Swallowing rehabilitation of patients undergoing T-tube implantation for the treatment of laryngotracheal stenosis.

OBJECTIVE: Patients with laryngotracheal stenosis (LTS) often have dysphagia after laryngotracheal reconstruction with T-tube insertion, which affects the quality of life. The purpose of this study is to observe the effect of swallowing rehabilitation therapy on the improvement of quality of life in patients of otolaryngology-head and neck surgery with dysphagia undergoing T-tube implantation treatment through longitudinal study. METHODS: Thirty-eight patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation were recruited. All patients received swallowing rehabilitation therapy. The assessment of swallowing function was performed using the 10-item Eating Assessment Tool (EAT-10), the 30 mL water swallow test (WST), and flexible endoscopic evaluation of swallow (FEES). RESULTS: After swallowing rehabilitation therapy, timing of swallowing, grade of dysphagia, performance on FEES and 30 mL WST, and EAT-10 score all improved. Thirty-eight patients successfully transitioned to oral feeding and were able to remove their nasogastric tubes without experiencing any complications, including aspiration pneumonia. CONCLUSION: For patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation, swallowing rehabilitation therapy could improve swallowing function of the patients, so as to reduce the potential harm caused by the pain and complications of surgery experienced by patients.

Perceived control, self-management efficacy, and quality of life in patients treated with radiation therapy for breast cancer: a longitudinal study.

OBJECTIVE: This longitudinal study aims to examine the present state of perceived control, self-management efficacy, and overall quality of life (QoL) in patients with breast cancer undergoing radiotherapy, and gain insight into the dynamic trends and factors that influence the quality of life experienced by patients during the course of radiotherapy. METHODS: Participants completed the Cancer Experience and Efficacy Scale (CEES), Strategies Used by People to Promote Health (SUPPH), and Functional Assessment of Cancer Therapy- Breast (FACT-B). The data was analyzed using the software SPSS26.0. Repeated measures analysis of variance (ANOVA) and mixed-effects linear models were used to analyze trends in perceived control, self-management efficacy, and QoL at three-time points, as well as factors affecting QoL during radiotherapy. RESULTS: Perceived control and self-management efficacy were associated with QoL over the course of the radiotherapy. Self-management efficacy (ß = 0.30, P < 0.001), presence of chemotherapy (ß = 18.33, P = 0.024), and duration of illness (ß = 2.25, P = 0.028) had a positive effect on the change in QoL, while time (ß = - 2.95, P < 0.001), cancer experience (ß = - 0.46, P < 0.001), and type of medical insurance (ß = - 2.77, P = 0.021) had the negative effect on the change in QoL. CONCLUSION: The QoL, perceived control, and self-efficacy of patients with breast cancer show dynamic changes during radiotherapy. The higher the self-efficacy, the better the QoL, and the worse the QoL when the sense of disease control is poor. At the same time, more attention should be paid to the QoL of breast cancer radiotherapy patients with a long course of the disease, receiving chemotherapy, and different medical payment methods.

Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis.

Sepsis is a leading cause of in-hospital mortality resulting from a dysregulated response to infection. Novel immunomodulatory therapies targeting macrophage metabolism have emerged as an important focus for current sepsis research. However, understanding the mechanisms underlying macrophage metabolic reprogramming and how they impact immune response requires further investigation. Here, we identify macrophage-expressed Spinster homolog 2 (Spns2), a major transporter of sphingosine-1-phosphate (S1P), as a crucial metabolic mediator that regulates inflammation through the lactate-reactive oxygen species (ROS) axis. Spns2 deficiency in macrophages significantly enhances glycolysis, thereby increasing intracellular lactate production. As a key effector, intracellular lactate promotes pro-inflammatory response by increasing ROS generation. The overactivity of the lactate-ROS axis drives lethal hyperinflammation during the early phase of sepsis. Furthermore, diminished Spns2/S1P signaling impairs the ability of macrophages to sustain an antibacterial response, leading to significant innate immunosuppression in the late stage of infection. Notably, reinforcing Spns2/S1P signaling contributes to balancing the immune response during sepsis, preventing both early hyperinflammation and later immunosuppression, making it a promising therapeutic target for sepsis.

