Epigallocatechin-3-gallate (EGCG), the predominant bioactive compound in green tea, has shown promise in lung cancer treatment; however, its molecular targets and antitumor mechanisms remain unclear. In this study, the therapeutic potential of EGCG against non-small cell lung (NSCLC) was evaluated, core targets were prioritized via network pharmacology, and molecular docking were employed to decipher the potential mechanism of action. Using bioinformatics, molecular docking, and functional enrichment analyses, 224 NSCLC-related targets were identified, with TP53, STAT3, AKT1, IL6, HSP90AA1, and JUN emerging as central hubs. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses revealed oxidative stress regulation and the PI3K/Akt pathway as critical mechanisms. Molecular docking confirmed strong binding affinities between EGCG and hub targets. These findings highlight EGCG as a multi-target agent against NSCLC via PI3K/Akt modulation, redox homeostasis restoration, and inflammation suppression, offering novel insights for phytochemical-based NSCLC therapy.

Lung cancer is a disease of global concern, and immunotherapy has brought lung cancer therapy to a new era. Besides promising effects in the clinical use of immune checkpoint inhibitors, immune-related adverse events (irAEs) and low response rates are problems unsolved. Natural products and traditional medicine with an immune-modulating nature have the property to influence immune checkpoint expression and can improve immunotherapy’s effect with relatively low toxicity. This review summarizes currently approved immunotherapy and the current mechanisms known to regulate immune checkpoint expression in lung cancer. It lists natural products and traditional medicine capable of influencing immune checkpoints or synergizing with immunotherapy in lung cancer, exploring both their effects and underlying mechanisms. Future research on immune checkpoint modulation and immunotherapy combination applying natural products and traditional medicine will be based on a deeper understanding of their mechanisms regulating immune checkpoints. Continued exploration of natural products and traditional medicine holds the potential to enhance the efficacy and reduce the adverse reactions of immunotherapy.

