Isoliquiritigenin (2’-4’-4-trihydroxychalcone, ISL), a flavonoid from the herbal medicine Glycyrrhiza uralensis Fisch, has promising antitumor effects. While ISL has demonstrated anti-cancer potential, its comprehensive molecular mechanism of action in lung cancer remains inadequately explored, particularly in the context of combination therapy with gemcitabine (Gem). This study conducted in vivo and in vitro experiments to investigate the anti-lung cancer effect of ISL (50 mg/kg/d), in combination with Gem (50 mg/kg/3d) (ISL + Gem) and elucidate the molecular mechanism of ISL (25 µM) combined with Gem (1 µM) (ISL + Gem) in inducing apoptosis and inhibiting proliferation of lung cancer cells. The results revealed that ISL + Gem exerted its antitumor effects by promoting apoptosis and inhibiting the proliferation of lung cancer cells as well as their ability to invade and metastasize. It was discovered that long non-coding RNA (lncRNA) -p21 was differentially lowly expressed in human non-small cell lung cancer (NSCLC) tissues. In vitro studies confirmed that combined ISL and Gem treatment increased lncRNA-p21 expression in NSCLC cell lines. Inhibitory effects of proliferation, invasion and migration as well as induction of apoptosis by ISL + Gem can be enhanced by the overexpression of lncRNA-p21 and eliminated by knock-down of lncRNA-p21. Luciferase assays revealed that lncRNA-p21 acts as a competing endogenous RNA (ceRNA) for miR-4534, which was significantly upregulated in NSCLC tissues compared to normal controls. Treatment with ISL, Gem, or their combination effectively suppressed miR-4534 expression in H460 cells. Further studies revealed that ISL + Gem, overexpression of lncRNA-p21 or silencing of miR-4534 inhibited the expression of CXC chemokine ligand-12 (CXCL12), as well as janus kinase 2 and signal transducer activator of transcription 3 (JAK2/STAT3) pathway-related proteins. In contrast, knock-down of lncRNA-p21 or overexpression of miR-4534 reversed the above effects of ISL + Gem. In conclusion, this study showed that ISL combined with Gem could effectively impede the progression of lung cancer partially through inactivating JAK2/STAT3 signaling pathway via lncRNA-p21/miRNA-4534 axis.

Programmed cell death (PCD) is a fundamental barrier to tumorigenesis, but cancer cells often evolve ways to evade single-mode death pathways. PANoptosis is a newly recognized form of PCD that integrates features of pyroptosis, apoptosis, and necroptosis. PANoptosomes organize this pathway and can induce cell death even when individual PCD modes are compromised. Evidence suggests that targeting PANoptosome-mediated PANoptosis may induce immunogenic cell death, alter the tumor microenvironment (TME), and enhance the efficacy of chemotherapy, radiotherapy, and immune checkpoint blockade (ICB). By leveraging multiple cell death routes, PANoptosis may also help overcome drug resistance and immune evasion. However, clinical translation faces challenges due to pathway redundancy, systemic inflammatory toxicity, and tumor heterogeneity. Following an overview of apoptosis, pyroptosis, necroptosis, and their crosstalk, this review explores the molecular basis of PANoptosis, the organization and regulation of PANoptosomes, and the related emerging opportunities and challenges in cancer treatment. While still under development, further investigation into PANoptosome assembly and therapies targeting this pathway may offer new strategies and improve patient outcomes.

Rationale: Immune checkpoint inhibitors, particularly programmed cell death protein 1 (PD-1) blockers, have transformed cancer therapy but can induce immune-related endocrine toxicities. Severe involvement of multiple endocrine axes, including dual pituitary dysfunction, is rare and challenging to diagnose due to nonspecific clinical features. Highlighting such cases can improve early recognition and management. Patient concerns: A 56-year-old man with esophageal cancer developed fatigue, polyuria, polydipsia, dizziness, and severe hyponatremia after treatment with tislelizumab, a PD-1 inhibitor. Diagnoses: Laboratory evaluation revealed new-onset autoimmune diabetes, hypothyroidism, and secondary adrenal insufficiency. The constellation of biochemical abnormalities and clinical features, in the absence of alternative etiologies, indicated immune-related hypophysitis and pancreatic islet injury. Two additional cases of severe, recurrent hyponatremia after PD-1 therapy were also reviewed. Interventions: The patient received targeted hormone replacement therapy, including glucocorticoids and levothyroxine, along with insulin for glycemic control. Outcomes: Symptoms improved significantly, and biochemical parameters normalized following treatment, demonstrating effective management of multi-glandular endocrine failure induced by PD-1 blockade. Lessons: PD-1 inhibitors can cause severe, concurrent dysfunction of multiple endocrine organs. Clinicians should maintain high vigilance, implement proactive screening for pituitary and metabolic abnormalities during and after immune checkpoint inhibitor therapy, and adopt a multidisciplinary approach to ensure timely diagnosis and treatment.

