Influence of Nurse-Led Health Education on Self-Management Ability, Satisfaction, and Compliance of Elderly Patients with Chronic Obstructive Pulmonary Disease Based on Knowledge, Belief, and Practice Model.

Objective: Knowledge, belief, and behavior model (knowledge-attitude-practice (KAP)) is known as a cognitive model. Health education is important to the prognosis of patients, including chronic obstructive pulmonary disease (COPD) patients. However, the investigation regarding health education based on the KAP model is few. Thus, this work is aimed at analyzing the influence of nurse-led health education on self-management ability, satisfaction, and compliance of elderly patients with COPD based on knowledge, belief, and practice model. Methods: 60 elderly patients with COPD cured in our hospital from January 2019 to April 2021 were enrolled for the study. The patients were randomly assigned to control group (n = 30) and study group (n = 30). The former group received routine nursing, and the latter group accepted health education based on "knowledge, belief, and practice" model. Finally, the scores of nursing satisfaction, KAP score, compliance rate, self-management level, pulmonary function, and life quality were compared in the two groups. Results: The nursing satisfaction of the study group (100.00%) was higher than that (83.33%) of the control group (P < 0.05). The scores of knowledge, attitude, and behavior were remarkably higher in the study group than in the control group after nursing (P < 0.05). Moreover, KAP scores also significantly increased in the study group after nursing. The compliance rate of the study group (93.33%) was higher than that of the control group (66.67%) (P < 0.05). After nursing, the scores of symptom management, daily life management, emotion management, information management, and management efficiency were higher in the study group than in the control group (P < 0.05). In addition, pulmonary functions were improved in the two groups following nursing. Compared with the control groups, the 6 min walking distance, FEV1%, and FEV1/FVC% were higher in the study group (P < 0.05). After nursing, the scores of life quality were reduced in the two groups. The scores of physiological function, psychological function, social function, and health self-cognition were lower in the study group than in the control group (P < 0.05). Conclusion: Based on the model of knowledge, belief, and practice, nurse-led health education can successfully enhance the self-management ability, satisfaction, and compliance of elderly COPD patients.

Differential effects of peptidoglycan on colorectal tumors and intestinal tissue post-pelvic radiotherapy.

Immediate medical intervention is required after pelvic tumor radiotherapy to protect the radiosensitive intestine and also to mitigate tumor growth. Toll-like receptors (TLRs) have been shown to promote tissue repair processes. Here, we analyzed the effect observed upon combining the TLR2 agonist, peptidoglycan (PGN), with radiation therapy on tumors as well as intestinal tissue, both in vitro and in vivo. In contrast to radiotherapy alone, PGN when combined with ionizing radiation (IR) elicited enhanced antitumor effects and also reduced the IR-induced intestinal damage. Mechanistic studies showed that PGN first induced an IL13 response in the irradiated intestine, but was decreased in tumor cell models screened by Th1/Th2 FlowCytomix assay and validated by the application of IL13 and anti-IL13 neutralizing antibodies. Next, PGN stimulated Akt3, but not Akt1/2, as was verified by AKT1/2/3 plasmid transfection assay and in AKT1/2/3 knockout mice in vivo. Akt3 expression was inhibited in 20 µg/mL PGN-treated tumor cells and in 1.5 mg/kg PGN-treated mouse tumor models. However, Akt3 was raised via IL13 in the irradiated intestine and human intestinal cell line after the same treatment. Finally, PGN activated mTOR via IL13/AKT3 in the intestine and restored intestinal structure and function. As an adjuvant to radiotherapy, PGN inhibited tumorigenesis by suppression of mTOR activity. To summarize, the IL13/AKT3/mTOR pathway was lessened in PGN-treated irradiated tumors but was raised in the normal intestine tissue. This distinct effect of PGN on normal and tumor tissues during pelvic radiotherapy suggests that PGN may be a promising adjuvant therapy to radiation.

PD-L1 mediated the differentiation of tumor-infiltrating CD19+ B lymphocytes and T cells in Invasive breast cancer.