Background Breast cancer (BC) is the most frequent malignancy in the world. Chemotherapy (CT) is a common treatment for BC but is accompanied by toxicity and side effects. Shenqi Fuzheng Injection (SFI) is an adjuvant therapy with promising results in improving efficacy and reducing toxicity in clinical studies. This overview of systematic reviews and meta-analysis (SRs/MAs) aimed to summarize the benefits and evaluate the quality of evidence supporting SFI adjuvant as CT for BC. Methods A systematic search for SRs/MAs of randomized controlled trials (RCTs) on SFI treatment for BC was performed by searching PubMed, Web of Science, EMbase, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases from inception to October 1, 2022. The quality of SRs/MAs was evaluated using AMSTAR-2, PRISMA 2020, ROBIS, and GRADE by two reviewers. The corrected covered area (CCA) was used to quantify the degree of duplication of the original SRs/MAs. Finally, quantitative analysis of RCTs was conducted using RevMan 5.4 software. This study was registered with PROSPERO, CRD42022377290. Results Six SRs/MAs including 61 RCTs with 5593 patients were included in this study. Studies were published between 2015 and 2019, the original RCTs ranged from 7–49, with sample sizes ranging from 336–1989. The quantitative meta-analysis found that adjuvant CT of SFI improved the clinical response rate (RR=1.37, 95% CI=1.28, 1.46; P <0.00001) and the KPS score (RR=1.66, 95% CI 1.54, 1.79, P <0.00001) of patients with BC. In terms of immune function, CD3+ (SMD=1.51, 95% CI 0.91, 2.10; P <0.00001), CD4+ (SMD=1.87, 95% CI 1.18, 2.56; P <0.00001), CD4+/CD8+ (SMD=0.86, 95% CI 0.48, 1.23; P <0.00001), and NK cell levels (SMD=0.94, 95% CI 0.63, 1.24; P <0.00001) in the adjuvant CT group SFI were better than those with CT alone. Adverse reactions following SFI adjuvant CT showed reduced incidence of leukopenia (RR=0.53, 95% CI 0.46, 0.62; P <0.00001) and gastrointestinal reactions (RR=0.48, 95% CI 0.39, 0.58; P <0.00001). However, the GRADE results showed ‘very low’ to ‘moderate’ evidence for the 42 outcomes, without high-quality evidence supporting them, limited mainly by deficiencies in the design of RCTs (42/42, 100.00%), inconsistency (19/42, 45.24%), publication bias (41/42, 97.62%), and inaccuracy (3/42, 7.14%). The unsatisfactory results of AMSTAR-2, PRISMA 2020, and ROBIS were limited to lack of registration of study protocols, explanation of inclusion basis of RCTs, description of funding sources for the included studies, incomplete search strategy and screening process, addressing heterogeneity and sensitivity, and reporting potential conflicts of interest. Conclusion Adjuvant CT with SFI for BC had better benefits and a lower risk of adverse events. The methodology and quality of the evidence are generally low, highlighting a need of greater attention during study implementation. More objective and high-quality studies are needed to verify the efficacy of adjuvant CT with SFI in clinical decision-making for BC.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia, and 90% of APL patients carry positive fusion gene of the promyelocytic leukemia protein (PML)- retinoic acid receptor α (RARα), which drives the development of APL. All-trans retinoic acid and arsenic trioxide is able to cure 90% of APL patients by targeting PML-RARα. However, there are still 5%-10% of patients who will relapse due to drug resistance. Compound realgar-indigo naturalis formula (RIF) was developed based on the characteristics of APL pathogenesis. It contains four Chinese herbs: realgar, natural indigo, danshen root and heterophylly falsestarwort root. Clinical studies have confirmed that RIF has a certain efficacy on APL, which shown non-inferiority compared with arsenic trioxide. In addition, RIF combined with all-trans retinoic acid has become the first-line treatment regimen in APL guidelines in China. This study further clarified the efficacy of RIF on arsenic-resistant APL, explored the mechanism, and laid the foundation for further improving the efficacy of APL. O bjective: To investigate the mechanism of different combinations of the compound of RIF in reversing arsenic resistance in APL. M ethods: The arsenic-resistant cell line HL60-PML A216V-RARα, which could stably express PML A216V-RARα, was established by lentiviral transfection. Among compounds of RIF, the active compound of realgar is tetra-arsenic tetra-sulfide (As 4S 4, A), for natural indigo is indirubin (I), for danshen root is tanshinone IIa (T), and the for heterophylly falsestarwort root is total saponins of Radix Pseudostellariae (S). The four compounds were applied on the HL60-PML A216V-RARα cell line. Cell viability was detected by CCK-8 method. Hoechst staining was used to observe cell morphology, Annexin V/PI double staining was applied to detect cell apoptosis, JC-1 detection was used to detect mitochondrial membrane potential, flow cytometry was used to detect CD33 expression to evaluate cell differentiation, and Western blotting was used to observe the changes in the levels of PML A216V-RARα, apoptosis-related factors, PI3K/AKT/mTOR and autophagy in the control, A, ITS and AITS groups. The PI3K inhibitor LY294002 and the autophagy inhibitor Baf A1 were combined and applied to observe the changes in the levels of PML A216V-RARα, mTOR and p62 after blocking the PI3K or autophagy pathway. Results: The arsenic-resistant cell line HL60-PML A216V-RARα was successfully established. Compared with the control group, A, ITS and AITS groups all inhibited the growth of HL60-PML A216V-RARα cells in a time-dependent manner ( P < 0.0001). The IC50 value of AITS was significantly lower than the other groups ( P < 0.0001), and AITS group exhibited the strongest inhibitory effect, followed by ITS and A. Hoechst staining and JC-1 detection both showed that AITS had the strongest effect in inducing apoptosis. Annxin V/PI detection showed that the apoptosis rate of the control group was 10.04%, 15.19% for A group, 12.46% for ITS group, and 28.05% for AITS group. The differences between the groups were statistically significant ( P < 0.0001). Detection of CD33 expression showed: control group (79.72%), ITS group (79.19%), A group (28.60%), AITS group (24.46%), and there were significant differences between groups ( P < 0.001 or P < 0.0001). AITS could reduce PML A216V-RARα protein, caspase3, Bcl-2 levels more than ITS and A ( P < 0.05 or P < 0.0001), and ITS was better than AITS and A in increasing cleaved PARP-1 levels ( P < 0.0001). AITS decreased the levels of PI3K, mTOR, P-mTOR, AKT, p-AKT and p62 and increased the level of LC3B ( P < 0.001 or P < 0.0001). Electron microscopic detection of autophagy showed that AITS had the highest level of autophagy, AITS combined with LY294002 increased the level of p62 and decreased the level of mTOR ( P < 0.0001) compared to the AITS group; while when AITS was combined with Baf A1, the level of p62 increased ( P < 0.0001) and the level of mTOR also increased ( P < 0.001). Autophagy could induced by serum starvation. As the concentration of fetal bovine serum decreased, the effects of degrading PML A216V-RARα and p62, and LC3B level increasing were stronger. C onclusion: Tanshinone IIa, indirubin and total saponins of Radix Pseudostellariae could enhance the effect of tetra-arsenic tetra-sulfide down-regulating PML A216V-RARα, and the mechanism was suggested to be related to inhibiting mTOR pathway to activate autophagy.