Background Non-invasive methods with universal prognostic guidance for detecting breast cancer (BC) survival biomarkers need to be further explored. Objective This study aimed to investigate C-C motif chemokine receptor type 5 (CCR5) prognosis value in BC and develop a radiomics model for noninvasive prediction of CCR5 expression in BC. Methods A total of 840 cases with genomic information were included and divided into CCR5 high- and low-expression groups for clinical characteristic differences exploration. Bioinformatics and survival analysis including Kaplan-Meier (KM) survival analysis, Cox regression, immunoinfiltration analysis, and tumor mutation load (TMB) were performed. For radiomics model development, 98 cases with dynamic contrast-enhancement magnetic resonance imaging (DCE-MRI) scans were used. Radiomics features extracted were using Pyradiomics and filtered by maximum-relevance minimum-redundancy (mRMR) and recursive feature elimination (REF) algorithms. Support vector machine (SVM) and logistic regression (LR) models were developed to predict CCR5 expression, with the radiomics score (Rad_score) representing the predicted probability of CCR5 expression. The models’ performance was compared using the Delong test, and the model with the superior area under the curve (AUC) values was selected to analyze the correlation between CCR5 expression, Rad_score, and immune genes. Results The CCR5 high-expression group exhibited better overall survival (OS) (p < 0.01). Six radiomics features were selected for model development. The AUCs of the SVM model predicting CCR5 were 0.753 and 0.748 in the training and validation sets, respectively, while the AUCs of the LR model were 0.763 and 0.762. Calibration curves and decision curve analysis (DCA) validated the models’ calibration and clinical utility. The SVM_Rad_score showed a strong association with immune-related genes. Conclusions The DCE-MRI radiomics model presents a novel, non-invasive tool for predicting CCR5 expression in BC and provides valuable insights to inform clinical decision-making.

Background: This research attempts to clarify whether there are any genetic similarities between sleep traits and hypothyroidism based on publicly accessible large-scale genomewide association studies. Methods: The methodology included colocalization analysis, crossphenotype association analysis, and linkage disequilibrium score regression analysis to find common genetic overlap. Through tissue function specificity and functional mapping, we were able to identify the shared genetic level. Genetic instrumental factors were used for causal inference in two-sample univariate and multivariable Mendelian randomization analyses. Results: A hereditary correlation between hypothyroidism and napping during the day and getting up in the morning (rg=-0.0982, P=0.0007; rg=-0.101, P=0.0001). MAGI3, and HLA-DRB1 BX296568.1 may be potential targets for shared treatments. Colocalization and tissue-specific analysis demonstrated that the common genes and SNPs were identified in the thyroid, lung, brain, and lymphatic tissues. Functional analysis emphasized the importance of these common genes in processes like as protein transport, inflammatory response, and MHC class II protein synthesis. Furthermore, an association has been established between hypothyroidism and sleep duration (IVW, OR 1.5208; 95% CI 1.1142-2.0758, P=0.0082) and getting up in the morning (IVW, OR 1.8375; 95%CI: 1.4502-2.3284, P=4.73E-07). Furthermore, the reverse MR analysis revealed no causal connection between aberrant sleep traits and hypothyroidism. The enduring impact of insomnia on hypothyroidism persists despite controlling for alcohol consumption and smoking habits. Conclusion: Certain genetic correlations between sleep traits and hypothyroidism have been emphasized. These findings may elucidate the origin of comorbidity and have implications for future clinical trials.

