate and multivariate logistic regression models were used to analyze the risk factors for MACE in patients with ICI related myocarditis. According to the results of multivariate logistic regression analysis, R 4.1.0 software was used to construct the MACE risk prediction model for these patients and draw a nomogram. The receiver operating characteristic curve was used to evaluate the prediction ability of the prediction model. Results: A total of 35 patients with ICI related myocarditis, aged (63.9±8.2) years, were included, including 28 males (80%). There were 18 patients in the non-MACE group and 17 patients in the MACE group. Multivariate logistic regression analysis showed that elevated neutrophil to lymphocyte ratio (OR=1.115, 95%CI 1.007-1.235, P=0.036) and ST-T segment changes (OR=24.942, 95%CI 1.239-502.194, P=0.036) were risk factors for MACE in patients with ICI related myocarditis. The receiver operating characteristic curve indicated that the area under the curve of the prediction model was 0.967 (95%CI 0.916-1.000, P<0.001), with a sensitivity of 88.2% and specificity of 100%, demonstrating good predictive ability. Conclusion: Elevated neutrophil to lymphocyte ratio and ST-T segment change are independent risk factors for MACE in patients with ICI related myocarditis. Risk prediction model based on the above two indicators can assist in the early identification and individualized intervention of ICI related myocarditis patients.

To investigate the clinical efficacy of heat-sensitive moxibustion combined with intrapleural perfusion of cisplatin in comparison with simple intrapleural perfusion of cisplatin on malignant pleural effusion (MPE).

The malignant tumor that has the highest global morbidity and death rate is lung cancer, which primarily affects the elderly. The therapy landscape for non-small cell lung cancer (NSCLC) has transformed with the introduction of immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the safety and efficacy of immune monotherapy and immunotheray combined with chemotherapy in patients with advanced NSCLC aged 75 years and above.

RS4;11 cell line was used to establish BCL-2 inhibitor-resistant cell lines of B-cell acute lymphoblastic leukemia (B-ALL) and explore the possible mechanisms of drug resistance.

Hazardous drugs represented by antineoplastic drugs have clear health hazards to occupational exposed populations, and this issue has received widespread attention all over the world in recent years. This article reviewed the laws, regulations, guidelines, and industry guidance documents for the prevention and control of occupational exposure to hazardous drugs issued by relevant departments and associations in the United States. It could provide a reference basis for the development of occupational environmental health standards and protection guidelines, with the aim of reducing the risk of occupational exposure to hazardous drugs and promoting the healthy development of healthcare services in China.

In order to obtain more effective cell culture parameters of Taxus anticancer plants, we optimized the callus induction and subculture conditions of the explants (stem segments with buds) of the anticancer medicinal plant Taxus media by using the plant tissue culture technology and orthogonal test. Furthermore, we studied the method to inhibit browning in the culture. The results indicated that the optimal conditions for inducing callus was culture in the medium composed of B5+0.25 mg/L 2, 4-D+1.5 mg/L NAA+0.5 mg/L KT in the dark, which showed short induction time and a high induction rate (86.7%). The formula of the optimal medium for subculture was B5+0.5 mg/L 2, 4-D+2.0 mg/L NAA+1.5 mg/L KT.The proliferation multiple of callus cultured by subculture on the 10th day of callus growth was the highest. Activated carbon inhibited the browning in callus subculture, with the optimal inhibitory concentration of 0.8 g/L. The results of this study lay a foundation for the production of taxol by suspension culture of T. media cells.

Microbial resources are diverse and abundant, serving as a crucial source for the discovery of bioactive substances. However, as the research on microbial secondary metabolites deepens, discovering new microorganisms and novel bioactive secondary metabolites from conventional environments is becoming increasingly challenging. The microorganisms inhabiting extreme environments have unique physiological characteristics and can develop distinctive metabolic pathways, holding immense potential for producing chemically diverse and novel bioactive secondary metabolites. This article comprehensively overviews the recent advancements in the isolation strategies of microorganisms from extreme environments and the research progress in their bioactive substances, including antimicrobial, anticancer, and antioxidant compounds. This review aims to serve as a reference for the development and utilization and the related studies of the microbial resources in extreme environments.

Objective: To observe the electrocardiogram (ECG) changes of programmed death receptor 1 (PD-1)/programmed death receptor-ligand 1 (PD-L1) immune checkpoint inhibitors before and after immunotherapy of patients during clinical antitumor process, and to explore the occurrence and influencing factors of cardiotoxicity of immune checkpoint inhibitors. Methods: A total of 93 patients with locally advanced or metastatic solid tumors confirmed by pathological diagnosis in Cancer Hospital of Chinese Academy of Medical Sciences from October 1, 2019 to September 30, 2020 were selected and treated with PD-1/PD-L1 inhibitor monotherapy. Groups were divided according to immunotherapy regimen: Group A (drug code: 609A), 16 patients were given 1 mg/kg of the drug for 21 days; Group B (drug code: HX008), 23 patients were treated with 200mg for 21 days; Group C (drug code: GB226), 28 patients were treated with 3mg/kg for 14 days; Group D (drug code: LP002), 26 patients were treated with 900mg for 14 days. The patients were monitored and followed up for 10 cycles. The ECG results of each group were recorded, and the correlation between ECG abnormality and cardiotoxicity was analyzed. Results: A total of 75 patients showed abnormal ECG that met the diagnostic criteria. There was no significant difference in abnormal ECG rate after immunotherapy in group A (P＞0.05), while the incidence of adverse cardiac events increased after immunotherapy in group B (P＜0.05), and the abnormal ECG rate increased significantly after chemotherapy in group C and group D. There was statistical difference before and after immunotherapy (P＜0.001). The number of abnormal cases in group A (8 cases, 50.0%, 8/16) was significantly lower than that of group B (20 cases, 87.0%, 20/23). The number of abnormal cases in group C and group D was 24 (85.7%) and 23 (88.4%), respectively, without statistical difference (P＞0.05), but their abnormal rates of ECG were higher than that in group A. The incidence of electrical adverse events in immunotherapy center of patients with underlying diseases was 1.93 times higher than that of patients without underlying diseases. The incidence of central electrical adverse events during immunotherapy in group B, C and D was 6.667, 6.000 and 7.667 times higher than that in group A, respectively. Conclusions: The high sensitivity of early ECG changes induced by immune checkpoint inhibitors enables early prediction of related cardiotoxicity. The presence or absence of comorbid underlying disease and drug dosage are correlated with the occurrence of adverse cardiac events, and these early changes provide a evidence for clinical treatment and prevention.