PURPOSE:Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the first-line therapy for patients with lung adenocarcinoma (LUAD) harboring activating EGFR mutations. However, the emergence of drug resistance to EGFR-TKIs remains a critical obstacle for successful treatment and is associated with poor patient outcomes. The overarching objective of this study is to apply bioinformatics tools to gain insights into the mechanisms underlying resistance to EGFR-TKIs and develop a robust predictive model. METHODS:The genes associated with gefitinib resistance in the LUAD cell Gene Expression Omnibus (GEO) database were identified using gene chip expression data. Functional enrichment analysis, gene set enrichment analysis (GSEA), and immune infiltration analysis were performed to comprehensively explore the mechanism of gefitinib resistance. Furthermore, a GRRG_score was constructed by integrating genes related to LUAD prognosis from The Cancer Genome Atlas (TCGA) database with the screened Gefitinib Resistant Related differentially expressed genes (GRRDEGs) using the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses. Furthermore, we conducted an in-depth analysis of the tumor microenvironment (TME) features and their association with immune infiltration between different GRRG_score groups. A prognostic model for LUAD was developed based on the GRRG_score and validated. The HPA database was used to validate protein expression. The CTR-DB database was utilized to validate the results of drug therapy prediction based on the relevant genes. RESULTS:A total of 110 differentially expression genes were identified. Pathway enrichment analysis of DEGs showed that the differentially expressed genes were mainly enriched in Mucin type O-glycan biosynthesis, Cytokine-cytokine receptor interaction, Sphingolipid metabolism. Gene set enrichment analysis showed that biological processes strongly correlated with gefitinib resistance were cell proliferation and immune-related pathways, EPITHELIAL_MESENCHYMAL_TRANSITION, APICAL_SURFACE, and APICAL_JUNCTION were highly expressed in the drug-resistant group; KRAS_SIGNALING_DN, HYPOXIA, and HEDGEHOG_SIGNALING were highly expressed in the drug-resistant group. The GRRG_score was constructed based on the expression levels of 13 genes, including HSPA2, ATP8B3, SPOCK1, EIF6, NUP62CL, BCAR3, PCSK9, NT5E, FLNC, KRT8, FSCN1, ANGPTL4, and ID1. We further screened and validated two key genes, namely, NUP62CL and KRT8, which exhibited predictive value for both prognosis and drug resistance. CONCLUSIONS:Our study identified several novel GRRDEGs and provided insight into the underlying mechanisms of gefitinib resistance in LUAD. Our results have implications for developing more effective treatment strategies and prognostic models for LUAD patients.