Polydatin radiosensitizes lung cancer while preventing radiation injuries by modulating tumor-infiltrating B cells.

BACKGROUND: Acquired radio-resistance and the undesired normal tissue radiation injuries seriously discount the therapeutic effect of lung cancer radiotherapy. In this study, we aimed to explore the role and potential mechanism of polydatin in simultaneously decreasing radioresistance and radiation injuries. METHODS: The tumor-bearing model of nude mice was used to investigate the tumor inhibition of polydatin on lung cancer and its effect on radiosensitivity, and the effect of polydatin on B cell infiltration in cancerous tissue was investigated. In addition, we performed systemic radiotherapy on BABL/C mice and evaluated the protective effect of polydatin on radiation injury by the Kaplan-Meier survival curve. Moreover, the regulation of polydatin on proliferation and apoptosis of A549 cells was also investigated in vitro. RESULTS: In this study, it is first found that polydatin inhibits the growth and promotes the radiosensitivity of lung cancer while reducing the radiation damage of the healthy tissue. Further, it is evidenced that the major mechanism relies on its regulation on body's immune function, and in particular, the inhibition of radiation-induced B cell infiltration in tumor tissue. CONCLUSION: These findings show that in addition to tumor inhibition, polydatin also promotes the sensitivity and reduces the adverse reactions of radiotherapy, making itself a promising candidate for boosting lung cancer radiotherapy efficacy.

Spirituality as a Mediator Between Social Support and Benefit Finding Among Advanced Cancer Patients.

BACKGROUND: Social support and benefit finding (BF) are important for cancer patients. The relationship between social support and BF has not been studied sufficiently in patients with advanced cancer, and the mechanism through which social support might influence BF is unclear. OBJECTIVE: This study aimed to investigate the relationship between social support and BF in Chinese patients with advanced cancer as mediated by their perceptions of spirituality. METHODS: This was a correlation study with a cross-sectional design. We recruited advanced-cancer patients (n = 208) from China. Patients' sociodemographic and clinical characteristics were collected, and they were asked to complete the Benefit Finding Scale, the Multidimensional Scale of Perceived Social Support, and the Spiritual Attitude and Involvement List. RESULTS: Social support was associated with greater spirituality and greater BF ( P < .01). Spirituality was positively correlated with BF ( P < .01). Results from mediation analysis identified that both the indirect effect of social support on BF via spirituality (indirect effect, 0.268; 95% confidence interval, 0.147-0.419) and its direct effect on BF (direct effect, 0.233; 95% confidence interval, 0.031-0.429) were statistically significant, suggesting a partial mediatory effect of spirituality between social support and BF. CONCLUSIONS: Our findings supported a positive association between social support and BF among Chinese advanced-cancer patients. The mediatory role of spirituality should provide a new perspective for augmentation of BF in these patients. IMPLICATIONS FOR PRACTICE: Interventions that help enhance social support and spirituality in patients with advanced cancer could facilitate their BF.

Fear of progression, loneliness, and hope in patients with gastrointestinal cancer: a cross-sectional relational study.

