Differential Characteristics of Fatigue-Pain-Sleep Disturbance-Depression Symptom Cluster and Influencing Factors of Patients With Advanced Cancer During Treatment: A Latent Class Analysis.

BACKGROUND: Patients with advanced cancer may experience symptom clusters during treatment (eg, fatigue, pain, sleep disturbance, depression). Understanding the characteristics and factors associated with symptom cluster classes among this patient population is essential for effective symptom management. OBJECTIVE: The aims of this study were to identify symptom cluster (fatigue-pain-sleep disturbance-depression) classes and explore influencing factors in patients with advanced cancer during the treatment. METHODS: A cross-sectional survey was conducted in an oncology department of a tertiary hospital in China from September 2020 to March 2021. Cancer patients (stage III/IV) 18 years or older completed the questionnaires on pain, fatigue, sleep disturbance, depression, physical activity, and exercise self-efficacy. Latent class analysis and multinomial logistic regression were used. RESULTS: Three hundred sixty-five patients who were male (65.2%) and younger than 60 years (59.5%) completed questionnaires. Three symptom cluster classes were identified: class 1 ("low symptom burden" class), class 2 ("fatigue-insomnia" class), and class 3 ("high symptom burden" class), with a percentage of 54.5%, 38.6%, and 6.8%, respectively. The quality-of-life score, introversion/extroversion, economic burden, Karnofsky Performance Status, albumin level, and exercise self-efficacy were significantly different among the 3 classes (P < .05). CONCLUSION: Patients with advanced cancer were classified into 3 distinct classes, with class 1 having the best function. Results from this study reveal that Karnofsky Performance Status, albumin level, and exercise self-efficacy were significant factors for the latent classes of symptom cluster. IMPLICATIONS FOR PRACTICE: Exercise self-efficacy is important for personalized interventions and improving symptom management efficiency.

Astrocytic purinergic signalling contributes to the development and maintenance of neuropathic pain via modulation of glutamate release.

Although activation of astrocytes is critical in developing neuropathic pain (NP) following nerve injury, the underlying mechanisms of NP and therapeutic management for NP are still vague. Importantly, the decreases in the levels of astrocytic glutamate transporter-1 (GLT-1) in the spinal dorsal horn result in enhanced excitatory transmission and cause persistent pain. P2Y1 purinergic receptor (P2Y1R) has been shown to enhance many inflammatory processes. The up-regulated expression of astrocytic P2Y1R is crucial to participate in pain transduction under conditions of nerve injury and peripheral inflammation considering that P2Y1R is potentially involved in glutamate release and synaptic transmission. This study indicates that the expression of P2Y1R in the spinal cord was increased accompanied by the activation of A1 phenotype astrocytes in the rat model of spinal nerve ligation (SNL). Astrocyte-specific knockdown of P2Y1R alleviated SNL-induced nociceptive responses and mitigated A1 reactive astrocytes, which subsequently increased GLT-1 expression. Conversely, in naïve rats, P2Y1R over-expression induced a canonical NP-like phenotype and spontaneous hypernociceptive responses and increased the concentration of glutamate in the spinal dorsal horn. Besides, our in vitro data showed that the proinflammatory cytokine tumour necrosis factor-alpha contributes to A1/A2 astrocyte reactivity and Ca2+ -dependent release of glutamate. Conclusively, our results provide novel insights that as a significant regulator of astrocytic A1/A2 polarization and neuroinflammation, P2Y1R may represent a potential target for the treatment of SNL-induced NP.

The high burden of symptoms associated with cognitive impairment in lung cancer patients: A latent class analysis.

Objective: To explore the association between the pain-fatigue-sleep disturbance-depression symptom cluster (SC) and cancer-related cognitive impairment (CRCI) in patients having lung cancer and to identify other factors influencing CRCI. Methods: A cross-sectional study was conducted to investigate 378 patients having lung cancer in China from October 2021 to July 2022. The perceived cognitive impairment scale and the general anxiety disorder-7 were used to assess patients' cognitive impairment and anxiety, respectively. The pain-fatigue-sleep disturbance-depression SC was assessed with the brief fatigue inventory, the brief pain inventory, the Patient Health Questionnaire-9, and the Athens Insomnia Scale. Latent class analysis by Mplus.7.4 was used to identify latent classes of the SC. We adjusted for covariates in the multivariable logistic regression model to examine the relationship between the pain-fatigue-sleep disturbance-depression SC and CRCI. Results: Among patients having lung cancer, two SC classes were identified: high and low symptom burden groups. In the crude model, compared to the low symptom burden group, the high symptom group had greater odds of developing CRCI (odds ratio: 10.065, 95% confidence interval: 4.138-24.478). After adjusting for covariates, in model 1, the high symptom group still had greater odds of developing CRCI (odds ratio: 5.531, 95% confidence interval: 2.133-14.336). Additionally, a diagnosis of over 6 months, anxiety, leisure activity, and a high platelet-to-lymphocyte ratio were found to be influencing factors of CRCI (all P â€‹< â€‹0.05). Conclusions: Our study revealed that a high symptom burden is a significant risk factor for CRCI, which may provide a new perspective for managing CRCI in lung patients having cancer.

