Effectiveness of dyadic interventions among cancer dyads: An overview of systematic reviews and meta-analyses.

AIMS AND OBJECTIVE: To summarize evidence from systematic reviews (SRs)/meta-analyses (MAs) regarding the impact of dyadic interventions delivered to both members of a cancer dyad, including a cancer patient and caregiver (e.g. family caregiver, intimate partner). DESIGN: This overview of SRs was conducted in accordance with the preferred reporting items for overviews of reviews statement. METHODS: A comprehensive search of multiple databases, including PubMed, Cochrane Library, Embase, CINAHL, Web of Science, China National Knowledge Infrastructure and Wan Fang. The methodological and reporting quality of SRs and MAs was assessed using the Assessing the Methodological Quality of Systematic Reviews 2. The quality of the included SRs/MAs was evaluated using the Grades of Recommendations, Assessment, Development and Evaluation approach. RESULTS: Eighteen SRs/MAs undertook quantitative synthesis to assess the impact of dyadic interventions on cancer dyads. Both the credibility of the SRs/MAs and the evidence quality of the outcome measures were below satisfactory standards. Prior SRs/MAs revealed several limitations such as lack of pre-published protocols or research objectives, failure to report excluded studies and insufficient details on funding sources for individual studies. CONCLUSIONS: Dyadic interventions may prove advantageous for the physical health and dyadic adjustment of cancer dyads. Nevertheless, the reported results of dyadic interventions on the psychological health of patient-caregiver dyads affected by cancer are inconsistent. Thus, rigorous and comprehensive studies are requisite to establish reliable evidence for conclusive determinations. RELEVANCE TO CLINICAL PRACTICE: The findings of this overview can guide healthcare practitioners when considering the use of dyadic interventions for cancer dyads. Moreover, these findings have the potential to enhance the integration of these approaches into clinical practice. PATIENT OR PUBLIC CONTRIBUTION: Our paper presents an overview of systematic reviews, and therefore, such specific details may not be relevant to our study.

Sleep deprivation during pregnancy leads to poor fetal outcomes in Sprague-Dawley rats.

Sleep deprivation is a common problem during pregnancy, but its impact on the fetus remains unclear. We aimed to investigate the effect of sleep deprivation during pregnancy on fetal outcomes and its mechanism in Sprague-Dawley rats. Sleep deprivation was performed from gestational day(GD) 1-19 using a multiplatform method for 18 h/day. Rats were sacrificed on GD20, and their blood and placentas were collected. Fetal and placental parameters were ascertained. Melatonin, adrenocorticotropic hormone (ACTH) and corticosterone were also measured in serum. The levels of arylalkylamine N-acetyltransferase (AANAT) and two melatonin receptors MT1 and MT2, in placental tissues were detected by western blotting. The inflammatory status and oxidative stress in serum and placentas were investigated. Miscarriage and intrauterine growth restriction were observed in the sleep deprivation group. Sleep deprivation resulted in an increased fetal absorption rate, while fetal weight, crown-rump length and placental weight were reduced. Placental histopathology showed that the labyrinth ratio in the sleep deprivation group was significantly reduced, with hypoplastic villi and obviously decreased blood vessels. Sleep deprivation decreased melatonin in serum and the expression of AANAT, MT1 and MT2 in placental tissues, elevated the oxidative stress products 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde(MDA) in serum and 4-hydroxynonenal (4HNE) in the placenta, and decreased the antioxidants superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in serum. Serum proinflammatory cytokines including interleukin-1-beta (IL-1ß), interleukin-6 (IL-6), necrotizing factor-alpha (TNF-α), and interleukin-8(IL-8), were all elevated by sleep deprivation, and the inflammatory regulatory factor nuclear factor-κB p65 (NF-κB p65) in the placenta was enhanced when examined by immunohistochemistry. Corticosterone levels were comparable between the two groups, although ACTH levels were elevated significantly in the sleep deprivation group. Our study revealed that sleep deprivation during pregnancy can adversely impact fetal outcomes. Melatonin may play an important role in this pathology through the oxido-inflammatory process.

Generation and expression analysis of BAC humanized mice carrying HLA-DP401 haplotype.