Objective:To evaluate the effectiveness and safety of seven oral Chinese patent medicines(CPMs)as adjuvant therapy for cancer-related anemia(CRA)by network meta-analysis(NMA).Methods:A literature search to obtain randomized controlled trials(RCTs)of seven oral CPMs in the adjuvant treatment of CRA was conducted in multiple databases from the inception to April 2022.The RevMan5.3 and R 4.1.1 software were used for NMA.Results:We ultimately included 29 RCTs with 2140 patients.Traditional meta-analysis showed that Fufang E'jiao syrup(FFEJS),Shengxuebao mixture(SXBM),Shengxuening tablets(SXNT),Jianpi Shengxue granules(JPSXG),and Yixuesheng capsule(YXSC)combined with basic Western treatment(BWT)could improve the hemoglobin(HGB)level.JPSXG combined with BWTcould improve the red blood cell(RBC).FFEJS combined with BWT improved the Karnofsky performance status(KPS).NMA showed that FFEJS,JPSXG,SXBM,and SXNT plus BWT improved HGB better than Shengxue tablets(SXT)plus BWT,with top three ranking results being JPSXG plus BWT＞SXNT plus BWT＞FFEJS plus BWT.FFEJS plus BWT,JPSXG plus BWT,SXBM plus BWT,SXNT plus BWT,and SXT plus BWT improved RBC better than BWT,with top three ranking results being SXNT plus BWT＞JPSXG plus BWT＞FFEJS plus BWT.In terms of the KPS score,compared with SXT plus BWT,FFEJS,JPSXG,SXBM,SXNT,and Yizhong Shengxue capsule(YZSXC)plus BWT had higher KPS,with top three ranking results being SXBM plus BWT＞JPSXG plus BWT＞FFEJS plus BWT.Conclusions:Our NMA demonstrated that seven oral CPMs used as adjuvant treatment of CRA had a definite clinical effect.JPSXG not only increases the levels of HGB and RBC to enhance the clinical effect but also improves patients'quality of life.More accurate conclusions need to be verified by more high-quality RCTs.

To the editor,Lu et al raise excellent points regarding the Hepa1-6 model of HCC. Our study1 characterized the immune microenvironment of multiple preclinical models of HCC and showed that the Hepa1-6 model in C57BL/6J mice elicits a brisk immune infiltrate that is not representative of human HCC. This may be related to a minor major histocompatibility complex haplotype difference with the C57BL/6J mouse (H2b for C57BL/6 and H2bc for Hepa1-6), resulting in an alloreactive response. We conclude that the Hepa1-6 model should not be used for testing the effects of immunotherapy-based strategies for HCC. Lu et al expand on the limitations of the Hepa 1–6 model, proposing that the variability of this model's in vivo growth should preclude its use, even for nonimmunotherapy studies. We agree with the points raised by their letter. As discussed in their letter, we observed highly variable levels of tumor growth in the subcutaneous model of Hepa1-6, including complete regressions of some tumors without any intervention. This was observed over multiple independent experiments in our group in addition to the experiments included in our manuscript. While the Hepa1-6 model is currently among the most widely used for HCC research, we agree with Lu et al that given its highly variable tumor growth, it is a poor choice for in vivo drug discovery or testing. Moreover, there is a rapidly growing appreciation that even therapies originally thought to be nonimmunotherapeutic in mechanism in fact leverage the immune system to exert the observed antitumor responses. Given the association of the immune microenvironment with sensitivity or resistance to various treatment modalities including radiotherapy, cytotoxic chemotherapy, and targeted therapies,2–5 we seek to use models that most closely resemble human disease. We hope that our work can guide the design of future studies in HCC for the benefit of the patients suffering from this disease.

