Proteomic and metabolomic approaches elucidate the molecular mechanism of emodin against neuropathic pain through modulating the gamma-aminobutyric acid (GABA)-ergic pathway and PI3K/AKT/NF-κB pathway.

Neuropathic pain (NeP) is a major health concern. Due to the complex pathological mechanisms, management of NeP is challenging. Emodin, a natural anthraquinone derivative, exerts excellent analgesic effects. However, its mechanisms of action are still poorly understood. In this study, we investigated the mechanisms underlying pain-relief effects of emodin in the cerebral cortex using proteomic and metabolomic approaches. After 15 days of emodin administration, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values in the emodin groups were significantly higher than those in the chronic constriction injury (CCI) group (p < .05), suggesting emodin treatment could reverse CCI-induced hyperalgesia. Emodin treatment evoked the expression alteration of 402 proteins (153 up-regulated and 249 down-regulated) in the CCI models, which were primarily involved in PI3K/AKT signaling pathway, gamma-aminobutyric acid (GABA) receptor signaling, complement and coagulation cascades, cGMP/PKG signaling pathway, MAPK signaling pathway, and calcium signaling pathway. In parallel, emodin intervention regulated the abundance alteration of 27 brain metabolites (20 up-regulated and 7 down-regulated) in the CCI rats, which were primarily implicated in carbon metabolism, biosynthesis of amino acids, pentose phosphate pathway, and glucagon signaling pathway. After a comprehensive analysis and western blot validation, we demonstrated that emodin alleviated NeP mainly through regulating GABAergic pathway and PI3K/AKT/NF-κB pathway.

Emodin inhibits invasion and migration of hepatocellular carcinoma cells via regulating autophagy-mediated degradation of snail and ß-catenin.

BACKGROUND: Previous studies reported that emodin extracted from Rheum palmatum L. exerts antiproliferation and antimetastatic effects in a variety of human cancer types. However, the role of emodin in hepatocellular carcinoma (HCC) remain unknown. METHODS: EdU and colony formation assays were performed to evaluate the effects of emodin on proliferation. The mobility capacities of HCC treated with emodin were evaluated using wound healing assay. Transwell invasion and migration assays were performed to evaluate anti-migratory and anti-invasive effects of emodin on HCC. Annexin V-FITC/PI was performed to analyze the apoptosis. PI stain was performed to analyze cell cycle. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) induced by emodin in HCC. The impact of emodin on autophagic flux in HepG2 cells was examined by mCherry-GFP-LC3 analysis. Western blot was used to assess the protein expressions of epithelial-mesenchymal transition (EMT), autophagy, PI3K/AKT/mTOR and Wnt/ß-catenin signaling pathway. RESULTS: We found that emodin inhibited the growth of HepG2 cells in a dose- and time-dependent manner. In addition, emodin inhibited cell proliferation, induced S and G2/M phases arrest, and promoted apoptosis in HepG2 cells. The migration and invasion of HepG2 cells were also suppressed by emodin. Enrichment analysis revealed that DEGs involved in cell adhesion, cancer metastasis and cell cycle arrest. Moreover, western bolt results show that emodin-induced autophagy promotes Snail and ß-catenin degradation. We also found that blocking autophagic flux after emodin treatment caused EMT reversal. Furthermore, the PI3K agonist Y-P 740 significantly reversed the phosphorylation levels of GSK3ß and mTOR. These results indicated that emodin induced autophagy and inhibited the EMT in part through suppression of the PI3K/AKT/mTOR and Wnt/ß-catenin pathways. CONCLUSION: Our study indicated that emodin inhibited cell metastasis in HCC via the crosstalk between autophagy and EMT.

Molecular subtypes based on DNA methylation predict prognosis in lung squamous cell carcinoma.

BACKGROUND: Due to tumor heterogeneity, the diagnosis, treatment, and prognosis of patients with lung squamous cell carcinoma (LUSC) are difficult. DNA methylation is an important regulator of gene expression, which may help the diagnosis and therapy of patients with LUSC. METHODS: In this study, we collected the clinical information of LUSC patients in the Cancer Genome Atlas (TCGA) database and the relevant methylated sequences of the University of California Santa Cruz (UCSC) database to construct methylated subtypes and performed prognostic analysis. RESULTS: Nine hundred sixty-five potential independent prognosis methylation sites were finally identified and the genes were identified. Based on consensus clustering analysis, seven subtypes were identified by using 965 CpG sites and corresponding survival curves were plotted. The prognostic analysis model was constructed according to the methylation sites' information of the subtype with the best prognosis. Internal and external verifications were used to evaluate the prediction model. CONCLUSIONS: Models based on differences in DNA methylation levels may help to classify the molecular subtypes of LUSC patients, and provide more individualized treatment recommendations and prognostic assessments for different clinical subtypes. GNAS, FZD2, FZD10 are the core three genes that may be related to the prognosis of LUSC patients.