Objective : This study aimed to investigate the impact and mechanism of Shengyu Jiedu Tang(SYJDT) lyophilized powder on a cancer-induced muscular atrophy cell model by modulating the mitochondrial autophagy-NLRP3 inflammatory pathway. Methods : Mouse myoblasts C2C12 were exposed to the supernatant of Lewis lung carcinoma (LLC) to establish a carcinogen-induced muscular atrophy cell model. Various parameters including cell proliferation, migration, myotube atrophy, ROS levels, mitochondrial membrane potential, and expression of proteins in the mitochondrial autophagy-NLRP3 signaling pathway were assessed following treatment with different concentrations of Shengyu Jiedu Tang lyophilized powder. Results : The cancer-induced muscular atrophy cell model was successfully developed, demonstrating myotube atrophy, reduced myotube diameter, elevated TNF-α and IL-6 levels in the culture medium. Treatment with Shengyu Jiedu Tang lyophilized powder significantly suppressed cell proliferation and migration, ameliorated myotube atrophy, decreased ROS levels, enhanced mitochondrial membrane potential, upregulated mitochondrial autophagy-related proteins (LC3, Pink1, Parkin), downregulated P62 protein expression, inhibited NLRP3 inflammasome activation, and reduced inflammatory factor expression. Mitophagy inhibitors partially reversed the effects of the lyophilized powder, suggesting a close association with mitophagy. Conclusion : Shengyu Jiedu Tang lyophilized powder can attenuate cancer-induced muscular atrophy by stimulating mitochondrial autophagy, modulating mitochondrial function, suppressing NLRP3 inflammasome activation, and reducing inflammatory factor expression.

Non-small cell lung cancer(NSCLC) is the most common type of lung cancer worldwide, accounting for approximately 80%-85% of all lung cancer cases. Despite the clinical benefits of traditional treatments such as surgery, chemotherapy, and radiotherapy, challenges such as the high rate of postoperative recurrence and resistance of some patients to chemotherapy and targeted therapies limit their effectiveness, necessitating the exploration of more effective treatment options. In recent years, immunotherapy, especially immune checkpoint inhibitors(ICIs), has revolutionized NSCLC treatment and significantly improved the survival prognosis of some patients. However, the efficacy of immunotherapy is limited by tumor immune escape, drug resistance, and immune-related adverse events(irAEs), which have not been effectively addressed. Traditional Chinese medicine(TCM), as a traditional therapeutic approach, has shown unique advantages in NSCLC treatment, with studies indicating its ability to enhance immune responses, regulate immune checkpoints, and improve the tumor microenvironment(TME), thus boosting the efficacy of immunotherapy. Additionally, the multi-target and multi-pathway effects of TCM help mitigate the side effects of immunotherapy, further improving efficacy and safety. This review summarizes the latest research progress of TCM in NSCLC immunotherapy, focusing on the research results of TCM in enhancing the effect of immunotherapy by regulating immune cells, optimizing the immune microenvironment, and being applied with ICIs, etc. The latest research progress of TCM in alleviating irAEs is also elucidated. The aim is to provide theoretical support for the clinical application of TCM in the prevention and treatment of NSCLC and the research and development of new drugs and promote the optimization and development of combined immunotherapy and TCM treatment models.

Ethnopharmacological relevance The Xiaoai Jiedu recipe (XJR) is a traditional Chinese medicine formulation used in clinical settings to treat liver cancer. It has shown promising effectiveness by combining herbal and animal-derived ingredients, offering a new approach to cancer treatment. However, its mechanism of action is poorly understood. Aim of the study The molecular processes underlying the inhibitory effects of the XJR on hepatocellular cancer (HCC) were investigated. Materials and methods The primary chemical components of XJR and associated disease targets relevant to HCC were anticipated and compiled using a database. The potential targets and processes by which XJR influenced HCC were investigated using GO and KEGG enrichment analyses, as well as protein-protein interaction (PPI) networks. Transmission electron microscopy, laser confocal microscopy, and Western blotting were used to evaluate autophagy, while CCK-8 assays measured cell viability and Western blotting and flow cytometry evaluated apoptosis. In vivo assays were conducted employing an HCC xenograft mouse model. Results Network pharmacology analysis identified 456 intersecting targets between XJR and HCC. The top five active components are quercetin, cholesterol, jaceosidine, eupafolin, and oleanolic acid. The key targets include TP53, AKT1, IL6, EGFR, SRC, HSP90AA1, TNF, IL1B, MYC, and CASP3. Additionally, the autophagy pathway was found to be one of the main pathways through which XJR intervenes in HCC. The increased quantity of autophagosomes and autolysosomes, the overexpression of Beclin1 and LC3A/B-II proteins, and the downregulation of P62 all suggest that XJR stimulated autophagy in HCC cells. Functional tests employing pathway-specific activators and inhibitors and siRNA-based knockdown demonstrated that XJR promoted autophagy by blocking AKT/mTOR signaling. Furthermore, XJR reduced the viability of HCC cells and promoted apoptosis by upregulating apoptosis proteins. Autophagy inhibitors and Beclin1 silencing reversed these effects. Research conducted in vivo showed that XJR activated autophagy through the AKT/mTOR axis, thereby markedly reducing tumor growth and inducing tumor cell demise. Conclusions These studies show that XJR activates autophagy in both cellular and animal models to induce apoptosis and decrease HCC cell proliferation, as shown by network pharmacology and verification assays. Further, these findings provide experimental evidence that the anti-tumor activity of XJR involves autophagy stimulation.