Background: Human leukocyte antigen (HLA)-DP is much less studied than other HLA class II antigens, that is, HLA-DR and HLA-DQ, etc. However, the accumulating data have suggested the important roles of DP-restricted responses in the context of cancer, allergy, and infectious disease. Lack of animal models expressing these genes as authentic cis-haplotypes blocks our understanding for the role of HLA-DP haplotypes in immunity. Methods: To explore the potential cis-acting control elements involved in the transcriptional regulation of the HLA-DPA1/DPB1 gene, we performed the expression analysis using bacterial artificial chromosome (BAC)-based transgenic humanized mice in the C57BL/6 background, which carried the entire HLA-DP401 gene locus. We further developed a mouse model of Staphylococcus aureus pneumonia in HLA-DP401 humanized transgenic mice, and performed the analysis on the expression pattern of HLA-DP401 and immunological responses in the model. Results: In this study, we screened and identified a BAC clone spanning the entire HLA-DP gene locus. DNA from this clone was analyzed for integrity by pulsed-field gel electrophoresis and then microinjected into fertilized mouse oocytes to produce transgenic founder animals. Nine sets of PCR primers for regional markers with an average distance of 15 kb between each primer were used to confirm the integrity of the transgene in the five transgenic lines carrying the HLA-DPA1/DPB1 gene. Transgene copy numbers were determined by real-time PCR analysis. HLA-DP401 gene expression was analyzed at the mRNA and protein level. Although infection with S aureus Newman did not alter the percentage of immune cells in the spleen and thymus from the HLA-DP401-H2-Aß1 humanized mice. Increased expression of HLA-DP401 was observed in the thymus of the humanized mice infected by S aureus. Conclusions: We generated several BAC transgenic mice, and analyzed the expression of HLA-DPA1/DPB1 in those mice. A model of Saureus-induced pneumonia in the HLA-DP401-H2-Aß1-/- humanized mice was further developed, and S aureus infection upregulated the HLA-DP401 expression in thymus of those humanized mice. These findings demonstrate the potential of those HLA-DPA1/DPB1 transgenic humanized mice for developing animal models of infectious diseases and MHC-associated immunological diseases.

Epigenetic Landscapes of Single-Cell Chromatin Accessibility and Transcriptomic Immune Profiles of T Cells in COVID-19 Patients.

T cells play a critical role in coronavirus diseases. How they do so in COVID-19 may be revealed by analyzing the epigenetic chromatin accessibility of cis- and trans-regulatory elements and creating transcriptomic immune profiles. We performed single-cell assay for transposase-accessible chromatin (scATAC) and single-cell RNA (scRNA) sequencing (seq) on the peripheral blood mononuclear cells (PBMCs) of severely ill/critical patients (SCPs) infected with COVID-19, moderate patients (MPs), and healthy volunteer controls (HCs). About 76,570 and 107,862 single cells were used, respectively, for analyzing the characteristics of chromatin accessibility and transcriptomic immune profiles by the application of scATAC-seq (nine cases) and scRNA-seq (15 cases). The scATAC-seq detected 28,535 different peaks in the three groups; among these peaks, 41.6 and 10.7% were located in the promoter and enhancer regions, respectively. Compared to HCs, among the peak-located genes in the total T cells and its subsets, CD4+ T and CD8+ T cells, from SCPs and MPs were enriched with inflammatory pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway and tumor necrosis factor (TNF) signaling pathway. The motifs of TBX21 were less accessible in the CD4+ T cells of SCPs compared with those in MPs. Furthermore, the scRNA-seq showed that the proportion of T cells, especially the CD4+ T cells, was decreased in SCPs and MPs compared with those in HCs. Transcriptomic results revealed that histone-related genes, and inflammatory genes, such as NFKBIA, S100A9, and PIK3R1, were highly expressed in the total T cells, CD4+ T and CD8+ T cells, both in the cases of SCPs and MPs. In the CD4+ T cells, decreased T helper-1 (Th1) cells were observed in SCPs and MPs. In the CD8+T cells, activation markers, such as CD69 and HLA class II genes (HLA-DRA, HLA-DRB1, and HLA-DRB5), were significantly upregulated in SCPs. An integrated analysis of the data from scATAC-seq and scRNA-seq showed some consistency between the approaches. Cumulatively, we have generated a landscape of chromatin epigenetic status and transcriptomic immune profiles of T cells in patients with COVID-19. This has provided a deeper dissection of the characteristics of the T cells involved at a higher resolution than from previously obtained data merely by the scRNA-seq analysis. Our data led us to suggest that the T-cell inflammatory states accompanied with defective functions in the CD4+ T cells of SCPs may be the key factors for determining the pathogenesis of and recovery from COVID-19.

Image-localized body surface marking for the intraoperative localization of pulmonary ground-glass nodules.