Resilience patterns and transitions in the Be Resilient To Breast Cancer trial: an exploratory latent profile transition analysis.

OBJECTIVE: Be Resilient to Breast Cancer (BRBC), a theoretically-derived, resilience-based, culturally-tailored, supportive-expressive group therapy (SEGT), has been developed to help promote patients' resilience in breast cancer. Data from patients receiving BRBC intervention was utilized to explore and define characteristics of resilience patterns and their transitions over time. METHODS: Resilience was used as a primary outcome and 391 patients completed Resilience Scale Specific to Cancer at enrollment (T0), 2 months (T1), 6 months(T2), and 12 months (T3) after intervention. latent profile transition analysis was performed to model the change in resilience and predict positive transitioning probabilities between resilience patterns (from one pattern to another pattern with a higher level) over time. RESULTS: One hundred and forty four resilience patterns were identified after BRBC intervention. 33.1%, 50.3%, and 40.5% of patients experienced positive resilience transitions from T0 to T1, T1 to T2, and T2 to T3, respectively. Patients with middle age, unmarried status, higher education level, and less advanced tumor stage were more likely to experience positive resilience transitions. CONCLUSION: Different transitions of resilience patterns are observed after BRBC intervention. Age, marital status, education, and tumor stage may be four factors affecting the efficacy of SEGT intervention in breast cancer.

New resilience instrument for family caregivers in cancer: a multidimensional item response theory analysis.

OBJECTIVE: Resilience instruments specific to family caregivers (FCs) in cancer are limited. This study was designed to validate the 10-item Resilience Scale Specific to Cancer (RS-SC-10) in FCs using multidimensional item response theory (MIRT) analysis. METHODS: 382 FCs were enrolled from Be Resilient to Cancer Program (BRCP) and administered with RS-SC-10 and 36-item Short Form Health Survey (SF-36). MIRT was performed to evaluate item parameters while Generalized Additive Model (GAM) and Latent Profile Analysis (LPA) were performed to test the non-linear relationship between resilience (RS-SC-10) and Quality of Life (QoL, SF-36). RESULTS: RS-SC-10 retained 10 items with high multidimensional discrimination, monotonous thresholds and its original two-factor structure (Generic and Shift-Persist). Four latent resilience subgroups were identified and a non-linear dose-response pattern between resilience and QoL was confirmed (per-SD increase OR = 1.62, 95% CI 1.16-2.13, p = 0.0019). CONCLUSION: RS-SC-10 is a brief and suitable resilience instrument for FCs in cancer. The resilience screening of patients and FCs can be performed simultaneously in clinical practice.

Effectiveness of adjuvant supportive-expressive group therapy for breast cancer.

PURPOSE: Randomized control trials exploring adjuvant supportive-expressive group therapy (SEGT) for breast cancer have yielded conflicting survival results. This retrospective cohort study was designed to explore the association of adjuvant SEGT performed at diagnosis with survival in real-world patients. METHODS: 3327 patients with breast cancer were divided between those who received oncologic treatment combined with SEGT-based intervention (referred to as BRBC [n = 354]) and those who only received oncologic treatment (referred to as OT [n = 2973]). Primary outcome was overall survival (OS) at 1-year, 3-year, 5-year. Propensity score-matched analysis (at a ratio of 1:3) and instrumental variable analysis (IVA) were performed. RESULTS: The median overall survival was 7.3 years (95% CI 7.0-7.7 years) in BRBC and 7.1 years (95% CI 6.9-7.4 years) in OT. BRBC was not significantly associated with improved 1-year (HR 0.74, 95% CI 0.49-1.10, P = 0.1748; NNT = 44.8, 95% CI - 118.5 to 22.6), 3-year (HR 0.98, 95% CI 0.75-1.27, P = 0.8640; NNT = 273.7, 95% CI - 21.0 to 21.3), or 5-year survival (HR 0.79, 95% CI 0.61-1.02, P = 0.0908; NNT = 36.0, 95% CI - 384.5 to 19.1) compared with OT. IVA indicated that BRBC had a survival benefit over OT in the 1-year, 3-year, and 5-year of 1.5% (95% CI 1.2-1.9%), 0.7% (95% CI 0.6-0.8%), and 2.6% (95% CI 2.0-3.4%), respectively. CONCLUSION: Adjuvant SEGT cannot significantly prolong 5-year survival in breast cancer, though a longer observation period is warranted according to the marginal survival benefit identified at the end of the follow-up.