Ethnopharmacological relevanceIn China, the Chinese patent drug Realgar-Indigo naturalis Formula (RIF) is utilized for the therapy of acute promyelocytic leukemia (APL). Comprising four traditional Chinese herb—Realgar, Indigo naturalis, Salvia miltiorrhiza, and Pseudostellaria heterophylla—it notably includes tetra-arsenic tetra-sulfide, indirubin, tanshinone IIa, and total saponins of Radix Pseudostellariae as its primary active components. Due to its arsenic content, RIF distinctly contributes to the therapy for APL. However, the challenge of arsenic resistance in APL patients complicates the clinical use of arsenic agents. Interestingly, RIF demonstrates a high remission rate in APL patients, suggesting that its efficacy is not significantly compromised by arsenic resistance. Yet, the current state of research on RIF's ability to reverse arsenic resistance remains unclear.Aim of the studyTo investigate the mechanism of different combinations of the compound of RIF in reversing arsenic resistance in APL.Materials and methodsThe present study utilized the arsenic-resistant HL60-PMLA216V-RARα cell line to investigate the effects of various RIF compounds, namely tetra-arsenic tetra-sulfide (A), indirubin (I), tanshinone IIa (T), and total saponins of Radix Pseudostellariae (S). The assessment of cell viability, observation of cell morphology, and evaluation of cell apoptosis were performed. Furthermore, the mitochondrial membrane potential, changes in the levels of PMLA216V-RARα, apoptosis-related factors, and the PI3K/AKT/mTOR pathway were examined, along with autophagy in all experimental groups. Meanwhile, we observed the changes about autophagy after blocking the PI3K or mTOR pathway.ResultsTanshinone IIa, indirubin and total saponins of Radix Pseudostellariae could enhance the effect of tetra-arsenic tetra-sulfide down-regulating PMLA216V-RARα, and the mechanism was suggested to be related to inhibiting mTOR pathway to activate autophagy.ConclusionsWe illustrated that the synergistic effect of different compound combinations of RIF can regulate autophagy through the mTOR pathway, enhance cell apoptosis, and degrade arsenic-resistant PMLA216V-RARα.

中医药抗肿瘤现代化是中医肿瘤学发展的必然趋势.YIV906源于中医传统处方黄芩汤,采用标准化生产工艺,保证了黄芩汤质量的一致性,起初被命名为PHY906,后更名为YIV906.研究探寻YIV906处方渊源,明确YIV906与传统黄芩汤的联系及不同之处,以YIV906的研究思路为导向,从基础研究、临床研究的设计和评价体系,以及中药质量一致性等方面,探讨中医药抗肿瘤现代化研究策略,为今后中医药现代化抗肿瘤研究提供思路.

In order to analyze the early death rate of APL and its associated factors, we selected 3212 APL patients from 1986 to 2015 in the SEER database, of which 683 (21.3%) patients were noted for early death. we found that the early death rate in APL has decreased over the past few years, and older age, lower socioeconomic status were major factors affecting early death. These findings could give insights for clinicians to elaborately assess the epidemiology and risk factors of early death in APL.Background: Early death is a major factor of treatment failure in acute promyelocytic leukemia (APL), however, the recent trends in the incidence of early death based on the population-level are not clear. Hence, this study is aimed at describing the incidence, recent trends, causes and character istics of ear ly death in APL based on the real world.Materials and Methods: APL patients diagnosed from 1986 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) dataset were enrolled, and categorized based on gender, age, year of diagnosis, race, marital status, resident county and socioeconomic status (SES). The risk factors for all-cause and acute myelocytic leukemia (AML) specific early death were determined by univariate and multivariate logistic regression analyses, and stratified analysis was conducted by age.Results: Overall, 3212 APL patients were included in analysis between 1986 and 2015, of which a total of 683 (21.3%) patients were noted for early death. Significant differences were recognized for patient distribution by age, year of diagnosis, marital status, and SES. The early death rate of APL patients diagnosed during 2006-2015 was significantly lower than that of the early stage, but this trend was not evident in juvenile patients. At the same time, older age, and lower SES score were independent risk factors for early death in the multivariate analysis. Conclusion: We established that the early death trend in APL has decreased over the past few years, but the early death rate remains high, especially in older patients and those with lower SES.

茶多酚是茶叶的主要活性物质之一,表没食子儿茶素没食子酸酯(EGCG)则是茶多酚发挥生物作用的主要活性成分.二者作为免疫调节剂可用于肿瘤的治疗.本文从提高免疫效应、改善免疫逃逸两个方面综述茶多酚及EGCG的抗肿瘤作用机制.结果发现,茶多酚及EGCG不仅可以通过活化免疫细胞与促进细胞因子分泌来提高抗肿瘤免疫效应,还可通过调节免疫抑制细胞、调控免疫检查点、调节细胞因子、抑制免疫调节酶与Janus激酶/信号转导和转录激活子(JAK/STAT)通路来改善肿瘤免疫逃逸,在肿瘤免疫治疗方面具有较大潜力.

