The effectiveness of nursing interventions for elderly dementia patients based on virtual reality technology: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the effect of virtual reality technology-based nursing interventions to improve cognitive function, quality of life, activity of daily living, and negative emotions in patients with dementia. METHODS: Computer searches of the VIP Chinese Science and Technology Journal Database, China National Knowledge Infrastructure Database, Wanfang Database, The Cochrane Library, Embase, PubMed, and Web of Science were conducted to include randomized controlled trials and class experimental studies of virtual reality technology-based nursing interventions for patients with dementia, with a search time frame from the date of database creation to March 31, 2023. Two investigators independently screened the literature according to inclusion and exclusion criteria, extracted data, performed risk bias evaluation, and then performed Meta-analysis on the extracted relevant data using Rev Man 5.4 software. RESULTS: A total of 6 randomized controlled trials and 2 quasi-randomized controlled trial with 514 patients with dementia were included. Meta-analysis results showed that compared with conventional cognitive care interventions, virtual reality-based care interventions significantly improved cognitive function [MD = 1.61, 95% CI (0.99, 2.23), Z = 5.12, P < 0.00001], quality of life [SMD = 0.85, 95% CI (0.56, 1.14), Z = 5.70, P < 0.00001] and activity of daily living [MD = 3.75, 95% CI (1.22, 6.28), Z = 2.91, P = 0.004], and alleviate negative emotions [MD = -4.00, 95% CI (-7.26, -0.75), Z = 2.41, P = 0.02]. CONCLUSIONS: The current results suggest that virtual reality-based nursing interventions have a positive effect on improving cognitive function, quality of life, activities of daily living and alleviating negative emotions in patients with dementia. Due to the limitations of the quantity and quality of the included literature, the above findings are yet to be validated by more high-quality studies.

IKKß increases neuropilin-2 and promotes the inhibitory function of CD9+ Bregs to control allergic diseases.

Regulatory B cells (Bregs) potently suppress immune disorders, including allergic contact hypersensitivity (CHS). IKKß overactivation is prominent in various inflammatory diseases. However, its effect on Bregs has not been defined. This study is to investigate the new regulator and inhibitory mechanism of Bregs. IkkßC46A transgenic mice with a Cys46 mutation, resulting in increased IKKß activation, were employed for analysis. IL-10-competent CD9+ Bregs were expanded in IkkßC46A mice and B cell specific-IkkßC46A mutation mice. IkkßC46A mutant CD9+ Bregs had stronger suppressive effects on CD4+ and CD8+ T cells in vitro and CHS responses in vivo. The inhibitory CD9+ Bregs from IkkßC46A mice were characterized by upregulated Neuropilin 2 (Nrp2) and IL-10 in comparison with that of Ikkßwt mice. Interestingly, increased expression of Nrp2 was observed in CD9+ Bregs compared with that of CD9- B cells in wild-type mice. The suppressive activity of wild-type CD9+ Bregs in vitro was attenuated by inhibition of Nrp2 on Bregs or silencing its ligand Sema3f on CD4+ T cells. Our findings delineate a distinct role of IKKß activation in enhancing Bregs to disturb the immune balance. It identifies Nrp2 as a novel regulatory molecule of Bregs that partly contributes to B cell-mediated immune tolerance.

ß-Amyrin ameliorates diabetic nephropathy in mice and regulates the miR-181b-5p/HMGB2 axis in high glucose-stimulated HK-2 cells.

Diabetic nephropathy (DN) is a diabetic complication that can cause renal failure. ß-amyrin has been identified to possess anti-diabetic property. This study was designed to evaluate the potential role of ß-amyrin in DN and its underlying mechanism. Streptozotocin-induced diabetic mice were used as the in vivo model, and high glucose (HG)-stimulated human proximal tubular HK-2 cells were utilized as the in vitro model. Renal histological changes in mice were assessed by hematoxylin-eosin and periodic acid-Schiff staining. HK-2 cell viability and apoptosis were detected by Cell Counting Kit-8 assay and flow cytometry analysis, respectively. ß-amyrin was found to ameliorate kidney injury in DN mice and suppressed inflammatory response as well as apoptosis of HG-stimulated HK-2 cells. miR-181-5p expression in murine renal tissues and HK-2 cells was detected by in situ hybridization (ISH) and fluorescence in situ hybridization (FISH). MiR-181b-5p, a previously identified target for diabetic kidney disease, was downregulated in renal tissues and HG stimulated HK-2 cells, and ß-amyrin induced the upregulation of miR-181b-5p. Binding relationship between miR-181b-5p and high mobility group box 2 (HMGB2) was confirmed by luciferase reporter assay. MiR-181b-5p bound to 3' untranslated region of HMGB2 to suppress its expression. As shown by immunohistochemical staining and immunofluorescence staining, HMGB2 was upregulated in the in vivo and in vitro models of DN, and ß-amyrin induced the downregulation of HMGB2. Moreover, HMGB2 overexpression neutralized the suppressive effects of miR-181b-5p elevation on the inflammatory response and apoptosis of HG-treated HK-2 cells. Overall, ß-amyrin ameliorates DN in mice and suppresses inflammatory response and apoptosis of HG-stimulated HK-2 cells via the miR-181b-5p/HMGB2 axis.