Minimum clinical important difference for resilience scale specific to cancer: a prospective analysis.

BACKGROUND: The minimum clinical important differences (MCIDs) of resilience instruments in patients with cancer have not been comprehensively described. This study was designed to evaluate MCIDs of 10-item and 25-item resilience scales specific to cancer (RS-SC-10 and RS-SC-25). METHODS: From June 2015 to December 2018, RS-SCs were longitudinally measured in 765 patients with different cancer diagnoses at baseline (T0) and 3 months later (T1). The EORTC QLQ-C30, Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale, and Allostatic Load Index were measured concurrently as anchors. Anchor-based methods (linear regression, within-group), distribution-based methods(within-group), and receiver operating characteristic curves (ROCs, within-subject) were performed to evaluate the MCIDs. RESULTS: 623 of 765 (84.1%) patients had paired RS-SCs scores. Moderate correlations were identified between the change in RS-SCs and change in anchors (r = 0.38-0.44, all p < 0.001). Linear regression estimated + 8.9 and - 6.7 as the MCIDs of RS-SC-25, and + 3.4 and - 2.5 for RS-SC-10. Distribution-based methods estimated + 9.9 and - 9.9 as the MCIDs of RS-SC-25, and + 4.0 and - 4.0 for RS-SC-10. ROC estimated + 5.5 and - 4.5 as the MCIDs of RS-SC-25, and + 2.0 and - 1.5 for RS-SC-10. CONCLUSIONS: The most reliable MCID is around 5 points for RS-SC-25 and 2 points for RS-SC-10. RS-SCs are more responsive to the worsening status of resilience in patients with cancer and these estimates could be useful in future resilience-based intervention trials.

Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of tongue.

BACKGROUND: Numerous studies have highlighted that long non-coding RNAs (lncRNAs) can bind to microRNA (miRNA) sites as competing endogenous RNAs (ceRNAs), thereby affecting and regulating the expression of mRNAs and target genes. These lncRNA-associated ceRNAs have been theorized to play a significant role in cancer initiation and progression. However, the roles and functions of the lncRNA-miRNA-mRNA ceRNA network in squamous cell carcinoma of the tongue (SCCT) are still unclear. METHODS: The miRNA, mRNA and lncRNA expression profiles from 138 patients with SCCT were downloaded from The Cancer Genome Atlas database. We identified the differential expression of miRNAs, mRNAs, and lncRNAs using the limma package of R software. We used the clusterProfiler package for GO and KEGG pathway annotations. The survival package was used to estimate survival analysis according to the Kaplan-Meier curve. Finally, the GDCRNATools package was used to construct the lncRNA-miRNA-mRNA ceRNA network. RESULTS: In total, 1943 SCCT-specific mRNAs, 107 lncRNAs and 100 miRNAs were explored. Ten mRNAs (CSRP2, CKS2, ADGRG6, MB21D1, GMNN, RIPOR3, RAD51, PCLAF, ORC1, NAGS), 9 lncRNAs (LINC02560, HOXC13 - AS, FOXD2 - AS1, AC105277.1, AC099850.3, STARD4 - AS1, SLC16A1 - AS1, MIR503HG, MIR100HG) and 8 miRNAs (miR - 654, miR - 503, miR - 450a, miR - 379, miR - 369, miR - 190a, miR - 101, and let-7c) were found to be significantly associated with overall survival (log-rank p < 0.05). Based on the analysis of the lncRNA-miRNA-mRNA ceRNA network, one differentially expressed (DE) lncRNA, five DEmiRNAs, and three DEmRNAs were demonstrated to be related to the pathogenesis of SCCT. CONCLUSIONS: In this study, we described the gene regulation by the lncRNA-miRNA-mRNA ceRNA network in the progression of SCCT. We propose a new lncRNA-associated ceRNA that could help in the diagnosis and treatment of SCCT.