BACKGROUND: The method of locating pulmonary nodules before operation plays a crucial role in the surgery of pulmonary ground-glass nodules (GGNs). However, the methodologies surrounding intraoperative localization remains limited, with the majority procedures requiring specific additional equipment. We report a new approach in locating pulmonary GGNs by image-localized body surface marking intraoperative (IBMI) localization. METHODS: A retrospective review of the medical records of 76 patients with pulmonary GGNs was performed. All patients underwent IBMI localization between January 2018 and March 2019. Twenty-six patients underwent CT-guided hook wire localization before IBMI localization during surgery. IBMI localization was undertaken directly without pre-treatment in the remaining patients. The efficacy and complications of this approach were analyzed and compared with other pre- or intraoperative localization methods in the current literature. RESULTS: The intraoperative localizations were performed successfully in 72 of all 76 patients pulmonary GGNs within a mean duration of 5.3±1.8 (range, 2.0 to 9.6) minutes. The GGNs in four cases were found to have a significant deviation (>1.5 cm) from the positioning points. All GGNs were successfully resected. Except for five cases of active chest wall bleeding (6.5%), no other intra- or postoperative complications occurred. CONCLUSIONS: The IBMI localization approach is a safe and short-duration procedure with high success rates and fewer complications. We used it for the first time for intraoperative localization of peripheral GGNs with excellent results.

Hepatomas are exquisitely sensitive to pharmacologic ascorbate (P-AscH-).

Rationale: Ascorbate is an essential micronutrient known for redox functions at normal physiologic concentrations. In recent decades, pharmacological ascorbate has been found to selectively kill tumour cells. However, the dosing frequency of pharmacologic ascorbate in humans has not yet been defined. Methods: We determined that among five hepatic cell lines, Huh-7 cells were the most sensitive to ascorbate. The effects of high-dose ascorbate on hepatoma were therefore assessed using Huh-7 cells and xenograft tumour mouse model. Results: In Huh-7 cells, ascorbate induced a significant increase in the percentage of cells in the G0/G1 phase, apoptosis and intracellular levels of ROS. High doses of ascorbate (4.0 pmol cell-1), but not low doses of ascorbate (1.0 pmol cell-1), also served as a pro-drug that killed hepatoma cells by altering mitochondrial respiration. Furthermore, in a Huh-7 cell xenograft tumour mouse model, intraperitoneal injection of ascorbate (4.0 g/kg/3 days) but not a lower dose of ascorbate (2.0 g/kg/3 days) significantly inhibited tumour growth. Gene array analysis of HCC tumour tissue from xenograft mice given IP ascorbate (4.0 g/kg/3 days) identified changes in the transcript levels of 192 genes/ncRNAs involved in insulin receptor signalling, metabolism and mitochondrial respiration. Consistent with the array data, gene expression levels of AGER, DGKK, ASB2, TCP10L2, Lnc-ALCAM-3, and Lnc-TGFBR2-1 were increased 2.05-11.35 fold in HCC tumour tissue samples from mice treated with high-dose ascorbate, and IHC staining analysis also verified that AGER/RAGE and DGKK proteins were up-regulated, which implied that AGER/RAGE and DGKK activation might be related to oxidative stress, leading to hepatoma cell death. Conclusions: Our studies identified multiple mechanisms are responsible for the anti-tumour activity of ascorbate and suggest high doses of ascorbate with less frequency will act as a novel therapeutic agent for liver cancer in vivo.

Gene expression profile in peripheral blood mononuclear cells of postpartum depression patients.

Postpartum depression (PPD) is a common mental health problem that causes maternal suffering and various negative consequences for offspring. The pathogenesis of PPD and the causes of consequences for offspring remain largely unknown. Here, we applied RNA sequencing to sequence the whole transcriptomes of peripheral blood mononuclear cells (PBMCs) from PPD patients (Edinburgh Postnatal Depression Scale [EPDS] score ≥13) and control subjects (EPDS = 0). We found that PPD was positively correlated with multiple genes involved in energy metabolism, neurodegenerative diseases and immune response, while negatively correlated with multiple genes in mismatch repair and cancer-related pathways. Remarkably, genes associated with appetite regulation and nutrient response were differentially expressed between PPD and control subjects. Then, we employed a postnatal growth retardation model by repeated immobilization stress (IS) stimulation to maternal mice. The expression of appetite regulation and nutrient response-related genes in the PBMCs of IS mice and in the hypothalamus of their offspring were also affected. In conclusion, this study provides a comprehensive characterization of the PBMCs transcriptome in PPD and suggests that maternal stress may affect appetite regulation and nutrient response in the hypothalamus of offspring mice.

