Abstract Background Chemotherapy‐related cognitive impairment (CRCI) is a common but easily overlooked condition that markedly affects the quality of life (QOL) of patients with breast cancer. The rs671 is a common gene polymorphism of aldehyde dehydrogenase 2 ( ALDH2 ) in Asia that is involved in aldehyde metabolism and may be closely related to CRCI. However, no study has yet summarised the association between ALDH2 and CRCI. Methods This study enrolled one hundred and twenty‐four patients diagnosed with breast cancer according to the pathology results, genotyped for ALDH2 single‐nucleotide polymorphisms (SNP) to explore these. The mini‐mental state exam (MMSE), verbal fluency test (VFT), and digit span test (DST) results were compared in these patients before and after chemotherapy (CT). Results We found that patients with ALDH2 gene genotypes of rs671_GG, rs886205_GG, rs4648328_CC, and rs4767944_TT polymorphisms were more likely to suffer from cognitive impairment during chemotherapy. A trend toward statistical significance was observed for rs671_GG of DST (z = 2.769, p = 0.006), VFT ( t = 4.624, P<0.001); rs886205_GG of DST (z = 3.663, P<0.001); rs4648328_CC of DST (z = 2.850, p = 0.004), VFT ( t = 3.477, p = 0.001); and rs4767944_TT of DST (z = 2.967, p = 0.003), VFT ( t = 2.776, p = 0.008). The cognitive indicators of these patients significantly decreased after chemotherapy ( p < 0.05). The difference in ALDH2 rs671 was most obvious. Conclusion Our results showed what kinds of ALDH2 genotyped patients that are more likely to develop CRCI. In the future, it may be possible to infer the risk of CRCI by detecting the single‐nucleotide locus of ALDH2 that is conducive to strengthening clinical interventions for these patients and improving their QOL. More importantly, this study has important implications for Asian women with breast cancer as ALDH2 rs671 is a common polymorphism in Asians.
To evaluate the relationships between psychological distress and immunotherapy efficacy, adverse reactions and quality of life scores in patients with advanced non-small cell lung cancer (NSCLC). A total of 104 NSCLC patients who received 4-6 cycles of standard immunotherapy were enrolled and evaluated with the Distress Thermometer (DT) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The aim was to analyze the correlation between psychological distress and quality of life and to analyze whether psychological distress affects the efficacy of and adverse reactions to immunotherapy. The objective response rate (ORR) and disease control rate (DCR) of the psychological distress group were 6% and 50%, respectively, and those of the no psychological distress group were 18.5% and 83.3%, respectively. The differences were statistically significant (χ2=14.131, P<0.05). The progression-free survival (PFS) of advanced NSCLC patients who received comprehensive immunotherapy and had no psychological distress was significantly better than that of the psychological distress group (HR, 0.338; 95% CI, 0.192-0.592; P<0.05). The PFS of advanced NSCLC patients who received immunotherapy combined with chemotherapy in the no psychological distress group was significantly better than that in the psychological distress group (HR, 0.458; 95% CI, 0.296-0.709; P<0.05). Psychological distress in advanced NSCLC patients affects the efficacy of immunotherapy, and psychological distress is negatively correlated with quality of life during immunotherapy.
Aim: To evaluate the relationship between psychological distress and the efficacy of whole-brain radiotherapy (WBRT) in advanced brain metastasis patients. Methods: Brain metastasis patients (40 with psychological distress and 47 without psychological distress) completed distress thermometer tests before WBRT, and progression-free survival (PFS) was acquired during the follow-up period. Results: Psychological distress was a risk factor for poorer PFS in patients treated with WBRT (p < 0.01). The PFS of survivors who underwent WBRT was superior for those without psychological distress (hazard ratio: 0.295; 95% CI: 0.173–0.500; p < 0.01). Conclusion: The survival of brain metastasis patients receiving WBRT was influenced by psychological distress, which negatively affected the treatment outcome and is likely to be a potential risk indicator in advanced cancer patients receiving WBRT.