Accumulating evidence suggests that B cells play important roles in inhibiting the immune response in autoimmune disorders and human tumors as well as murine tumor models. In an effort to explore the role of B cells in human breast cancer etiology, we examined the presence of CD19+ B lymphocytes in 134 cases of invasive breast carcinoma (IBCa) and 31 breast fibroadenoma, and assessed its relationship with PD-L1 (programmed death-ligand 1) expression in breast cancer. We found that the density of CD19+ B lymphocytes was higher in IBCa compared with fibroadenoma, and significantly associated with increasing tumor grade, negative estrogen status. Similar findings were observed for the expression of IL-10 in IBCa. Meanwhile, CD19+ B lymphocytes were shown to be highly coincident with PD-L1 and IL-10 in IBCa. We further demonstrated that CD19+ B cells can differentiate into CD19+CD24+CD38+ B cells when co-cultured with PD-L1hi MDA-MB231 cells. In addition, the percentage of CD19+CD24+CD38+ B cells was higher in breast tissue and peripheral blood cells of IBCa patients than that of benign tumor and health individuals. And CD19+CD24+CD38+ B cells were found to be IL-10 secreting B cells. Finally, we showed that CD19+ B cells from IBCa patients but not healthy individuals induced formation of CD4+CD25+Foxp3+ T cells when co-cultured with T cells from IBCa patients and healthy subjects (80.4% and 30.8% respectively). The induction of CD4+CD25+Foxp3+ T cells by CD19+ B cells was further shown to be mediated by PD-L1. Together, these results are suggestive of a role for CD19+ B lymphocytes in immune suppression and tumor evasion via PD-L1 in breast cancer.

Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage.

The identification of an agent effective for the treatment of intestinal and bone marrow injury following radiation exposure remains a major issue in radiological medicine. In this study, we evaluated the therapeutic impact of single agent or combination treatments with 2-(3-aminopropylamino) ethylsulphanyl phosphonic acid (WR-2721) and peptidoglycan (PGN, a toll-like receptor 2 (TLR-2) agonist) on radiation-induced injury of the intestine and bone marrow in lethally irradiated male C57BL/6 mice. A dose of 3 mg of WR-2721 per mouse (167 mg/kg, intraperitoneally) was given 30 min before irradiation, and 30 µg of PGN per mouse (1.7 mg/kg) was injected intraperitoneally 24 h after 10 Gy irradiation. Bone marrow cluster of differentiation (CD)45(+) and CD34(+) markers of multiple haematopoietic lineages, number of granulocyte-erythroid-macrophage-megakaryocyte (GEMM) progenitor colonies, bone marrow histopathology, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) expression in the intestines, xylose absorption and intestinal histopathology were all assessed at various time-points after irradiation. Furthermore, nuclear factor kappa B (NF-κB) p65 protein in the ileum was stained by immunofluorescent labelling. PGN-treated irradiated mice showed an increase in CD45(+)CD34(+) cells compared with untreated mice 1.25 days after 10 Gy ionizing radiation (IR) (P < 0.05). Furthermore, combined PGN and WR-2721 treatment had an obviously synergistic radio-protective effect in nucleated cells in the bone marrow, including GEMM progenitors and CD45(+)CD34(+) cells 4 days after 10 Gy IR. Single agent PGN or WR-2721 treatment after 10 Gy IR clearly increased Lgr5-positive pit cells (P < 0.05) and xylose absorption (P < 0.05). However only PGN and WR-2721 combination treatment markedly increased villus height (P < 0.05), number of crypts (P < 0.05) and whole-body weights after 10 Gy whole-body irradiation (WBI). The NF-κB p65 subunit was translocated to the nucleus, and phosphate-IκBα (Ser32/Ser36) was detected after stimulation with either PGN or WR-2721, which indicates that these two agents act synergistically through the activation of the NF-κB pathway. Administration of PGN in combination with WR-2721 was demonstrated to have a synergistic effect on the increase in haematopoietic cells and intestinal reconstitution, as well as improved survival in lethally irradiated mice, but resulted in some degree of an immune disorder.

Apoptosis, necrosis, and autophagy in mouse intestinal damage after 15-Gy whole body irradiation.