Introduction: In recent years, fear of disease progression (FoP) has become one of the most common psychological problems in cancer patients. However, there are fewer studies on the FoP in patients with gastrointestinal tumors. We aimed to assess the level of FoP in patients with gastrointestinal tumors and analyze the factors related to FoP. We also aimed to examine the relationship among loneliness, hope and FoP in patients with gastrointestinal cancer. Methods: A cross-sectional survey was conducted on three Grade A hospitals in southwestern China from November 2021 to July 2022. The demographic and clinical characteristics questionnaire, Fear of Disease Progression Scale (FoP-Q-SF), Cancer Loneliness Scale (CLS), and Herth Hope Index (HHI) were included in this study. Data analysis included descriptive statistics, independent samples t-tests, one-way analysis of variance, and multiple linear regression analysis. Results: In total, 245 gastrointestinal cancer patients participated in this study. The average (standard deviation) FoP score in patients was 32.94 ± 10.64. In total, 245 gastrointestinal cancer patients participated in this study. The average (standard deviation) FoP score in patients was 32.94 ± 10.64. The average score of CLS was 17.65 ± 6.71, and that for the HHI was 31.27 ± 7.73. Pearson correlation analysis showed that FoP was negatively significant correlated with hope level (r = -0.522) and FoP was positively significant correlated with loneliness (r = 0.545). Linear regression analysis showed that educational level, age, living condition, hope, and loneliness were the significant predictors of FoP and explained 53.10% of the variability in FoP (F = 16.372). Conclusion: Findings highlight the need to strengthen attention to FoP in gastrointestinal cancer patients. Our study showed that gastrointestinal cancer patients who have a high school education, are age 45 to 59, live alone, high level of loneliness, and low level of hope have higher FoP. Medical staff should enhance clinical screening of FoP and consider the formulation of relevant interventions for high-risk groups to reduce loneliness among patients, raise their hope level, and reduce their FoP.

Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation.

BACKGROUND: Atherosclerosis is a progressive chronic disease characterised by aberrant lipid metabolism and a maladaptive inflammatory response. As atherosclerosis-driven cardiovascular disease remains the major cause of morbidity and mortality worldwide, more effective clinical therapies are urgently needed. Traditional Chinese Medicine (TCM) has demonstrated efficacy against atherosclerosis, with Qing-Xue-Xiao-Zhi formula (QXXZF) having been approved for clinical treatment of patients with atherosclerosis. However, the mechanisms underlying the anti-atherosclerotic activity of QXXZF remain unknown. PURPOSE: To investigate the anti-atherosclerotic effect of QXXZF and reveal its mechanisms using preclinical models. METHODS: In vivo, apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-choline diet (HHD) to induce atherosclerosis. Serum metabolomic profiling was used to identify the concentration of trimethylamine N-oxide (TMAO) in mice. In vitro, RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs) from WT and TLR4-/- C57BL/6 mice were used to explore the effects of QXXZF on macrophages. After confirming the therapeutic effects of QXXZF, mass spectrometry and network pharmacology analyses were used to predict and investigate the main components and the anti-atherogenic mechanisms of QXXZF in the context of atherosclerosis. RESULTS: Our results showed QXXZF significantly suppressed the development of atherosclerosis, as evidenced by the decreased atherosclerotic plaques in the aorta and aortic root, reduced plasma lipid levels and decreased serum TMAO content in HHD-fed ApoE-/- mice. Meanwhile, QXXZF effectively reduced foam cell formation in oxidized low-density lipoprotein (ox-LDL) and TMAO-stimulated RAW264.7 macrophages and BMDMs. Moreover, QXXZF facilitated reverse cholesterol transport (RCT) in macrophages by upregulating the expression of cholesterol efflux-related genes PPARγ/LXRα/ABCA1/ABCG1. Mechanistic studies revealed that QXXZF influenced cholesterol metabolism by inhibiting the TLR4-mediated nuclear factor kappa B (NF-κB) axis. Importantly, TLR4 knockout abolished the influence of QXXZF on macrophages. CONCLUSION: QXXZF promotes lipid efflux and inhibits macrophage-mediated inflammation, producing a therapeutic effect against atherosclerosis. Our study provides new insight into the mechanism of QXXZF against atherosclerosis.

Danhong Injection Attenuates High-Fat-Induced Atherosclerosis and Macrophage Lipid Accumulation by Regulating the PI3K/AKT Insulin Pathway.