Hope and depression: the mediating role of social support and spiritual coping in advanced cancer patients.

BACKGROUND: Depression is the most common mental disorder in patients with advanced cancer, which may lead to poor prognosis and low survival rate. This study aims to explore the serial multiple mediating roles of social support and spiritual coping between hope and depression among patients with advanced cancer. METHODS: A cross-sectional study was conducted in China between May and August 2020. A total of 442 advanced cancer patients were investigated by the following self-reported questionnaires: Herth Hope Index (HHI), Spiritual Coping Questionnaire (SCQ, Chinese version), Social Support Rating Scale (SSRS), Hospital Anxiety and Depression Scale (HADS). RESULTS: Depression was negatively correlated with hope, social support, and positive spiritual coping (P < 0.01), and positively correlated with negative spiritual coping (P < 0.01). Hope explained 16.0% of the variance in depression. Bootstrap analyses of the hope--social support--positive spiritual coping--depression showed that there were direct [B = -0.220, 95%CI(- 0.354, - 0.072)] and indirect effects of hope on depression mediated solely by social support [B = -0.122, 95%CI(- 0.200, - 0.066)] and positive spiritual coping [B = -0.112, 95%CI(- 0.217,-0.025)], or by both together [B = -0.014, 95%CI(- 0.038,-0.003)]. Similarly, the hope--social support--negative spiritual coping--depression showed that there were direct [B = -0.302, 95%CI(- 0.404, - 0.190)] and indirect effects of hope on depression mediated solely by social support [B = -0.126, 95%CI(- 0.205, - 0.071)] and negative spiritual coping [B = -0.033, 95%CI(- 0.080,-0.002)], or by both together [B = -0.010, 95%CI(- 0.030,-0.001)]. CONCLUSIONS: This study proves the hypothesis that social support and spiritual coping play intermediary roles between hope and depression. Interventions established through hope, social support and spiritual coping can effectively prevent depression from occurring.

A nomogram to predict prolonged postoperative ileus after intestinal resection for Crohn's disease.

PURPOSE: We aim to identify the risk factors of PPOI in patients with CD and create a nomogram for prediction of PPOI for CD. METHODS: Data on 462 patients who underwent partial intestinal resection for CD in Jin-ling Hospital between January 2019 and June 2021 were retrospectively collected. Univariate and multivariate analyses were performed to determine the risk factors for PPOI and we used the risk factors to create a nomogram. Then we used the Bootstrap-Concordance index and calibration diagrams to evaluate the performance of the Nomogram. Decision curve analysis was performed to evaluate clinical practicability of the model. RESULTS: The incidence of PPOI was 27.7% (n of N). Course of CD ≥ 10 years, operation time ≥ 154 min, the lowest mean arterial pressure ≤ 76.2 mmHg, in-out balance per body weight ≥ 22.90 ml/kg, post-op day 1 infusion ≥ 2847 ml, post-op lowest K+ ≤ 3.75 mmol/L, and post-op day 1 procalcitonin ≥ 2.445 ng/ml were identified as the independent risk factors of PPOI in patients with CD. The nomogram we created by these risk factors presented with good discriminative ability (concordance index 0.723) and was moderately calibrated (bootstrapped concordance index 0.704). The results of decision curve analysis showed that the nomogram was clinically effective within probability thresholds in the 8 to 66% range. CONCLUSION: The nomogram we developed is helpful to evaluate the risk of developing PPOI after partial intestinal resection for CD. Clinicians can take more necessary measures to prevent PPOI in CD's patients or at least minimize the incidence.

The effect of health literacy on patient's perceived shared decision-making among Chinese cancer patients.