FAM107A may have a dual role in regulating the biological functions of tumors; however, its role in prostate adenocarcinoma (PRAD) remains unknown. We analyzed FAM107A expression by employing databases to clarify its potential prognostic value for PRAD, as well as its role in the pathogenesis of PRAD. We observed that the FAM107A expression level is decreased in PRAD, and the reduced expression is considerably associated with poor overall survival and progression-free survival (PFS). To explore the mechanism of FAN107A in PRAD, we performed an immune cell infiltration analysis and a gene set enrichment analysis. The results showed that FAM107A expression is positively related to mast cells and natural killer cells. The Wnt signaling pathway, the MAPK signaling pathway, and the immune responses are differentially enriched in the FAM107A high-expression phenotype. The FAM107A low-expression phenotype is linked to apoptosis-induced DNA fragmentation and DNA methylation in PRAD. To assess the relationship between the clinical features and the FAM107A expression, we performed a logistic regression analysis and observed that a decreased FAM107A expression is associated with poor prognostic features, including the T stage, the N stage, the Gleason score, residual tumors, and the TP53 status. Our multivariate Cox regression results showed that the Gleason score, the primary therapy outcome, and the FAM107A expression are independent prognostic factors in PFS. In summary, we consider FAM107A an independent risk factor for PFS in PRAD. Moreover, several pathways may reveal the role of FAM107A in triggering carcinogenesis. These discoveries provide novel perspectives for future research to elucidate the pathogenic mechanism underlying PRAD.

Objective:To investigate the clinical significance of coagulation function related indicators in the prognosis of non-small cell lung cancer.Methods:The clinical data of 248 patients with non-small cell lung cancer from June 2014 to December 2017 in the Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to determine the best cutoff values of prognostic indicators,the Cox regression model was used for multivariate analysis, and the Kaplan-Meier method was used for survival analysis.Results:ROC curve analysis showed that the best cutoff values for D-dimer (D-D), fibrinogen (FIB) and prothrombin time (PT)were 0.18 mg/L, 4.25 g/L and 12.0 s, respectively. Cox multivariate regression analysis showed that increased expression of D-D ( HR=1.197, 95% CI 1.100-1.303), PT ( HR=1.111, 95% CI 1.049-1.176) and FIB ( HR=1.510, 95% CI 1.276-1.788) were risk factors for the prognosis of non-small cell lung cancer ( P<0.001). Kaplan-Meier survival analysis results showed that the overall survival in the high expression group of D-D, FIB and PT was shorter than in of the low expression group ( P<0.001). Conclusion:D-D, PT and FIB are independent factors affecting the prognosis of non-small cell lung cancer.

目的:观察固本消瘤胶囊加减方及其联合吉非替尼对非小细胞肺癌PC9及吉非替尼耐药株PC9GR细胞的增殖、迁移、凋亡及细胞周期的影响.方法:应用MTT法检测细胞增殖能力;细胞划痕实验检测细胞的迁移能力;流式细胞术观察细胞的凋亡和周期.结果:固本消瘤胶囊加减方与吉非替尼可呈浓度依赖性抑制PC9及PC9GR细胞的增殖,且联合用药后具有显著的增效作用(P＜0.05);两药均可减弱两种细胞的划痕修复能力,联合用药同样具有显著的增效作用(P＜0.05);两药均可显著增加细胞的凋亡率,且联合用药组细胞凋亡率显著高于两个单药组(P＜0.05),同时各组用药对两种细胞的G0/G1期均产生了不同程度的抑制,但联合用药的抑制作用弱于单用吉非替尼(P＜0.05).结论:固本消瘤胶囊加减方可以显著抑制PC9及PC9GR细胞的增殖、迁移,其作用机制与诱导细胞凋亡、阻滞细胞周期有关;同时该方与吉非替尼联合应用在抑制细胞增殖、迁移,诱导细胞凋亡方面具有明显的增效作用.