Enterocytes die during high-dose radiation exposure in radiation accidents. The modality of cell death has a profound effect on the therapeutic response. The ilea from mice with 15 Gy total body irradiation (TBI) were drawn, morphological features observed by hematoxylin and eosin staining and transmission electron micrographs. The biochemical features of mouse ileum presented with the structure were cleaved Caspase-3 (apoptosis marker), Light Chain 3 (LC3)-I's conversion to LC3-II (autophagy marker) and high mobility group box chromosomal protein 1's secretion (necrosis marker). Then, the autophagy inhibitor (3-methyladenine), caspase inhibitor (Z-VAD-FMK) or necrosis inhibitor (necrostatin) was used to prevent death. Apoptosis, autophagy and necrosis were all appeared in the ileum, but necrosis had the biggest size; the use of 3-methyladenine and Z-VAD-FMK prolong one day's life of the mice after 15 Gy TBI, necrostatin significantly extended the lifespan of 15 Gy irradiated mice (p < 0.05). The results suggest that the death of enterocytes could not be classified into one type of cell death but rather as 'mixed death.'

High expression of survivin in sacral chordoma.

Chordoma is a rare and invasive malignant tumor which primarily relies on surgical treatments. Anticipation of its recurrence and patient survival longevity has been a critical issue of the treatments. This retrospective study examined the survivin expression of sacral chordoma in 30 patients undergoing surgery in our hospital from January 2000 to July 2010, and compared it with chordoma recurrence. Survivin expression was 70 % positive in 30 patients. The positive expression of survivin with recurrence was significantly higher than that without recurrence (p = 0.017) and was inversely related to the continuous disease-free survival time (p < 0.001). Survivin expression was associated with recurrence. The correlation suggested that the survivin expression could be used as an independent predictor of recurrence and could be a potential bio-target gene of angiogenesis in sacral chordoma.

A frequent somatic mutation in CD274 3'-UTR leads to protein over-expression in gastric cancer by disrupting miR-570 binding.

Inhibitory costimulatory molecule CD274 expresses in various cancers and contributes to cancer immune evasion by inhibiting T cell activation and proliferation, yet the regulatory mechanisms for CD274 overexpression in cancers are poorly understood. In this study, we discovered a novel mechanism of CD274 expression regulated by miR-570. A guanine-to-cytosine mutation at the 3'-UTR of CD274 mRNA led to CD274 overexpression by disrupting the miR-570 binding. The mutations were widely observed in cancers by sequencing of 276 gastrointestinal cancers (esophageal, gastric, colorectal, hepatocellular, and pancreatic cancers). This mutation was significantly associated with CD274 overexpression in gastric cancer (P = 1.44×10(-10)) and with the pathological features including differentiation grade, depth of tumor invasion, lymph node metastasis, and tumor-node-metastases (TNM) stage. These findings suggest a novel regulatory mechanism for CD274 overexpression in gastric cancer mediated by miR-570 and a somatic mutation in CD274 3'-UTR, and provide a new insight to gastric carcinogenesis.

Clinicopathologic correlation of cancer stem cell markers CD44, CD24, VEGF and HIF-1α in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study.

CD24(-/low)CD44(+) cells have been identified as putative cancer stem cells (CSCs) in breast cancer. However, the expression of these markers, as well as their association with clinical parameters or tumor microenvironment of breast cancer, remains largely unknown. In the present study, we examined the expression of CD44, CD24, VEGF, and HIF-1α in human breast tumor tissues and assessed their clinicopathological correlations. We investigated tissue samples, including 117 cases of invasive ductal carcinoma (IDCa), 14 cases of ductal carcinoma in situ (DCIS), and 15 cases of intraductal hyperplasia (IDH) from breast tissues. The expression of CD44, CD24, HIF-1α, and VEGF was evaluated using immunohistochemical staining. CD24, CD44, HIF-1α, and VEGF were expressed in 49 (41.9%), 51 (43.6%), 32 (27.4%), and 97 cases (82.9%), respectively, in IDCa. CD24(-/low)CD44(+) cells were noted in 48 (41.3%) cases. The levels of CD24 and VEGF expression correlated positively with tumor malignancy (P<0.05). Meanwhile, the expression of CD24, CD44, and VEGF correlated significantly positively with increasing tumor grade (P<0.05). In addition, associations between CD44 and VEGF, CD24 and VEGF, HIF-1α and VEGF, CD24(-/low)CD44(+) and VEGF, CD24(-/low)CD44(+) and HIF-1α were also observed (P<0.05). The HIF-1α expression level was relatively higher in early stage breast cancer patients with CD24(-/low)CD44(+) cells. Taken together, our results suggest that CD24 and VEGF may play important roles in breast tumorigenesis and progression, while HIF-1α may play a role in the early stage of breast carcinogenesis.