OBJECTIVES: To explore the relationship between patient's health literacy and perceived shared decision-making (SDM) among Chinese cancer patients. METHODS: A cross-sectional study was conducted involving a convenience sample of 458 cancer patients from four public hospitals in Guangzhou, China. Patients' self-reported data were collected using the Health Literacy Management Scale (HeLMS) and the nine-item Shared Decision-Making Questionnaire (SDM-Q-9). Hierarchical multiple regressions, controlling for patient-doctor relationship, social support, sociodemographic and clinical variables were conducted to explore the effect of health literacy on perceived SDM. RESULTS: Health literacy itself accounted for 68.0% of the variance in perceived SDM. Higher scores in domains "information acquisition ability," and "communication interaction ability" of HeLMS were significantly associated with a higher level of perceived SDM after controlling the covariates (R2  = 75.7%). CONCLUSIONS: Health literacy, especially the information acquisition ability and communication interaction ability, played a prominent role for Chinese cancer patients to be involved in treatment decision making.

Three-dimensional silk fibroin scaffolds incorporated with graphene for bone regeneration.

Porous three-dimensional (3D) silk fibroin (SF) scaffolds were widely applied for bone regeneration and showed excellent biocompatibility and biodegradability. Recently graphene was developed for bone scaffolds due to its osteogenic properties. Thus, we combine the SF and graphene to improve the osteogenic properties of SF scaffolds. In our study, we explored the incorporation of SF scaffolds with graphene to develop osteogenic scaffolds capable of accelerating bone formation. The 3D SF scaffolds were fabricated with different contents of graphene (0, 0.5, and 2%). Fluorescence images showed that the graphene nanosheets were homogeneously dispersed in the SF scaffolds. The addition of graphene affected the microarchitecture of the scaffolds. The G/SF scaffolds were cocultured with rat bone marrow-derived mesenchymal stem cells (rBMSCs) for 21 days. The cell morphology and cell proliferation study suggested that 0 and 0.5% G/SF scaffolds displayed good cell proliferation. In addition, immunofluorescent staining (e.g., osteonectin, osteopontin, and osteocalcin) and ALP activities indicated that the osteogenic properties was more actively exhibited on 0.5% G/SF scaffolds compared with the other groups. Our results indicated that SF scaffolds incorporated with graphene could be an appropriate scaffold for bone tissue engineering.

Astrocytic NDRG2 is critical in the maintenance of neuropathic pain.

Activation of astrocytes and abnormal synaptic glutamate metabolism are closely associated with the induction and maintenance of neuropathic pain (NP), but the exact mechanism underlying this association remains unclear. N-myc downstream-regulated gene 2 (NDRG2), a novel tumor-suppressor protein and stress-response gene, is involved in the pathogenesis of several neurodegenerative diseases. However, its role in nociceptive transduction has rarely been investigated. Here, we found that NDRG2, which was mainly expressed in the astrocytes in the central nervous system (CNS), was increased in the spinal cord of a spinal nerve ligation (SNL) rat model for NP. Suppression of NDRG2 by intrathecal injection of an NDRG2-RNAi-adenovirus significantly alleviated SNL-induced mechanical and thermal hypersensitivity, as well as elevated astrocytic glutamate transporter 1 (GLT-1) expression and downregulated pro-inflammatory cytokine levels, in the spinal dorsal horn of rats on Day 10 after SNL. Furthermore, in lipopolysaccharide (LPS)-stimulated primary astrocytic cultures derived from neonatal rats, inhibition of NDRG2 significantly reversed both the LPS-induced activation of astrocytes and decreased expression of GLT-1. By contrast, overexpression of NDRG2 by an adenoviral vector carrying NDRG2 resulted in astrocytic activation, aberrant glutamatergic neurotransmission, and spontaneous nociceptive responses in rats. Intrathecal injection of AG490, which is an inhibitor of the Janus tyrosine kinase and signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway, significantly attenuated both mechanical and thermal hyperalgesia, as well as inhibited reactive astrocytes and restored normal expression levels of astrocytic GLT-1, in the spinal dorsal horn of NDRG2-overexpression rats. In conclusion, spinal astrocytic NDRG2 is critical in the maintenance of NP. Moreover, NDRG2 modulates astrocytic activation and inflammatory responses via regulating GLT-1 expression through the JAK/STAT3 signaling pathway. Our findings suggested that NDRG2 could be a novel therapeutic target for the treatment of NP.

Clinical management of cancer-related fatigue in hospitalized adult patients: a best practice implementation project.