A marine fungus-derived nitrobenzoyl sesquiterpenoid suppresses receptor activator of NF-κB ligand-induced osteoclastogenesis and inflammatory bone destruction.

BACKGROUND AND PURPOSE: Osteoclasts are unique cells to absorb bone. Targeting osteoclast differentiation is a therapeutic strategy for osteolytic diseases. Natural marine products have already become important sources of new drugs. The naturally occurring nitrobenzoyl sesquiterpenoids first identified from marine fungi in 1998 are bioactive compounds with a special structure, but their pharmacological functions are largely unknown. Here, we investigated six marine fungus-derived nitrobenzoyl sesquiterpenoids on osteoclastogenesis and elucidated the mechanisms. EXPERIMENTAL APPROACH: Compounds were first tested by RANKL-induced NF-κB luciferase activity and osteoclastic TRAP assay, followed by molecular docking to characterize the structure-activity relationship. The effects and mechanisms of the most potent nitrobenzoyl sesquiterpenoid on RANKL-induced osteoclastogenesis and bone resorption were further evaluated in vitro. Micro-CT and histology analysis were used to assess the prevention of bone destruction by nitrobenzoyl sesquiterpenoids in vivo. KEY RESULTS: Nitrobenzoyl sesquiterpenoid 4, with a nitrobenzoyl moiety at C-14 and a hydroxyl group at C-9, was the most active compound on NF-κB activity and osteoclastogenesis. Consequently, nitrobenzoyl sesquiterpenoid 4 exhibited suppression of RANKL-induced osteoclastogenesis and bone resorption from 0.5 µM. It blocked RANKL-induced IκBa phosphorylation, NF-κB p65 and RelB nuclear translocation, NFATc1 activation, reduced DC-STAMP but not c-Fos expression during osteoclastogenesis in vitro. Nitrobenzoyl sesquiterpenoid 4 also ameliorated LPS-induced osteolysis in vivo. CONCLUSION AND IMPLICATIONS: These results highlighted nitrobenzoyl sesquiterpenoid 4 as a novel inhibitor of osteoclast differentiation. This marine-derived sesquiterpenoid is a promising lead compound for the treatment of osteolytic diseases.

A mutation of cysteine 46 in IKK-ß promotes mPGES-1 and caveolin-1 expression to exacerbate osteoclast differentiation and osteolysis.

IKK-ß is indispensable for inflammatory osteolysis, the functional residues of IKK-ß are therapeutic drug targets for developing inhibitors to treat multiple diseases now. Thus it remains appealing to find the new residues of IKK-ß to influence osteoclasts for alleviating bone loss diseases such as rheumatoid arthritis (RA). By employing IKK-ß cysteine 46-A transgenic (IKK-ßC46A) mice, we found that mutation of cysteine 46 to alanine in IKK-ß exacerbated inflammatory bone destruction in vivo, and increased osteoclast differentiation and bone resorption ex vivo and in vitro. Consistent with these, IKK-ß kinase activity as well as c-Fos, NFATc1 were up-regulated in bone marrow macrophages (BMMs) from IKK-ßC46A mice during RANKL-induced osteoclastogenesis. Of interesting, we further identified and demonstrated that the expressions of mPGES-1 and caveolin-1 were heightened in BMMs of IKK-ßC46A mice compared to those in WT mice in RANKL-induced osteoclastogenesis. Together, it revealed that mutating cysteine 46 in IKK-ß could increase caveolin-1 and mPGES-1 expression to facilitate osteoclast differentiation and osteolysis. Cysteine 46 can serve as a novel target in IKK-ß for designing inhibitors to treat osteolysis.

IL-10-producing regulatory B cells exhibit functional defects and play a protective role in severe endotoxic shock.

Dysregulated host immune homeostasis in sepsis is life-threatening even after a successfully treated bacterial infection. Lipopolysaccharide (LPS) is an endotoxin that is a major contributor to the aberrant immune responses and endotoxic shock in gram-negative bacterial sepsis. However, the current knowledge of the role of B cells in endotoxic shock is limited. Here, we report that CD1d expression in B cells and the percentage of CD5+CD1dhi regulatory B (Breg) cells decreased in a mouse model of endotoxic shock. Interestingly, IL-10 but not FasL expression in CD5+CD1dhi Breg cells in response to endotoxin was dramatically reduced in severe septic shock mice, and the regulatory function of CD5+CD1dhi Breg cells in vitro to control the Th1 response was also diminished. Adoptive transfer of CD5+CD1dhi Breg cells from healthy WT mice but not IL-10 deficient mice downregulated the IFN-γ secretion in CD4+ T cells and conferred protection against severe endotoxic shock in vivo. Our findings demonstrate the change and notable therapeutic potential of IL-10-producing Breg cells in endotoxic shock.