Psychometric properties of the Chinese version of resilience scale specific to cancer: an item response theory analysis.

OBJECTIVE: Classic theory test has been used to develop and validate the 25-item Resilience Scale Specific to Cancer (RS-SC) in Chinese patients with cancer. This study was designed to provide additional information about the discriminative value of the individual items tested with an item response theory analysis. METHODS: A two-parameter graded response model was performed to examine whether any of the items of the RS-SC exhibited problems with the ordering and steps of thresholds, as well as the ability of items to discriminate patients with different resilience levels using item characteristic curves. RESULTS: A sample of 214 Chinese patients with cancer diagnosis was analyzed. The established three-dimension structure of the RS-SC was confirmed. Several items showed problematic thresholds or discrimination ability and require further revision. CONCLUSIONS: Some problematic items should be refined and a short-form of RS-SC maybe feasible in clinical settings in order to reduce burden on patients. However, the generalizability of these findings warrants further investigations.

New resilience instrument for patients with cancer.

OBJECTIVE: Resilience is an important concept in the cancer literature and is a salient indicator of cancer survivorship. The aim of this study is to develop and validate a new resilience instrument that is specific to patients with cancer diagnosis (RS-SC) in Mainland China. METHODS: First, a resilience framework was constructed for patients with cancer diagnosis. Second, items were formulated based on the framework to reflect different aspects of resilience. Third, two rounds of expert panel discussion were performed to select important and relevant items. Finally, two cross-sectional studies were conducted to evaluate the psychometric properties of this instrument. RESULTS: Fifty-one items were generated based on the resilience framework and the final 25-item RS-SC resulted in a five-factor solution including Generic Elements, Benefit Finding, Support and Coping, Hope for the Future and Meaning for Existence, accounting for 64.72% of the variance. The Cronbach's α of the RS-SC was 0.825 and the test-retest reliability was 0.874. CONCLUSION: The RS-SC is a brief and specific self-report resilience instrument for Chinese patients with cancer and shows sound psychometric properties in this study. The RS-SC has potential applications in both clinical practice and research with strength-based resiliency interventions.

Effect of a mentor-based, supportive-expressive program, Be Resilient to Breast Cancer, on survival in metastatic breast cancer: a randomised, controlled intervention trial.

BACKGROUND: Because of medical advances, metastatic breast cancer (MBC) is now viewed as a chronic disease, rather than an imminent death sentence. Helping women live with this disease requires more than a medical approach to symptoms. Thus, a mentor-based and supportive-expressive program 'Be Resilient to Breast Cancer' (BRBC) was designed to help Chinese women with MBC enhance their resilience levels, biopsychosocial functions, and potentially extend their life span. METHODS: A total of 226 women with MBC were randomly assigned, in a 1 : 1 ratio, to an intervention group (IG) that participated in BRBC or to a control group (CG) that received no intervention. Be Resilient to Breast Cancer was conducted for 120 min once a week. Primary outcomes were cancer-specific survival and secondary outcomes were resilience, Allostatic Load Index (ALI), anxiety, depression, and quality of life (QoL). The Cox proportional-hazards model was used for survival analysis and growth mixture models were performed for secondary outcomes. RESULTS: Be Resilient to Breast Cancer did not significantly prolong 3- or 5-year survival (median survival, 36.7 months in IG and 31.5 months in CG). The hazard ratio for death was 0.736 (95% CI, 0.525-1.133, P=0.076; univariate Cox model) and 0.837 (95% CI, 0.578-1.211, P=0.345; multivariate Cox analysis). The IG improved in anxiety (ES=0.85, P<0.001), depression (ES=0.95, P<0.001), QoL (ES=0.55, P<0.001), resilience (ES=0.67, P<0.001), and ALI (ES=0.90, P<0.001) compared to CG. CONCLUSIONS: BRBC does not improve survival of women with MBC in this study, though longer follow up is warranted. It positively impacts resilience, QoL, ALI, and emotional distress.

Predicting changes in quality of life and emotional distress in Chinese patients with lung, gastric, and colon-rectal cancer diagnoses: the role of psychological resilience.