Colorectal cancer (CRC) is characterized by an immunosuppressive and inflammatory microenvironment, thus responds poorly to therapy. Previous studies show that norcantharidin (NCTD), a demethylated cantharidin (CTD) derived from Mylabris, exerts high efficacy in treating various cancers. In this study we investigated the antitumor effects of NCTD against CRC and the underlying mechanisms. Subcutaneous CRC models were established in balb/c mice using mouse colorectal cancer cell line CT26 and in balb/c nude mice using human colorectal cancer cell line HCT116. The mice were administered NCTD (2 or 4 mg·kg−1·d−1, i.p.) for 14 days. We showed that NCTD dose-dependently reduced the tumor growth in both the CRC models. Furthermore, NCTD markedly increased M1 macrophage infiltration in tumor tissue in both the CRC models. NCTD-induced macrophage M1 polarization was confirmed by flow cytometry and qPCR assays in both THP-1 cell-derived and RAW264.7 macrophage models in vitro. We demonstrated that NCTD (20, 40 μM) dose-dependently increased CSF2 secretion from CRC cells and macrophages, and suppressed the JAK2/STAT3 signaling pathway in CRC cells. Concurrently, NCTD (10–40 μM) dose-dependently inhibited CRC cell proliferation, invasion and migration in vitro. In conclusion, this study provides new evidence for the effects of NCTD against CRC and elucidates its antitumor mechanisms through remodeling the inflammatory microenvironment via CSF2-mediated macrophage M1 polarization and inhibiting JAK2/STAT3 phosphorylation in CRC cells.

Objective:Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods:First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results:Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion:Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.

BACKGROUND:Type 2 diabetes-associated cognitive dysfunction (DCD) is a chronic complication of diabetes that has gained international attention. The medicinal compound Banxia Xiexin Decoction (BXXXD) from traditional Chinese medicine (TCM) has shown potential in improving insulin resistance, regulating endoplasmic reticulum stress (ERS), and inhibiting cell apoptosis through various pathways. However, the specific mechanism of action and medical value of BXXXD remain unclear. METHODS:We utilized TCMSP databases to screen the chemical constituents of BXXXD and identified DCD disease targets through relevant databases. By using Stitch and String databases, we imported the data into Cytoscape 3.8.0 software to construct a protein-protein interaction (PPI) network and subsequently identified core targets through network topology analysis. The core targets were subjected to Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The results were further validated through in vitro experiments. RESULTS:Network pharmacology analysis revealed the screening of 1490 DCD-related targets and 190 agents present in BXXXD. The topological analysis and enrichment analysis conducted using Cytoscape software identified 34 core targets. Additionally, GO and KEGG pathway analyses yielded 104 biological targets and 97 pathways, respectively. BXXXD exhibited its potential in treating DCD by controlling synaptic plasticity and conduction, suppressing apoptosis, reducing inflammation, and acting as an antioxidant. In a high glucose (HG) environment, the expression of JNK, Foxo3a, SIRT1, ATG7, Lamp2, and LC3 was downregulated. BXXXD intervention on HT22 cells potentially involved inhibiting excessive oxidative stress, promoting neuronal autophagy, and increasing the expression levels of JNK, SIRT1, Foxo3a, ATG7, Lamp2, and LC3. Furthermore, the neuroprotective effect of BXXXD was partially blocked by SP600125, while quercetin enhanced the favorable role of BXXXD in the HG environment. CONCLUSION:BXXXD exerts its effects on DCD through multiple components, targets, levels, and pathways. It modulates the JNK/SIRT1/Foxo3a signaling pathway to mitigate autophagy inhibition and apoptotic damage in HT22 cells induced by HG. These findings provide valuable perspectives and concepts for future clinical trials and fundamental research.