Expression of vascular endothelial growth factor and matrix metalloproteinase-9 in sacral chordoma.

Sacral chordoma is a vessel-rich and infiltrative tumor, but the fundamental knowledge of its biological behavior remains unknown. This study was designed to investigate the expression levels and contributions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the angiogenesis and recurrence of sacral chordoma and their correlations. An immunohistochemical method was used to investigate the expression of VEGF, MMP-9, and microvascular density (MVD) in 36 patients with sacral chordoma. Their differences in expressions were statistically analyzed and their correlations with angiogenesis and recurrence were evaluated. The mean MVD of sacral chordomas was significantly higher than that of the adjacent normal tissues (P = 0.033). Immunoreactivity for VEGF and MMP-9 was significantly higher in sacral chordoma tissues than in adjacent normal tissues (P = 0.008, P = 0.005). The mean MVD of VEGF and MMP-9 were statistically higher in positive group than in negative group (P = 0.015, P = 0.004), respectively . Moreover, a significant correlation was found between the VEGF and MMP-9 (P = 0.002). The log-rank test revealed that continuous disease-free survival time (CDFS) was significantly shorter in the MMP-9-positive group than in the MMP-9-negative group (P = 0.019), but the difference in the VEGF-positive group and the VEGF-negative group was not statistically significant (P = 0.938). Our data suggest that VEGF and MMP-9 might act with a synergistic effect and can positively regulate the angiogenesis in sacral chordoma. Positive expression of MMP-9 might indicate the local recurrence of sacral chordoma. The result suggests that some specific drugs which inhibit VEGF, MMP-9, or their receptors may have a good therapeutic effect for sacral chordoma.

Costimulatory molecule OX40/OX40L expression in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study.

OX40, a membrane-bound member of the tumor-necrosis-factor-receptor (TNFR) superfamily, plays an important role in proliferation, survival and infiltration of activated T cells via binding to OX40L. Recent studies indicate that OX40/OX40L system mediates the adhesion and infiltration of adult T cell leukemia (ATL). Previously, we detected OX40 expression in breast carcinoma cell lines and tissues. The correlation of expression of OX40 and OX40L and clinical features in breast carcinogenesis, however, has not been well characterized. The expression of OX40 and OX40L in 107 invasive ductal carcinomas (IDCa), 9 ductal carcinomas in situ (DCIS), and 31 fibroadenomas from breast tissues and its relationship with the clinical features were determined using immunohistochemistry (peroxidase-conjugated polymer method, ChemMate™ Envision™ Detection kit). The positive immunostaining rates for OX40 in IDCa, DCIS and fibroadenomas from breast tissues were 85.0%, 66.7% and 38.7% respectively, showing a significant difference in OX40 expression among IDCa, DCIS and fibroadenoma of breast (z=5.206, P=0.001). Increased staining intensity of OX40 was associated with TNM stages (z=2.112, P=0.017). Meanwhile, a relation of OX40 expression with lymph node metastatic status in IDCa was found (P=0.041). The expression of OX40L did not show any obvious difference among IDCa, DCIS and fibroadenomas from breast tissues. OX40L expression was also not related to histopathological parameters in IDCa except for progesterone receptor (PR) being positive (P=0.005). However, a high coincidental positive rate for OX40 and OX40L was observed in biopsy samples with IDCa (P=0.017, Kappa=0.231). The present results suggest that high OX40 expression may be associated with malignant transformation, progression, invasion and metastasis in breast cancer biology.

CD40 is a regulator for vascular endothelial growth factor in the tumor microenvironment of glioma.