Sinomenine inhibits osteolysis in breast cancer by reducing IL-8/CXCR1 and c-Fos/NFATc1 signaling.

Sinomenine (SIN) is an anti-inflammatory and antiarthritic alkaloid derived from Sinomenium acutum, and the product Zhengqing Fengtongning produced from SIN has been marketed in China for treating rheumatoid arthritis (RA). Interestingly, we recently found that SIN could significantly ameliorate bone destruction induced by breast cancer cells in mice. Micro-CT examination showed that bone loss of the trabecular bones in tumor-bearing mice was markedly decreased by i.p. treatment of SIN at 150 mg/kg body weight. A mechanistic study demonstrated that SIN could suppress osteoclast formation and bone absorption induced by both MDA-MB-231 cells and MDA-MB-231 cell-conditioned medium (MDA-MB-231 CM) in preosteoclastic RAW264.7 cells. The MDA-MB-231 CM-induced osteoclast-related genes TRAP and OSCAR were obviously downregulated by SIN. In addition, mRNA expression of c-Fos and NFATc1 and nuclear translocation of c-Fos and NFATc1 protein were inhibited by SIN during MDA-MB-231 CM-induced osteoclastogenesis, while NF-κB signaling was not impacted by SIN. More interestingly, SIN was demonstrated to decrease hIL-8 mRNA expression in cultured MDA-MB-231 cells and to inhibit hIL-8 protein expression in MDA-MB-231 cells cocultured with preosteoclastic RAW264.7 cells while simultaneously downregulating CXCR1, the ligand of IL-8 related to bone destruction, during MDA-MB-231 CM-induced osteoclastogenesis. Previously, IL-8/CXCR1 was reported to be associated with the pathogenesis and progression of RA, and SIN was observed to markedly ameliorate bone erosion of RA patients. Our current findings may extend the utilization of SIN to preventing osteoclastogenesis and bone destruction in breast cancer patients and may enable IL-8/CXCR1 to serve as new targets for both anticancer and antiarthritic drug discovery.

B-cell-specific-peroxisome proliferator-activated receptor γ deficiency augments contact hypersensitivity with impaired regulatory B cells.

Nuclear receptor peroxisome proliferator-activated receptor γ (PPAR-γ) activation can prevent immunoinflammatory disorders and diabetes. B cells play protective roles during inflammation as well. However, the roles of endogenous PPAR-γ in the regulatory properties of B cells to relieve inflammation remain unknown. Here, we developed B-cell-specific PPAR-γ knockout (B-PPAR-γ-/- ) mice and found that the conditional deletion of PPAR-γ in B cells resulted in exaggerated contact hypersensitivity (CHS). Meanwhile, interferon-γ (IFN-γ) of CD4+ CD8+ T cells was up-regulated in B-PPAR-γ-/- mice in CHS. This showed that the regulatory function of B cells in B-PPAR-γ-/- mice declined in vivo. Whereas splenic CD5+ CD1dhi regulatory B-cell numbers and peripheral regulatory T-cell numbers were not changed in naive B-PPAR-γ-/- mice. Loss of PPAR-γ in B cells also did not affect either CD86 or FasL expression in splenic CD5+ CD1dhi regulatory B cells after activation. Notably, interleukin-10 (IL-10) production in CD5+ CD1dhi regulatory B cells reduced in B-PPAR-γ-deficient mice. In addition, functional IL-10-producing CD5+ CD1dhi regulatory B cells decreased in B-PPAR-γ-/- mice in the CHS model. These findings were in accordance with augmented CHS. The current work indicated the involvement of endogenous PPAR-γ in the regulatory function of B cells by disturbing the expansion of IL-10-positive regulatory B cells.

Late complications of totally implantable venous access ports in patients with cancer: Risk factors and related nursing strategies.

The aim of this study was to assess the incidence rate and the risk factors for late complications associated with use of central totally implanted venous access devices (TIVAPs) in patients with cancer, and to devise nursing strategies to minimize late complications.This retrospective study included 500 patients with TIVAPs from 2012 to 2015. Multivariable logistic regression analysis was performed to assess the effect of sex, age, primary diagnosis, duration of surgery, and the length of hospital stay on the incidence of late complications of TIVAP.The cumulative maintenance period of TIVAP was 159,605 days. Late complications included catheter-related obstruction (n = 14; 2.8%), infection (n = 3; 0.6%), drug extravasation (n = 1; 0.2%), and catheter exposure (n = 1; 0.2%). Multivariate analyses revealed that age, breast cancer, lung cancer, and gastric cancer were risk factors for the late complications associated with TIVAP.There was a low incidence of late complications with TIVAP use. Catheter-related obstruction is the most frequent late complication of TIVAP. Risk factors for TIVAP-associated late complications include age and certain cancers, such as breast cancer, lung cancer, and gastric cancer.