According to the theory of five movements and six climates, the innate constitution plays a crucial role in determining the underlyingpa thological mechanisms of diseases later in life. Previous studies have demonstrated a close association between the constitution, as defined by the theory of five movements and six climates, and the development of various types of tumors. Furt hermore,the tumorsubtype determined by the constitution has prognostic implications. This highlights the potential of utilizing the fivemovements and six climates theory to guide the implementation of precision medicine strategies in thefield of oncology. However, no resear ch has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precisi onmedicine strategies. The objective of this research is to uncover the biological characteristics of each constitution within a pancanc ercohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types. By doing so, we aimto c ontribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chi nesemedicine(TCM). In this study, we obtainedpan-cancer Bulk RNA-Seq data from UCSC Xena, GWAS cohort data from the UKBiobank, and cis-eQTLs data from eQ TLGen and GTEx V8. We employed machine learning methods to screen for hub genes associated with each constitution. Subsequently, we utilized informatics tools to explore the biological characteristics of each constitut iondefined by the theory of five movements and six bioclimates. Further, potential anti-tumor drugs suitable for patients with differen tconstitutional types were identified through mendelian randomization, molecular docking, and drug-like prediction techniques. Withinthe pan-cancer cohort, significant differences were observed among different constitutions in terms of progression-free interval, biological f unctions, immune cell abundance, tumor drug sensitivity, and immunotherapy response. These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies. Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicinetheories, offering a fresh perspective towards clinical cancer treatment. Through molecular docking and drug-like prediction, several po tential anti-tumor drugs such as 17-beta-estradiol, serotonin, trans-resveratrol, and linoleic acid were identified. Overall, the util izationof multi-omics approaches pro vides a powerful tool to unravel the scientific foundations of TCM theories. The elucidation of themu lti-omics features associated witheach constitution in tumors serves as the basis for applying the five movements and six climates theoryto tumor molecular classification and the development of precision medicine strategies.

PURPOSE:We aimed to investigate the pharmacological effects and mechanisms of the Aitongping formula for treating cancer pain.METHODS:We enrolled 60 cancer patients with Numeric Rating Scale above 4 and grouped them randomly as a Control group (N = 30) and a Patch group (N = 30). We also established bone cancer mice models via tumor implantation. And the animal groups were established as a Sham group, a tumor cell implantation (TCI) group, a TCI + Patch group, and a Patch group.RESULTS:After the validation of successful tumor implantation, we identified candidate miRNAs and genes that were dysregulated in TCI mice and compared their expressions between different mice groups. We also observed the effect of Aitongping patch in vitro in mice primary microglia. The time to disease progression and cancer stability were prolonged by Aitongping patch in cancer patients. And the daily morphine dose was lower, and patients' quality of life was improved in the Patch group. Moreover, Aitongping patch alleviated cancer pain and inhibited microglia activation after the successful implantation of bone tumor in TCI mice. We also observed the dysregulation of miR-150-5p and chemokine CXC motif ligand 12 (CXCL12) mRNA in TCI mice. And CXCL12 was found to be targeted by miR-150-5p. Aitongping patch was found to upregulate miR-150-5p and downregulate CXCL12 in vivo and in vitro.CONCLUSION:Aitongping patch could alleviate cancer pain via suppressing microglia activation, and the downregulation of miR-150-5p, as well as the upregulation of CXCL12 mRNA and protein, induced by tumor implantation or lipopolysaccharide stimulation, was restored by Aitongping treatment.