BACKGROUND: Patients with cancer often experience considerable emotional distress, which decreases their quality of life (QOL). Resilience is defined as the psychological characteristics that promote positive adaptation in the face of stress and adversity; however, the relationships among QOL, resilience, and emotional distress in patients with cancer, especially Chinese patients with cancer, are under-researched in the literature. METHODS: Quality of Life Questionnaire Core 30 items, Zung Self-Rating Anxiety Scale, and the Zung Self-Rating Depression Scale were applied in this study. Univariate correlated analysis and multivariate logistic regression analysis were used to test the associations among resilience, emotional distress, and QOL with a sample of 276 participants. A Sobel test was conducted to determine whether the indirect effect of resilience was significant. RESULTS: The mean ratings of QOL (59.2), resilience (20.8), anxiety (43.1), and depression (47.7) were reported. The correlations between resilience and QOL in patients with lung cancer were significantly increased compared with patients with gastric or colorectal cancer (Spearman coefficient squares of 0.284, 0.189, and 0.227, respectively). The highest quartile of the resilience level was associated with a 64% (odds ratio = 0.36, 95% confidence interval = 0.17-0.75, P = .006), 70% (odds ratio = 0.30, 95% confidence interval = 0.14-0.63), and 90% (odds ratio = 0.10, 95% confidence interval = 0.04-0.26, P < .001) reduction in the risk of emotional distress compared with the lowest quartile. The Sobel test indicated a buffering effect of resilience that was significant for depression (Sobel value = 2.002, P = .045) but not anxiety (Sobel value = 1.336, P = .182). CONCLUSIONS: The present study suggests that psychological resilience is positively associated with QOL and may comprise a robust buffer between depression and QOL in Chinese patients with cancer.

Effect of an art brut therapy program called go beyond the schizophrenia (GBTS) on prison inmates with schizophrenia in mainland China-A randomized, longitudinal, and controlled trial.

Creative arts therapies are proven to promote an interconnection between body and mind, but there are major obstacles for providing therapeutic services in prisons due to inmates' inherent mistrust for verbal disclosure and rigid self-defenses, especially among inmates with schizophrenia. Thus, we developed a structured and quantitative art brut therapy program called go beyond the schizophrenia to actually measure the benefits of art therapy on prison inmates in mainland China. Upon completion of the program, the intervention group reported a decrease in anxiety, depression, anger, and negative psychiatric symptoms and showed better compliance with rules, socialization with peers, compliance with medications, and regular sleeping patterns after 16 weekly sessions of go beyond the schizophrenia. This article concludes that the art brut therapy was effective for the inmates with schizophrenia in mainland China and provides encouraging data on how to enhance mental health for inmates with schizophrenia. KEY PRACTITIONER MESSAGE: Art brut therapy can reduce emotional distress and negative psychiatric symptoms among Chinese inmates. Arts brut therapy can enhance Chinese inmates' compliance with rules, socialization with peers, compliance with medicines, and regular sleeping patterns. Arts brut therapy in conjunction with medication is highly recommended for recovery of Chinese inmates with schizophrenia, especially for patients with negative symptoms.

Effect of a multidiscipline mentor-based program, Be Resilient to Breast Cancer (BRBC), on female breast cancer survivors in mainland China-A randomized, controlled, theoretically-derived intervention trial.

To reduce the risk of adjustment problems for breast cancer patients in mainland China, we examined the efficacy of a multidiscipline mentor-based program, Be Resilient to Breast Cancer (BRBC), delivered after breast surgery to (a) increase protective factors of social support, hope for the future, etc.; (b) decrease risk factors of Physical and Emotional Distress; and (c) increase outcomes of Resilience, Transcendence and Quality of Life (QOL). A multisite randomized controlled trial was conducted at 6 specialist cancer hospitals. 101 and 103 breast cancer patients were allocated to intervention group (IG) and control group (CG), respectively, and 112 general females (without breast cancer) were allocated to the norm group (NG). Participants completed measures that were related to latent variables derived from the Resilience Model for Breast Cancer (RM-BC) at baseline (T1), 2 months (T2), 6 months (T3), and 12 months (T4) after intervention. At T2, the IG reported significantly lower Depression (ES = 0.65,P = 0.0019) and Illness Uncertainty (ES = 0.57, P = 0.004), better Hope (ES = 0.81, P < 0.001) and QOL (ES = 0.60, P = 0.002) than did the CG. At T3, the IG reported significantly lower Anxiety (ES = 0.74, P < 0.001), better Social Support (ES = 0.51,P = 0.009), Transcendence (ES = 0.87, P < 0.001), and Resilience (ES = 0.83, P < 0.001) compared with the CG. At T4, the IG reported better Resilience though not significant (P = 0.085) and better Transcendence (P = 0.0243) than did the NG. The BRBC intervention improves the positive health outcomes and decreases the risk factors of illness-related distress of breast cancer patients during the high-risk cancer treatment.