Although several epidemiological studies have investigated associations between poultry and fish consumption and pancreatic cancer (PC) risk, these findings have been inconsistent. The present study aimed to perform a meta-analysis to comprehensively evaluate these associations. We retrieved Eligible cohort studies and case-control studies published before February 2020 from the Medline, EMBASE, and Cochrane Library and applied a random or fixed effects model to calculate the pooled relative risk (RR) and the corresponding 95% confidence intervals (CI). Publication bias was detected using funnel plots, Begg's test, and Egger's test, and the study quality was evaluated using the Newcastle-Ottawa scale. We included 25 studies in the analyses. The pooled RR of PC for the highest vs. lowest poultry intake category was 1.14 (95% CI: 1.02-1.26) in cohort studies. There was no appreciable link between fish intake and PC risk (RR: 1.00, 95% CI: 0.93-1.07). Our results suggest that large amount of poultry intake may increase PC risk, while fish intake is unlikely to be linked to PC risk. These links require further investigation, particularly between poultry and PC.

OBJECTIVE:To systematically explore the pharmacological mechanism of Radix Paeoniae Rubra (RPR) against lung cancer (LC).METHODS:A network pharmacology approach, which involves active ingredients and target forecast, network construction, gene ontology and pathway enrichment, was employed in this research. In addition, the effect of Baicalein (BAI) in RPR on A549 cells was researched in vitro and in vivo.RESULTS:A total of 159 targets of the 29 active components in RPR were procured by pharmacokinetic parameters. The network analysis showed that β-sitosterol, baicalein, (+)-catechin, ellagic acid, stigmasterol, (2R, 3R)-4-methoxyl-distylin were the main ingredients and JUN, VEGFA, BCL2 were the hub targets of RPR in the treatment of LC. The functional enrichment analysis showed that RPR likely was useful to LC by regulating numerous pathways including Pathways in cancer, MAPK signaling pathway and so on. MTT results showed that 100μM, 200μM, 400μM of BAI had a time and dose-dependent inhibitory effect on A549 cells proliferation; Wound healing and transwell assays showed that 100μM, 200μM, 400μM of BAI could significantly restrain the migration and invasion of A549 cells; Flow cytometry assay results showed that 100μM, 200μM, 400μM of BAI could induce apoptosis of A549 cells. In vivo, BAI (50, 100 mg/kg) significantly inhibited tumor growth and promoted apoptosis of tumor cells compared with the control group.CONCLUSION:BAI in RPR may exert anti-tumor effects by inhibiting the proliferation, migration and invasion of LC cells, and inducing the apoptosis of LC cells.

Objective: We explored the clinical regularity and prognosis of lung carcinoma (LC) patients with hypercoagulability, which is often associated with the occurrence and development of tumors.Methods: This retrospective study analyzed 624 LC patients diagnosed from 2010-2017 in the Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, China.Kaplan-Meier analysis was used to estimate survival and the log-rank test was used to identify differences in survival between groups.The predictive power of a hypercoagulation model was tested using receiver operating characteristic (ROC) curve analysis.Univariate and multivariate Cox regression analyses were performed to explore independent factors associated with survival.A logistic regression model was used to explore factors related to hypercoagulability.The diagnostic power of relevant influencing factors on hypercoagulability was tested using ROC curve analysis.Results: Of 624 patients in the study, 161(25.8%)had hypercoagulability and 463 did not (normal group).The overall survival (OS) of the hypercoagulability group was significantly lower than the normal group (P < 0.0001).The ROC curve showed that the predictive power of the hypercoagulability model was better than that of a single coagulation indicator (P < 0.01).Both univariate and multivariate Cox regression analyses showed that hypercoagulability was an independent factor affecting the prognosis of LC (P<0.0001).The results of the logistic regression analysis showed that clinical stage (P < 0.05), cytokeratin 19 fragment (Cyfra211) (P < 0.05), and the platelet-to-lymphocyte ratio (PLR) (P < 0.05) were positively correlated with hypercoagulability.When combining clinical stage, Cyfra211, and the PLR to predict hypercoagulability, the area under the ROC curve was 0.797 (P < 0.01).Conclusions: In LC, hypercoagulability is an independent factor associated with poor OS and could be a prognostic factor.