Hepatocellular carcinoma is a malignant type of carcinoma with complicated pathogenesis. For HCC patients, there is not only a lack of valuable therapeutic targets, but also a lack of prognostic biomarker. The protein encoded by Aldehyde Dehydrogenase 2 Family Member (ALDH2) is a critical member of the aldehyde dehydrogenase family. Many researchers have found that ALDH2 mutations play an important role in the activation of hepatocellular carcinoma carcinogenic pathways. However, the clinicopathological meaning of ALDH2 in HCC and its relation with immune infiltration is still indistinguishable. In this study, we explored the expression of ALDH2 in 41 HCC tissues by immunohistochemistry. The clinicopathological meaning and molecular function of ALDH2 were analyzed and evaluated through comprehensive bioinformatics. ALDH2 expression in HCC was validated in TCGA, GEO and Oncomine databases, and a survival of ALDH2 based on TCGA database was analysed. LinkedOmics was used to classify the co-expressed genes of ALDH2 and its regulatory factors. The relation between ALDH2 and immune infiltration in HCC was further explored by TIMER. IHC results showed decreased levels of ALDH2 in HCC tumor tissues compared with corresponding normal liver tissues. The pathological grade and prognosis of patients with low expression of the ALDH2 gene were worse. Bioinformatics analysis results showed that ALDH2 was considerably down-regulated in cancer tissues compared with corresponding normal liver tissues in 8 GEO series and TCGA profile (all P<0.05). A nomogram was designed using expression of ALDH2 and clinical factors. ALDH2 was correlated with dendritic cells and macrophages in immune infiltration. In conclusion, ALDH2 has significant prognostic value in hepatocellular carcinoma and they may play key roles in regulating tumor progression and the immune cells infiltration. Our results suggest that ALDH2 may be a new type of tumor biomarker, which can be used to judge the prognosis, targeted therapy and immunotherapy of patients with HCC.
To evaluate the effectiveness and feasibility of Managing Cancer and Living Meaningfully based on VR (VR-CALM), which is used to manage expected symptoms of cancer itself, relieve psychological distress, and improve quality of life (QOL) in the Chinese breast cancer survivors (BCs).Ninety-eight patients with breast cancer were recruited in this study. These patients were randomly assigned to the VR-CALM group or the care as usual (CAU) group. All patients were evaluated by the Functional Assessment of Cancer Therapy-Breast cancer patient (FACT-B), Distress Thermometer (DT), Concerns About Recurrence Scale (CARS), Piper Fatigue Scale (PFS), Pittsburgh Sleep Quality Index (PSQI), The Self-Rating Anxiety Scale (SAS), and The Self-Rating Depression Scale (SDS) before and after VR-CALM or CAU application to BCs. We compared the differences in all these scores between the VR-CALM group and the control group.Patients in the VR-CALM group showed a significant decrease in levels of distress, anxiety, depression, sleep disorders, and fatigue (t = -6.829, t = -5.819, t = -2.094, t = -3.031, t = -10.082, P ≤ 0.001, 0.001, 0.05, 0.01, 0.001, respectively) and had higher level of quality of life (t = 8.216, P ≤ 0.001) compared with the CAU group after intervention. And postintervention patients in VR-CALM group compared with preintervention showed lower level of distress and remarkable improvement of QOL (t = 11.521, t = -10.379, P ≤ 0.001, 0.001). The preintervention questionnaire revealed no significant between-group differences regarding distress, anxiety, depression, sleep disorders, fatigue, and quality of life.VR-CALM is a psychotherapy tailored to the needs of patients with breast cancer. This research innovatively used VR-based CALM intervention to improve psychological and chronic symptoms in BCs. The results of the present study indicate that VR-CALM has salutary effects on the improvement of QOL and relieves psychological distress, anxiety, depression, sleep disorders, and fatigue in BCs.