Efficacy of acupuncture for a cough-related symptom cluster in patients with lung cancer: A randomized controlled trial.

PURPOSE: This study was designed to evaluate the effect of acupuncture on cough, expectoration, and shortness of breath in lung cancer patients. METHODS: Between December 2021 and June 2022, a total of 130 lung cancer patients were recruited, and they were split into control and intervention groups at random. Routine nursing was provided to the control group, whereas routine nursing with acupuncture using LU7 (Lie Que), LU9 (Tai Yuan), BL13 (Fei Shu), and BL20 (Pi Shu) was administered to the intervention group for 7 days. The severity of cough, expectoration, and shortness of breath was assessed 1 day before and after the interventions using the lung cancer-specific module of the MDASI. A two-way ANOVA was performed for group comparisons. RESULTS: Compared with the control group, the symptoms of cough in the intervention group were significantly improved (F = 5.095, MD = -0.32, 95% CI, -0.59 to 0.04, P = 0.025), while expectoration (F = 0.626, MD = -0.11, 95% CI, -0.38 to 0.16, P = 0.430) and shortness of breath (F = 0.165, MD = -0.05, 95% CI, -0.27 to 0.18, P = 0.685) had no significant change. Cough also identified an obvious interaction effect (P = 0.014), and the post-intervention simple main effect test demonstrated a tangible difference between the two groups (MD = -0.66, 95% CI, -0.99 to 0.33, P < 0.001) post-intervention. CONCLUSIONS: Acupuncture using LU7, LU9, BL13, and BL20 can relieve the cough of lung cancer patients, but not relieve expectoration and shortness of breath.

Brain connectomics improve prediction of 1-year decreased quality of life in breast cancer: A multi-voxel pattern analysis.

PURPOSE: Whether brain connectomics can predict 1-year decreased Quality of Life (QoL) in patients with breast cancer are unclear. A longitudinal study was utilized to explore their prediction abilities with a multi-center sample. METHODS: 232 breast cancer patients were consecutively enrolled and 214 completed the 1-year QoL assessment (92.2%). Resting state functional magnetic resonance imaging was collected before the treatment and a multivoxel pattern analysis (MVPA) was performed to differentiate whole-brain resting-state connectivity patterns. Net Reclassification Improvement (NRI) as well as Integrated Discrimination Improvement (IDI) were calculated to estimate the incremental value of brain connectomics over conventional risk factors. RESULTS: Paracingulate Gyrus, Superior Frontal Gyrus and Frontal Pole were three significant brain areas. Brain connectomics yielded 7.8-17.2% of AUC improvement in predicting 1-year decreased QoL. The NRI and IDI ranged from 20.27 to 54.05%, 13.21-33.34% respectively. CONCLUSION: Brain connectomics contribute to a more accurate prediction of 1-year decreased QoL in breast cancer. Significant brain areas in the prefrontal lobe could be used as potential intervention targets (i.e., Cognitive Behavioral Group Therapy) to improve long-term QoL outcomes in breast cancer.