Targeting EGFR, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), brings lights to the treatment of non-small cell lung cancer (NSCLC). Although T790M mutation responded as one of the main reasons of acquired resistance, still 15% of the resistance patients can't be explained by the known mechanisms. The purpose of this research was to identify some new mechanisms of gefitinib acquired resistance, and to predict small molecules drugs which may reverse drug resistance by integrated bioinformatics analysis. The GSE34228 data package containing the microarray data of acquired gefitinib-resistant cell line (PC9GR) and gefitinib-sensitive cell line (PC9) from the GEO database were downloaded, and gene co-expression networks by weighted gene co-expression network analysis (WGCNA) were constructed to identified key modules and key genes related to gefitinib resistance. Furthermore, the significantly differentially expressed genes (DEGs) between the two cell types were screened out, and a protein-protein interaction (PPI) network to obtain the key genes of DEGs was accordingly constructed. Through the above two methods, 4 hub genes, PI3, S100A8, AXL and PNPLA4 were mined as the most relevant to gefitinib resistance. Among them, PI3, S100A8 were down-regulated in PC9GR cell samples, while AXL, PNPLA4 were up-regulated. The gene set enrichment analysis (GSEA) for single gene showed that the four hub genes were mainly correlated with cell proliferation and cycle. Besides, small molecule drugs with the potential to overcome resistance, such as Emetine and cephaeline, were screened by CMap database. Consistent with this, in vitro experiments results have shown that emetine and cephaeline can increase the sensitivity of drug-resistant cells to gefitinib, and the mechanism may be related to the regulation of PI3 and S100A8. In conclusion, 4 hub genes were found to be related to the occurrence of gefitinib resistance in non-small cell lung cancer, and several small molecule drugs were screened out as potential therapeutic agents to overcome gefitinib resistance, which may lead a new way for the treatment of NSCLC of acquired resistance to gefitinib.

A potential relationship between poor prognosis and thrombocytosis has been suggested by previous studies in lung cancer, but the conclusions continued to be controversial. Here, we performed a meta-analysis to explore the prognostic impact of thrombocytosis in lung cancer. The Cochrane Library, EMBASE and PubMed databases were comprehensively and systematically retrieved from establishment to May 5, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were applied to evaluate overall effects. Heterogeneity was assessed using I(2)statistics and Cochran's Q test. Sensitivity and subgroup analyses were performed to analyze the sources of heterogeneity. Publication bias was examined using the Egger's test and pooled HR was regulated using the trim-and-fill approach when publication bias was observed. A total of 37 studies including 14,833 patients were enrolled in the meta-analysis. Thrombocytosis was significantly correlated to poor overall survival (HR 1.033; 95% CI 1.017-1.050), disease-free survival (HR 1.568; 95% CI 1.276-1.928), and progression-free survival (HR 1.653; 95% CI 1.069-2.556). Although publication bias was identified, rectification for this bias using the trim-and-fill approach did not change the combined HR substantially. In conclusion, this meta-analysis result suggested that thrombocytosis is a predictor of poor prognosis in lung cancer.

半枝莲和白花蛇舌草是癌症治疗当中常用的清热解毒中药,在中医临床遣方用药当中常相须配伍使用.近些年,陆续有中医药研究团队展开对此药对的研究,随着现代研究手段的进步,研究内容也从临床病案的总结观察逐步深入到基础实验机制的挖掘和探讨,在主治功效、剂型和成分、比例和用量、作用机制以及中医理论探讨等方面均有涉及.现将所报道的研究进行综述,旨在梳理半枝莲和白花蛇舌草药对研究现状,为更加深入的研究和探讨做铺垫.