Chemotherapy related cognitive impairment (CRCI) is a type of memory and cognitive impairment induced by chemotherapy and has become a growing clinical problem. Breast cancer survivors (BCs) refer to patients from the moment of breast cancer diagnosis to the end of their lives. Managing Cancer and Living Meaningfully (CALM) is a convenient and easy-to-apply psychological intervention that has been proven to improve quality of life and alleviate CRCI in BCs. However, the underlying neurobiological mechanisms remain unclear. Resting-state functional magnetic resonance imaging (rs-fMRI) has become an effective method for understanding the neurobiological mechanisms of brain networks in CRCI. The fractional amplitude of low-frequency fluctuations (fALFF) and ALFF have often been used in analyzing the power and intensity of spontaneous regional resting state neural activity.The recruited BCs were randomly divided into the CALM group and the care as usual (CAU) group. All BCs were evaluated by the Functional Assessment of Cancer Therapy Cognitive Function (FACT-Cog) before and after CALM or CAU. The rs-fMRI imaging was acquired before and after CALM intervention in CALM group BCs. The BCs were defined as before CALM intervention (BCI) group and after CALM intervention (ACI) group.There were 32 BCs in CALM group and 35 BCs in CAU group completed the overall study. There were significant differences between the BCI group and the ACI group in the FACT-Cog-PCI scores. Compared with the BCI group, the ACI group showed lower fALFF signal in the left medial frontal gyrus and right sub-gyral and higher fALFF in the left occipital_sup and middle occipital gyrus. There was a significant positive correlation between hippocampal ALFF value and FACT-Cog-PCI scores.CALM intervention may have an effective function in alleviating CRCI of BCs. The altered local synchronization and regional brain activity may be correlated with the improved cognitive function of BCs who received the CALM intervention. The ALFF value of hippocampus seems to be an important factor in reflect cognitive function in BCs with CRCI and the neural network mechanism of CALM intervention deserves further exploration to promote its application.
Abstract The dynamic compression test of geopolymer concrete (GC) before and after water saturation was carried out by the split Hopkinson pressure bar (SHPB). And the effects of water saturation and strain rate on impact toughness of GC were studied. Based on Weibull statistical damage distribution theory, the dynamic constitutive model of GC after water saturation was constructed. The results show that the dynamic peak strain and specific energy absorption of GC have strain rate strengthening effect before or after water saturation. The impact toughness of GC decreases after water saturation. The size distribution of GC fragments has fractal characteristics, and the fractal dimension of GC fragments after water saturation is smaller than that before water saturation. The dynamic constitutive model based on Weibull statistical damage distribution theory can accurately describe the impact mechanical behavior of GC after water saturation, and the model fitting curves are in good agreement with the experimental stress–strain curves.
The aldehyde dehydrogenase 2 point mutation (ALDH2*2) is a common frequent human gene variant, especially in East Asians. However, the expression and mechanism of action of ALDH2 in HNSC remain unknown. The present study explored the clinical significance and immune characteristics of ALDH2 in HNSC. The receiver operating characteristic curve was analysed to assess the diagnostic value of ALDH2 expression. ALDH2 expression in normal tissues and HNSC tissues was evaluated by IHC, and we also analysed ALDH2 gene expression in 4 HNSC cell lines. ALDH2 expression was significantly reduced in HNSC tissues compared to normal tissues (p < 0.05). HNSC patients with high ALDH2 expression had a better prognosis compared to patients with low ALDH2 expression (p < 0.05). GSEA indicated that these gene sets were correlated with signalling pathways, including the JAK-STAT signalling pathway. Unexpectedly, we found a significant prognostic effect of ALDH2 for HNSC based on alcohol consumption and the male sex. The correlation between ALDH2 expression and immune inhibitors showed an effect for ALDH2 in modifying tumour immunology in HNSC, and there may be a possible mechanism by which ALDH2 regulates the functions of T cells in HNSC. In addition, we developed a prognostic nomogram for HNSC patients, which suggested that low ALDH2 expression indicated poor prognosis in HNSC patients who were males and alcoholics.
Abstract Aldehyde dehydrogenase 2 (ALDH2) point mutation ALDH2*2 is the common frequent human gene variant, espically in East Asians. However, nothing is known about their expression and mechanism of action in HNSC. This research tried to explore the clinical significance and immune characteristics of ALDH2 in HNSC. The receiver operating characteristic (ROC) curve was analysed to assessment the diagnostic value of ALDH2 expression. ALDH2 expression in normal tissues and HNSC tissues were evaluated by IHC. Also we analyzed ALDH2 gene expression in 4 HNSC cell lines. ALDH2 expression was significantly reduced in HNSC tissues (p< 0.05). HNSC patients with highly expressed ALDH2 have a better prognosis (p< 0.05). Then, GSEA analysis result pointed that these gene sets were connected with signaling pathways including JAK-STAT signaling pathway. We unexpectedly found a significant prognostic effect of ALDH2 in alcohol consumption and male HNSC patients. The correlation between ALDH2 expression and immunoinhibitors showed a effect for ALDH2 in modifying tumor immunology in HNSC and there may be a possible mechanism by which ALDH2 regulates functions of T cell in HNSC. We developed a nomogram prognostic model for HNSC patients. Moreover, low ALDH2 expression was a poor prognostic factor in male alcoholics of HNSC.
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