Overview of the reporter genes and reporter mouse models.

Reporter genes are widely applied in biotechnology and biomedical research owning to their easy observation and lack of toxicity. Taking advantage of the reporter genes in conjunction with imaging technologies, a large number of reporter mouse models have been generated. Reporter mouse models provide systems that enable the studies of live cell imaging, cell lineage tracing, immunological research and cancers etc. in vivo. In this review, we describe the types of different reporter genes and reporter mouse models including, random reporter strains, Cre reporter strains and ROSA26 reporter strains. Collectively, these reporter mouse models have broadened scientific inquires and provided potential strategies for generation of novel reporter animal models with enhanced capabilities.

Anastomosing haemangioma of liver: A case report.

Anastomosing haemangioma (AH) is a recently described, unusual variant of capillary hemangioma that appears to be unique to the genitourinary system, with a particular proclivity for the kidney. AH is a subtype of capillary haemangioma, which is rarely encountered in clinical practice, particularly in the liver. We herein present the case of a 57-year-old woman with an incidental finding on magnetic resonance imaging of a local lesion in the liver, sized 3.3×3.0 cm. The patient underwent hepatectomy with a good postoperative recovery. The histopathological diagnosis was AH of the liver. To the best of our knowledge, this is the first case report of hepatic AH.

Oral administered particulate yeast-derived glucan promotes hepatitis B virus clearance in a hydrodynamic injection mouse model.

Hepatitis B virus (HBV) persistent infection is associated with ineffective immune response for the clearance of virus. Immunomodulators represent an important class of therapeutics, which potentially could be beneficial for the treatment of HBV infection. The particulate yeast-derived glucan (PYDG) has been shown to enhance the innate and adaptive immune responses. We therefore, assessed the efficacy of PYDG in enhancing HBV specific immune responses by employing the hydrodynamic injection-based (HDI) HBV transfection mouse model. Mice were intragatric administered PYDG daily for 9 weeks post pAAV/HBV1.2 hydrodynamic injection. PYDG treatment significantly promoted HBV DNA clearance and production of HBsAb compared to control mice. PYDG treatment resulted in recruitment of macrophages, dendritic cells (DCs) and effector T cells to the liver microenvironment, accompanied by a significantly augmented DCs maturation and HBV-specific IFN-γ and TNF-α production by T cell. In addition, enhanced production of Th1 cytokines in liver tissue interstitial fluid (TIF) was associated with PYDG administration. Live imaging showed the accumulation of PYDG in the mouse liver. Our results demonstrate that PYDG treatment significantly enhances HBV-specific Th1 immune responses, accompanied by clearance of HBV DNA, and therefore holds promise for further development of therapeutics against chronic hepatitis B.

TLR4-dependant immune response, but not hepatitis B virus reactivation, is important in radiation-induced liver disease of liver cancer radiotherapy.

Toll-like receptor 4 (TLR4) is an important trigger of the immune response against hepatitis B virus (HBV) infection and liver injuries. The roles of HBV reactivation versus TLR4-dependant immune response may be critical factors in preventing radiation-induced liver diseases (RILDs) after liver cancer radiotherapy. This study consists of three phases. In the primary phase, livers of mutant TLR4 (TLR4(-)) mice were irradiated with 30 Gy in either the absence or presence of HBV infection. The latter was done by introduction of plasmid pAAV/HBV 1.2. In the advanced phase, RILDs were compared in normal TLR4 (TLR4(+)) versus TLR4(-) mice. In the validation phase, 28 liver cancer patients who had undergone radiotherapy before hepatectomy were enrolled. Liver biopsies near tumors, irradiated with 35-48 Gy, were used to construct tissue microarrays. HBV reactivation, TLR4 expression, and severity of RILDs were studied in both mouse and human. More HBV reactivation, without significant RILD, was observed in irradiated versus unirradiated TLR4(-) mice. RILD scores of TLR4(+) mice were higher than TLR4(-) mice. In humans, serious RILDs tended to develop in patients with high TLR4 expression, but not in patients with low TLR4 or high HBV surface antigen expression. High TLR4 expression was seen in only 2 of 12 HBV-reactive patients, but in HBV-nonreactive patients, it was seen in 6 of 9 (P < 0.03). In summary, RILDs correlated with high TLR4 expression, but not with HBV reactivation, which is inhibited in liver with high TLR4 expression after liver cancer radiotherapy.