BACKGROUND AND AIMS: High-fat diet (HFD) is reported to induce atherosclerosis and insulin resistance. Macrophage lipid accumulation has been implicated as key mediators during the development of HFD-induced atherosclerosis. Traditional Chinese formula, which has long been used to improve disorder of glucose and lipid metabolism of patients, is now gradually being used as complementary therapy. This study aimed to investigate the effect of Danhong injection (DHI), a Chinese medicine used for the treatment of coronary artery disease, on atherosclerosis and its underlying mechanisms. METHODS AND RESULTS: We observed the effects of DHI on HFD-induced atherosclerosis in a mice model, macrophage lipid accumulation in an ox-LDL-stimulated macrophage model, and the role of PI3K/AKT insulin pathway in the process of DHI ameliorating atherosclerosis. The data demonstrated that DHI attenuated atherosclerosis by ameliorating blood lipids, reducing the atherosclerotic index and atherosclerotic plaque area in HFD-induced atherosclerotic mice, and inhibiting TC levels in an ox-LDL-induced macrophage model. By estimating the levels of serum insulin resistance-related indexes and protein expression of GLUT-4, DHI treatment dramatically inhibited the levels of fasting serum NEFA and fasting serum insulin and promoted the protein expression of GLUT-4 in aortas of the HFD-induced atherosclerotic mice. Moreover, according to the hints provided by microarray-based transcriptional profiling, the results demonstrated that DHI treatment also promoted the activation of PI3K/AKT insulin signaling pathway induced by IRS-1 in aortas of HFD-induced atherosclerotic mice. Furthermore, in an ox-LDL-induced macrophage model, the activation of PI3k/AKT signaling pathway also effectively functioned in the process of DHI inhibiting macrophage lipid accumulation. CONCLUSIONS: These results highlight that DHI treatment attenuates atherosclerosis and macrophage lipid accumulation by promoting the activation of PI3K/AKT insulin signaling pathway. It provides new insights into the molecular mechanism of DHI and its therapeutic potential in the treatment of atherosclerosis.

Both glypican-3/Wnt/ß-catenin signaling pathway and autophagy contributed to the inhibitory effect of curcumin on hepatocellular carcinoma.

AIM: The aim of this study is to investigate the role of glypican-3(GPC3)/wnt/ß-catenin signaling pathway and autophagy in the regulation of hepatocellular carcinoma (HCC) growth mediated by curcumin. METHODS: HepG2 cells were treated with various concentrations of curcumin and/or GPC3-targeting siRNA in the presence or absence of 3-MA. Cell proliferation and apoptosis were determined by MTT and TUNEL assay, respectively. Expression of GPC3, ß-catenin, c-myc, LC3, and Beclin1 was determined by western blotting. In addition, curcumin was tested in tumor xenografts mice model, Caliper IVIS Lumina II was used to monitor the tumor growth, and GPC3/wnt/ß-catenin signaling proteins were determined by western blotting. RESULTS: Curcumin treatment led to proliferation inhibition and apoptosis induction in HepG2 cells in a concentration-dependent manner, and suppressed HCC tumor growth in vivo. Further analysis showed that curcumin treatment inactivated Wnt/ß-catenin signaling and decreased GPC3 expression, silencing of GPC3 expression promoted the effects of curcumin on Wnt/ß-catenin signaling. In addition, inhibiting autophagy by 3-MA relieved curcumin-dependent down-regulation of GPC3. CONCLUSION: Curcumin suppressed HCC tumor growth through down-regulating GPC3/wnt/ß-catenin signaling pathway, which was partially mediated by activation of autophagy.

Sphingosine 1-phosphate stimulates eyelid closure in the developing rat by stimulating EGFR signaling.

In many mammals, the eyelids migrate over the eye and fuse during embryogenesis to protect the cornea from damage during birth and early life. Loss-of-function mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway cause an eyes-open-at-birth (EOB) phenotype in rodents. We identified an insertional mutation in Spinster homolog 2 (Spns2) in a strain of transgenic rats exhibiting the EOB phenotype. Spns2, a sphingosine 1-phosphate (S1P) transporter that releases S1P from cells, was enriched at the tip of developing eyelids in wild-type rat embryos. Spns2 expression or treatment with S1P or any one of several EGFR ligands rescued the EOB Spns2 mutant phenotype in vivo and in tissue explants in vitro and rescued the formation of stress fibers in primary keratinocytes from mutants. S1P signaled through the receptors S1PR1, S1PR2, and S1PR3 to activate extracellular signal-regulated kinase (ERK) and EGFR-dependent mitogen-activated protein kinase kinase kinase 1 (MEKK1)-c-Jun signaling. S1P also induced the nuclear translocation of the transcription factor MAL in a manner dependent on EGFR signaling. MAL and c-Jun stimulated the expression of the microRNAs miR-21 and miR-222, both of which target the metalloprotease inhibitor TIMP3, thus promoting metalloprotease activity. The metalloproteases ADAM10 and ADAM17 stimulated EGFR signaling by cleaving a membrane-anchored form of EGF to release the ligand. Our results outline a network by which S1P transactivates EGFR signaling through a complex mechanism involving feedback between several intra- and extracellular molecules to promote eyelid fusion in the developing rat.