CD40 is expressed in many tumor cells, however, its role in tumor biology is yet to be demonstrated. In the present study, we investigated the role of CD40 in gliomas. In vivo, we evaluated CD40 expression in 95 glioma tissues and 10 non-tumorous brain tissues and investigated the relationship between histopathological parameters, vascular density, and vascular endothelial growth factor (VEGF) expressions. In vitro, we aimed to understand the biological relevance of CD40 and VEGF in glioma cell lines. The results clearly demonstrated that CD40 expression, including membranous and cytoplasmic staining, was significantly higher in poorly differentiated and well differentiated gliomas than in the non-tumorous brain tissues (P=0.045 and P=0.043, respectively). In gliomas, the expression of CD40 was significantly correlated with tumor size, VEGF expressions and microvessel density (MVD) (P=0.022, P=0.023 and P=0.0316, respectively). In the in vitro study, stimulation of human glioma cells by CD40 ligation induced the expression and secretion of VEGF and was blocked by anti-CD40 monoclonal antibody. These observations provide evidence that CD40 ligation supports the expression and secretion of VEGF and may be involved in neovascularization of gliomas, they also suggest that CD40 and VEGF may be useful biomarkers for evaluating the risk of developing gliomas, and may also be used as a target for therapy.

Selection of optimal sites for TGFB1 gene silencing by chitosan-TPP nanoparticle-mediated delivery of shRNA.

Most human tumors produce high levels of TGF-beta1, whose autocrine and paracrine actions promote tumor cell invasiveness and metastasis. Currently, many experimental therapies that target TGFB1 have utilized antisense DNA or RNA interference (RNAi). Despite the great potential of RNAi, the selection of effective target sites and proper delivery systems for short hairpin RNA (shRNA) remains a significant issue. Here, we used chitosan nanoparticle-mediated delivery of a shRNA-expressing vector to inhibit TGFB1 expression in the human rhabdomyosarcoma cell line RD. Knockdown of TGFB1 by shRNA resulted in a decrease in RD cell growth in vitro and tumorigenicity in nude mice. The efficiency of TGFB1 gene silencing varied with the selection of targeting sites. These data suggest that chitosan nanoparticle-mediated delivery of an shRNA produces efficient TGFB1 knockdown in rhabdomyosarcoma cells and may be a method of choice for shRNA delivery for gene therapy.

[Establishing an organic model of SMC proliferation with cultured aorta of rats and exploring the underlying mechanism].

To study the mechanism of proliferous vascular disease as well as its prevention and treatment, an organic model was established with cultured aortas of rats, and the mechanism there-in invloved was probed. Immunostaining histology showed that smooth muscle cell (SMC) proliferation was observed in the aorta segments of rats, after their endothelia being injured and cultured in vitro with 20% fetal bovine serum. After being cultured for 5 days, various degrees of proliferation of SMC on cultured artery segments were observed by HE staining, and conspicuous plaques were developed after being cultured for 13 days. The proliferous SMC was also observed by Brdu labeling. RT-PCR examination showed that the mRNA expression of hypertension-related gene-1 (Hrg-1) and smooth muscle 22 alpha (SM22a) in the aortas decreased with the prolongation of culture time, and completely disappeared after being cultured for 13 days . But when cultured in vitro for ten days, the ET-1 content of supernatant and the proliferous SMC labeled by Brdu increased obviously and the expressions of Hrg-1 and SM22a decreased after the endothelium was destroyed. Compared with the injured endothelium groups, the proliferous SMC of injured endothelium plus BQ123 groups decreased visibly. The same significant differences between serum groups and serum-free groups were also observed. These results suggest that the culturing of rat aorta segments in vitro can induce the proliferation of SMC and the transform of phenotype from contractile type to synthetic type. The ET-1 and serum are the main factors in the proliferation of SMC and in the transform of phenotype. This organic model could serve as a good experimental platform for the researches into the mechanism of proliferous vascular disease as well as its prevention and treatment.

A novel cultured tissue model of rat aorta: VSMC proliferation mechanism in relationship to atherosclerosis.