Abstract Objective Blood serves as a powerful tool for monitoring the intricate landscape of cancer development. Previous studies have emerged, suggesting that hematologic indicators hold promise in predicting the onset of malignancy. This present investigation aims to delve into the underlying causal connections between blood-related indicators and pan-cancer, further elucidating the potential impact of diseases and medication utilization reflected in these indicators on cancer, within the realm of predictive, preventive and personalised medicine(PPPM). Methods To embark on this scientific endeavor, we procured summary-level data from a genome-wide association studies (GWAS) encompassing blood-related indicators and cis-eQTLs of drug target genes, from the esteemed IEU OpenGWAS. Additionally, we obtained GWAS summary-level data encapsulating pan-cancer (consisting of an impressive cohort of 659,582 cases and 12,186,911 controls), along with diseases annotated by their correlation to blood-related indicators, from esteemed sources such as IEU OpenGWAS, UK Biobank, FinnGen, and Biobank Japan. In order to unravel the direct causal associations between blood-related indicators and pan-cancer, as well as the causal implications between the diseases manifested by these indicators and cancer, we initiated a robust analysis employing the two-sample Mendelian randomization(MR) method. Furthermore, utilizing bioinformatics methodologies, we went on to explore the potential effects of drug target genes on pan-cancer. Results Preliminary findings from our MR analysis provided compelling evidence of a significant link between blood-related exposures and pan-cancer. Drawing upon the intriguing interplay observed between blood pressure and tumors, it was postulated that monitoring hypertension (HTN) may offer notable advantages in the prevention of colorectal adenocarcinoma (COAD), breast carcinoma (BRCA), and esophageal carcinoma (ESCA). Similarly, considering the captivating relationship between blood glucose, insulin levels, and tumors, it was hypothesized that closely monitoring diabetes mellitus (DM) could prove beneficial in the prevention of stomach adenocarcinoma (STAD) and COAD. In consonance with the intriguing connection discovered between red blood cell counts, distribution width, and tumors, our findings supported the notion that monitoring anemia could impart advantageous effects in the prevention of lung adenocarcinoma (LUAD). Remarkably, drawing upon the intriguing relationship observed between deep vein thrombosis (DVT) and tumors, it was hypothesized that surveillance of DVT might prove valuable in the prevention of COAD. Additionally, we noted a disparity in risk for various cancers, including lung, breast, colorectal, ovarian, prostate, and pancreatic, consequent to the utilization of drugs for these aforementioned diseases. Among our identified drug targets, we carefully sifted through and diligently analyzed three pivotal genes, namely HMGCR, INSR, and NR3C1, fostering the prospect of formulating novel, tumor-targeted therapeutics. However, our investigation yielded insufficient evidence to confirm any mediating effects of glycated hemoglobin (HbA1c), hemoglobin-gastric, D-dimer, and renin on the associations between HTN, anemia, DVT, DM, and pan-cancer. Conclusions The present study unveils the intricate web of causal associations between blood-related indicators, the diseases they manifest, and medication utilization, all of which significantly impact the development of cancer. Notably, the potential for utilizing blood-related indicators as pioneering biomarkers for cancer prediction and prevention is underscored, showcasing a remarkable avenue for advancing PPPM strategies in the field of oncology. This seminal investigation serves as a beacon of novel insight, engendering the construction of refined and tailored approaches to combat the formidable challenge of cancer.

AIM:Severe painful neuropathy often occurs in cancer patients receiving chemotherapy. Emerging evidence has demonstrated that microglia contribute to the occurrence and development of cancer-associated pain. This study aimed to investigate the mechanisms by which piperine influences cancer-associated pain induced by microglia activation. METHODS:The tumor cell implantation (TCI) model was adopted as the cancer-associated pain model in mice. Behavioral tests were done to confirm that model mice were sensitive to acute mechanical and thermal pain. Western blot (WB) and immunofluorescence (IF) were conducted to quantify expression level of microglia marker protein Iba1 in mice spinal cord tissues. The expression of miR-150-5p and CXCL12 in the mice spinal cord was evaluated by Quantitative real-time Polymerase Chain Reaction (qRT-PCR) and fluorescence in situ hybridization (FISH). Primary microglia from mice were treated with lipopolysaccharide (LPS) to investigate neuroinflammation. RESULTS:The modeled mice showed high susceptibility to acute mechanical hyperalgesia and thermal hyperalgesia. The expression of microglia marker protein Iba1 in the model group was increased in vitro and in vivo. Treatment with piperine effectively relieved the cancer-associated pain in mice. The results of FISH and qRT-PCR showed that piperine significantly increased the expression of miR-150-5p and reduced the expression of CXCL12 in the spinal cord of mice. Furthermore, it inhibited the microglia-induced cancer-associated pain. CONCLUSIONS:Piperine upregulates miR-150-50p levels, inhibits CXCL12 expression, and reduces microglia levels at the lesion site. Therefore, piperine may be a potential drug candidate for the treatment of cancer-associated pain.