OBJECTIVES: This project aimed to identify and promote evidence-based practice in the management of cancer related fatigue (CRF) in the oncology unit of Nanfang Hospital, affiliated with the Southern Medical University in People's Republic of China. INTRODUCTION: Cancer-related fatigue is one of the most common symptoms in patients with cancer and significantly affects their functioning and quality of life. However, it is often inadequately addressed and evidence-based practices are not always followed. METHODS: The Joanna Briggs Institute (JBI) has a validated audit and feedback tool to assist with best practice implementation audits. The JBI Practical Application of Clinical Evidence System (PACES) was used in this project. A three-phase project was undertaken: i) a pre-implementation audit of current practice against evidence-based audit criteria, ii) identification of barriers and implementation of strategies to improve practice using the JBI Getting Research into Practice (GRiP) tool and iii) a post-implementation audit. RESULTS: The baseline audit results identified non-compliance to best practice in all areas of CRF. Strategies to improve practice involved relevant education for nurses, establishment of a CRF management routine and related documentation systems and displaying and distributing educational materials for the patients. Improved compliance was shown across all audit criteria in post-evaluation. CONCLUSIONS: The implementation of institution specific evidence-based resources demonstrated immediate improvement in CRF management and practice. Continuous effort is required to maintain changes and further improve practice. Future projects should focus on measuring the impact of changed practice on patient outcomes.

Targeted cross-linking of the human beta-globin gene in living cells mediated by a triple helix forming oligonucleotide.

Triple helix forming oligonucleotides (TFOs) may have utility as gene targeting reagents for "in situ" gene therapy of genetic disorders. Triplex formation is challenged by negative charge repulsion between third strand and duplex phosphates, and destabilizing positive charge repulsion between adjacent protonated cytosines within pyrimidine motif third strands. Here we describe the synthesis of TFOs designed to target a site in the human beta-globin gene, which is the locus for mutations that underlie the beta-globinopathies, including sickle cell anemia. The target is an uninterrupted polypurine:polypyrimidine sequence, containing four adjacent cytosines, next to a psoralen cross-link site. Pyrimidine motif TFOs that contained four adjacent cytosines or 5-methylcytosines did not form stable triplexes at physiological pH, despite the introduction of otherwise stabilizing base and sugar analogues. We synthesized a series of pso-TFOs containing 2'-O-methyl (OMe) and 2'-O-aminoethoxy substitutions (AE), as well as 8-oxo-adenine (A8) and 2'-O-methylpseudoisocytidine (P) as neutral cytosine replacements. Thermal stability measurements indicated that TFOs with A8 did not meet criteria established in previous work. However, TFOs with P did form triplexes with appropriate T(m) and k(ON) values. A pso-TFO with AE and P residues was sufficiently active to permit the determination of targeting in living cells by direct measurement of cross-link formation at the target site. Our results validate the modification format described in our previous studies and indicate that P substitutions are an effective solution to the problem of targeting genomic sequences containing adjacent cytosines.

Protamine-fragment peptides fused to an SV40 nuclear localization signal deliver oligonucleotides that produce antisense effects in prostate and bladder carcinoma cells.

The development of antisense technology has focused on improving methods for oligonucleotide delivery into cells. In the present work, we describe a novel strategy for oligonucleotide delivery based on a bifunctional peptide composed of a C-terminal protamine-fragment that contains a DNA-binding domain and an N-terminal nuclear localization signal sequence derived from the SV40 large-T antigen (The sequences of two of the peptides are R6WGR6-PKKKRKV [s-protamine-NLS] and R4SR6FGR6VWR4-PKKKRKV [l-protamine-NLS]). We demonstrated, by intrinsic fluorescence quenching, that peptides of this class form complexes with oligodeoxynucleotides. To evaluate delivery, we used a 20-mer phosphorothioate oligomer (Isis 3521) targeted to the 3'-untranslated region of the PKC-alpha mRNA and G3139, an 18-mer phosphorothioate targeted to the first six codons of the human bcl-2 open reading frame, and complexed them with either of two peptides (s- or l-protamine-NLS). These peptides bind to and deliver antisense oligonucleotides to the nucleus of T24 bladder and PC3 prostate cancer cells, as demonstrated by confocal microscopy. Furthermore, as shown by Western and Northern blotting, the peptide-oligonucleotide complexes produced excellent downregulation of the expression of the complementary mRNAs, which in turn resulted in downregulation of protein expression. However, under certain circumstances (predominantly in PC3 cells), incubation of the cells with chloroquine was required to produce antisense activity. Using this strategy, PKC-alpha protein and mRNA expression in T24 and PC3 cells and bcl-2 expression in PC3 cells was reduced by approximately 75 +/- 10% at a minimum concentration of oligomer of 0.25 microM, in combination with 12-15 microM peptide. On the basis of our results, we conclude that arginine-rich peptides of this class may be potentially useful delivery vehicles for the cellular delivery of antisense oligonucleotides. This new strategy may have several advantages over other methods of oligonucleotide delivery and may complement already existing lipid-based technologies.