Development of a cultured tissue experimental model of rat aorta was explored in order to study mechanism of vascular smooth muscle (VSMC) proliferation. This particular model has potential with regard to amelioration of atherosclerosis and other vascular diseases in comparison to whole animal and cell culture models. The aorta segments of rats were divided into 4 experimental groups: the injured endothelium, injured endothelium plus BQ123, without injured endothelium and without injured endothelium plus BQ123. Each of group was subdivided into a further 2 subgroups and cultured with 20% serum and with serum-free DMEM. Each group cultured in vitro for 5, 8 and 13 days respectively. The control group was not cultured in vitro. Bromodeoxyuridine (BrDU 8x10(-4) mol/l) was added into the cultured medium of all groups, 24 h prior to harvesting. These segments were fixed in 4% paraformaldehyde for paraffin slice used to HE and immunocytochemical staining and other aorta segments were used to detect the expressions of hypertension-related gene-1 (HRG-1) and smooth muscle 22 alpha (SM22alpha) by RT-PCR. ET-1 content in the supernatant was detected with radioimmunology. Proliferous VSMC can be observed on artery segments cultured in vitro, and conspicuous plaques were developed on model vascular wall cultured for 13 days. Labeled cells increased with an increase in culture time but were not seen in the control group. A greater number of labeled cells were observed in injured endothelium group cultured in 20% serum DMEM. Hyperplasia was inhibited after BQ123 was added into the medium, suggesting that serum and ET-1 are important factors that lead to VSMC proliferation. Expressions of HRG-1 and SM22alpha were decreased while the aorta segments were cultured in vitro, minimum or even absent mRNA expressions of HRG-1 and SM22alpha were detected in injured endothelium cultured in 20% serum DMEM and increased in injured endothelium plus BQ123 group cultured. ET-1 content in the supernatant increased in injured endothelium cultured in 20% serum DMEM. These results show that the phenotypic transform and VSMC proliferation on cultured artery segments were related not only to serum culture, but also to ET-1 secreting. ET-1 and serum may be the main factors of contributing to the proliferation and phenotypic transform. This model provides a favorable experimental platform for research into the mechanism of vascular proliferous diseases as well as its prevention and treatment.

Analysis of costimulation by 4-1BBL, CD40L, and B7 in graft rejection by gene expression profiles.

Recent studies affirm costimulatory blockade as a beneficial means of preventing allograft rejection. The precise molecular effects of these pathways, however, are not entirely understood. A striking example is in the costimulatory pathways, 4-1BB/4-1BBL, CD40/CD40L, and B7/CD28. Blocking any one of these prolongs graft survival, yet each operates via distinct immunomodulatory signals. To examine the mechanistic relationships among these signals, our approach was a comprehensive investigation of their molecular constituents. Using a model of heterotopic heart transplantation in mice with a costimulatory pathway deficiency, we analyzed the expression profiles of a large panel of immune and inflammatory genes using ribonuclease protection assays coupled with algorithms. We found that while graft survival was prolonged in all groups, each pathway modulates a unique profile of expressed genes. There were 19 genes, for example, with significant changes in expression compared to the control, yet none of these were similarly modulated in all three groups. Our study reveals that despite similar delays of allograft rejection, the molecular basis for this effect is distinct in all three costimulatory pathways. Furthermore, we underscore the existence of numerous molecular mechanisms affecting graft survival. This, in turn, provides crucial implications for clinical treatment post-transplant where inhibitors would be designed to target multiple mechanisms.

Insulin sensitivity after pancreaticoduodenal transplantation with systemic and portal venous drainage in inbred rats.

OBJECTIVE: To assess the metabolic consequences of pancreatic transplantation with portal venous drainage and systemic venous drainage in induced inbred rats with streptozocin. METHODS: Pancreaticoduodenal transplantation was performed on 8 rats with the donor portal veins anastomosed to the recipient superior mesenteric vein and on 10 rats with the donor portal veins anastomosed to the recipient cava inferior vein. We measured the recipients' weight, urine and plasma glucose concentration, plasma insulin concentration at the beginning, and before and after transplantation. We used the euglycemi-hyperinsulinemic glucose clamp test and glucose infusion required as an index of insulin sensitivity. RESULTS: The plasma glucose and insulin concentration recovered to normal after transplantation in the portal venous drainage group. The plasma insulin levels increased in the systemic venous group after transplantation. There was a difference in the glucose infusion required between the two groups. CONCLUSION: These data imply that portal venous drainage of the transplanted pancreas is an important factor in the determination of peripheral insulin sensitivity.