Curcumin inhibits hepatitis B virus infection by down-regulating cccDNA-bound histone acetylation.

AIM: To investigate the potential effect of curcumin on hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and the underlying mechanism. METHODS: A HepG2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen (HBsAg) and e antigen (HBeAg) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and cccDNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound cccDNA was detected by chromatin immunoprecipitation (ChIP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs (siRNAs) targeting HBV were tested along with curcumin. RESULTS: Curcumin treatment led to time- and dose-dependent reductions in HBsAg and HBeAg expression and significant reductions in intracellular HBV DNA replication intermediates and HBV cccDNA. After treatment with 20 µmol/L curcumin for 2 d, HBsAg and cccDNA levels in HepG2.2.15 cells were reduced by up to 57.7% (P < 0.01) and 75.5% (P < 0.01), respectively, compared with levels in non-treated cells. Meanwhile, time- and dose-dependent reductions in the histone H3 acetylation levels were also detected upon treatment with curcumin, accompanied by reductions in H3- and H4-bound cccDNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of siRNAs targeting HBV enhanced the inhibitory effects of curcumin. CONCLUSION: Curcumin inhibits HBV gene replication via down-regulation of cccDNA-bound histone acetylation and has the potential to be developed as a cccDNA-targeting antiviral agent for hepatitis B.

The roles of autophagy and apoptosis in burn wound progression in rats.

Understanding the role of cell death in burn wound progression is crucial for giving appropriate diagnoses and designing therapy regimens for burn patients. A well-described and reliable "comb burns model" was employed to evaluate the roles of autophagy and apoptosis in burn wound progression at 2 h, 6 h, 12 h, 24 h, and 48 h post-burn in a rat model. Immunohistochemistry (IHC) results showed that autophagy was detectable in hair follicle epithelium at 2 h post-burn, peaked at 12 h post-burn, then declined. Conversely, apoptosis was mainly located in the stratum epidermis and took place at low levels until 6 h post-burn, at which point it slowly increased. Bcl-2 and Bax, which are regulators of both processes, showed protein expression level patterns that were consistent with the IHC results. This study of autophagy in burn wound tissue progression represents a conceptual expansion of cell death in burn wounds. Based on these results, we suggest that different treatments should be performed on a specific post-burn time course depending on the most prevalent type of cell death occurring at that time.

Experimental investigation of egg ovalbumin scaling on heated stainless steel surface and scale-removal compared with that of whey protein.

Fouling and cleaning on a heat exchanger surface during milk processing have been studied extensively in the past due to their great importance in energy, product quality, and safety. However, little information is available for egg ovalbumin (OVA) fouling and cleaning behavior. In the present work, fouling and cleaning behaviors of OVA were investigated using a real-time monitoring system for heat transfer coefficient. A comparison was made between the behavior of whey protein concentrate (WPC) and that of OVA. WPC has been well studied which can be used as a benchmark. Ultrasonic cleaning was also applied to investigate the cleaning behavior of OVA fouling. Results have shown that OVA created more thermal resistance than WPC in the 2 h fouling process. It was also much more difficult to remove the OVA deposit than the WPC fouling. Different from what were observed from WPC deposit, there was no optimal cleaning rate for OVA deposit in the NaOH concentration range tested (0-2.0 wt%), while WPC fouling is known to have the highest cleaning rate around 0.5 wt% NaOH concentration at moderate temperatures.