铁死亡是一种铁离子依赖性的细胞程序性死亡方式,与铁代谢、脂质代谢及氨基酸抗氧化系统密切相关.铁死亡在肝纤维化发生发展过程中扮演重要角色,可能成为预防和治疗肝纤维化的潜在靶向.研究显示,大量中药成分可通过铁死亡途径抑制肝纤维化.笔者就铁死亡的调控途径、铁死亡在肝纤维化中的作用及治疗策略等方面进行综述,并总结近五年中药单体及活性成分干预铁死亡治疗肝纤维化相关研究,以期为中药干预、抗肝纤维化提供新的思路.

目的:研究周仲瑛教授临床治疗乳腺癌经验及规律.方法:采用Medcase数据处理平台,运用频数规则方法对周仲瑛教授临床治疗乳腺癌的医案进行解构分析,并结合结果运用辨治规律.结果:本研究涉及病例 316 例,1664 诊次,临床症状429 种,病机 181 条,药物344 种,药物种类覆盖 10 大类.结论:周仲瑛教授认为乳腺癌病性总属本虚标实、虚实夹杂,主要病位在肝肾,涉及脾、胃等脏腑;核心证型为气阴两伤、肝肾两虚等;治疗乳腺癌常用药物多为清热类和益气养阴类药物,祛邪药物使用多于扶正药物.

中医体质学说发展历史悠久,最早见于《黄帝内经》,经过不断发展,目前该理论已渐趋成熟,在中医临床诊治疾病过程中发挥了重要作用.中医体质学说认为,体质在疾病的发生、发展、转归等方面均有重要作用.目前,乳腺癌发病率居高不下,已成为威胁女性健康的重要因素.虽然临床治疗乳腺癌手段较多,但是效果多不理想.该文基于中医体质学说探索乳腺癌的易感人群及防治手段,以期为乳腺癌的防治提供新的思路.

ETHNOPHARMACOLOGICAL RELEVANCE:Maimendong and Qianjinweijing Tang (Jin formula) is a traditional Chinese medicine formula that has been proven effective in the treatment of lung cancer in long-term clinical practice. AIM OF THE STUDY:To evaluate the anti-tumor effects of Jin formula combined with cisplatin (JIN + DDP) in vivo and in vitro, as well as to explore the role of long non-coding RNA (lncRNA) in the anti-lung cancer mechanism of its action. MATERIALS AND METHODS:A Lewis lung cancer model was established in C57 BL/6 mice to study the in vivo anti-tumor effect of Jin formula combined with cisplatin. TUNEL staining and western blot were applied to study the effects of Jin formula combined cisplatin on apoptosis. The in vitro anti-cancer function of Jin formula combined with cisplatin was explored by cell viability assay, flow cytometry, wound healing assay and transwell assay. The changes in lncRNA expression profiles were determined by lncRNA microarray, and the differentially expressed lncRNA-p21 was verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. The expression differences of lncRNA-p21 in tumor and normal tissues were analyzed by bioinformatics, and the expression differences of lncRNA-p21 in tumor cells and normal cells were detected by qRT-PCR. The role of lncRNA-p21 in the anti-cancer effect of Jin formula combined cisplatin was investigated by knockdown or overexpression of lncRNA-p21 and a series of cell experiments. The expression of MAPK pathway-related proteins was analyzed by western blot. RESULTS:Jin formula combined with cisplatin (JIN + DDP) can suppress tumor growth and promote apoptosis in Lewis lung cancer mouse model. LncRNA-p21 was significantly up-regulated in the JIN and JIN + DDP groups, and the expression of lncRNA-p21 in lung cancer tissues and cells was lower than that in normal tissues and cells. In vitro, JIN + DDP significantly induced apoptosis and inhibited the proliferation, migration, and invasion of H460 and H1650 lung cancer cells. The above effects can be enhanced by the overexpression of lncRNA-p21 and eliminated by knock-down of lncRNA-p21. Further studies revealed that JIN + DDP inhibited the expression of mitogen-activated protein kinase (MAPK) pathway-related proteins, whereas knock-down of lncRNA-p21 abrogated the inhibition of the MAPK signaling pathway. CONCLUSIONS:This study showed that Jin formula combined with cisplatin could effectively inhibit the progression of lung cancer partially through targeting lncRNA-p21.