Systems biology strategy and experimental validation to uncover the pharmacological mechanism of Xihuang Pill in treating non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for almost 85% of lung cancer-related deaths worldwide. Xihuang Pill (XHP) is a representative anticancer Chinese patented medicine used to treat NSCLC in China. However, to date, a systematic analysis of XHP's antitumour effects and its impact on the immune microenvironment has not been performed. PURPOSE: Based on the systems biology strategy and experimental validation, the present study aimed to investigate the pharmacological mechanisms involved in treating NSCLC with XHP. METHODS: A subcutaneous tumour model was established to evaluate XHP's tumour-inhibitory effect in BALB/c nude mice. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to XHP treatment. Network analysis based on network pharmacology and protein-to-protein networks was applied to identify the compounds and genes targeted by XHP. External data from the TCGA-NSCLC cohort were used to verify the clinical significance of XHP-targeted genes in NSCLC. The expression of survival-related candidate genes after XHP treatment was verified via qPCR. The protein expression of calcium voltage-gated channel subunit alpha 1C (CACNA1C) in different NSCLC cell lines was analysed in the Human Protein Atlas database (HPA) and DepMap Portal. Using the Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm and the single-sample gene set enrichment analysis (ssGSEA) algorithm uncovered the role of CACNA1C in the NSCLC tumour microenvironment (TME). RESULTS: XHP (2 g/kg/d) significantly inhibited the growth of transplanted A549 tumours. RNA-seq identified a total of 529 DEGs (189 upregulated and 340 downregulated). In addition, 542 GO terms, 41 significant KEGG pathways, 9 upregulated hallmarks pathways, and 18 downregulated hallmark pathways were enriched. These GO terms and signalling pathways were closely related to cell proliferation, immunity, energy metabolism, and the inflammatory response of NSCLC. In addition, XHP's network pharmacology analysis identified 301 compounds and 1,432 target genes. A comprehensive strategic analysis identified CACNA1C as a promising gene by which XHP targets and regulates the TME of NSCLC, benefiting patient survival. CACNA1C expression was positively correlated with both the immune score and stromal score but negatively correlated with the tumour purity score. Additionally, CACNA1C expression was significantly correlated with the infiltration levels of 15 types of immune cells and the expression levels of 6 well-known checkpoint genes. CONCLUSIONS: Our results show that by regulating the pathways associated with cell proliferation and immunity, XHP can suppress cancer cell growth in NSCLC. Additionally, XHP may increase the expression of CACNA1C to suppress immune cell infiltration and regulate the expression of checkpoint-related genes, thereby improving the overall survival of NSCLC patients.

Measuring resilience by cognitive diagnosis models and its prediction of 6-month quality of life in Be Resilient to Breast Cancer (BRBC).

Objective: The application of advanced Cognitive Diagnosis Models (CDMs) in the Patient Reported Outcome (PRO) is limited due to its complex statistics. This study was designed to measure resilience using CDMs and its prediction of 6-month Quality of Life (QoL) in breast cancer. Methods: A total of 492 patients were longitudinally enrolled from Be Resilient to Breast Cancer (BRBC) and administered with 10-item Resilience Scale Specific to Cancer (RS-SC-10) and Functional Assessment of Cancer Therapy-Breast (FACT-B). Generalized Deterministic Input, Noisy "And" Gate (G-DINA) was performed to measure cognitive diagnostic probabilities (CDPs) of resilience. Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) were utilized to estimate the incremental prediction value of cognitive diagnostic probabilities over total score. Results: CDPs of resilience improved prediction of 6-month QoL above conventional total score. AUC increased from 82.6-88.8% to 95.2-96.5% in four cohorts (all P < 0.001). The NRI ranged from 15.13 to 54.01% and IDI ranged from 24.69 to 47.55% (all P < 0.001). Conclusion: CDPs of resilience contribute to a more accurate prediction of 6-month QoL above conventional total score. CDMs could help optimize Patient Reported Outcomes (PROs) measurement in breast cancer.

Resilience index improves prediction of 1-year decreased quality of life in breast cancer.

BACKGROUND: Resilience is important in cancer survivorship and has great potential to predict long-term quality of life (QoL) in breast cancer. The study was designed to develop a new prediction model to estimate pretest probability (PTP) of 1-year decreased QoL combing Resilience Index (RI) and conventional risk factors. METHODS: RI was extracted from 10-item Resilience Scale Specific to Cancer (RS-SC-10) based on the Principal Component Analysis (PCA). Patients were enrolled from Be Resilient to Breast Cancer (BRBC) and the prediction model was developed based on a sample of 506 consecutive patients and validated in an internal cohort (N1 = 314) and two external cohorts (N2 = 223 and N3 = 189). Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) were utilized to estimate the incremental value of RI. RESULTS: RI improved prediction above conventional risk factors. AUC increased from 0.745 to 0.862 while IDI and NRI were 8.39% and 18.44% respectively (P < 0.0001 for all). Five predictors were included in the final model: RI, age, N stage, M stage, and baseline QoL. The new model demonstrated good calibration ability in the internal and external cohorts resulting in C-indexes of 0.862 (95%CI, 0.815-0.909), 0.828 (95%CI, 0.745-0.910), 0.880 (95%CI, 0.816-0.944), and 0.869 (95%CI, 0.796-0.941). CONCLUSION: RI contributed to a more accurate estimation for PTP of 1-year decreased QoL above conventional risk factors and could help optimize decision making of treatment for breast cancer. IMPLICATIONS FOR CANCER SURVIVORS: A promising prognostic indicator of RI could improve QoL-related management in Chinese patients with breast cancer.