Psilostachyin C reduces malignant properties of hepatocellular carcinoma cells by blocking CREBBP-mediated transcription of GATAD2B.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally. Many herbal medicines and their bioactive compounds have shown anti-tumor properties. This study was conducted to examine the effect of psilostachyin C (PSC), a sesquiterpenoid lactone isolated from Artemisia vulgaris L., in the malignant properties of HCC cells. CCK-8, flow cytometry, wound healing, and Transwell assays revealed that 25 µM PSC treatment significantly suppressed proliferation, cell cycle progression, migration, and invasion of two HCC cell lines (Hep 3B and Huh7) while promoting cell apoptosis. Bioinformatics prediction suggests CREB binding protein (CREBBP) as a promising target of PSC. CREBBP activated transcription of GATA zinc finger domain containing 2B (GATAD2B) by binding to its promoter. CREBBP and GATAD2B were highly expressed in clinical HCC tissues and the acquired HCC cell lines, but their expression was reduced by PSC. Either upregulation of CREBBP or GATAD2B restored the malignant properties of HCC cells blocked by PSC. Collectively, this evidence demonstrates that PSC pocessess anti-tumor functions in HCC cells by blocking CREBBP-mediated transcription of GATAD2B.

Injectable Oxygen-Carrying Microsphere Hydrogel for Dynamic Regulation of Redox Microenvironment of Wounds.

The delayed healing of infected wounds can be attributed to the increased production of reactive oxygen species (ROS) and consequent damages to vascellum and tissue, resulting in a hypoxic wound environment that further exacerbates inflammation. Current clinical treatments including hyperbaric oxygen therapy and antibiotic treatment fail to provide sustained oxygenation and drug-free resistance to infection. To propose a dynamic oxygen regulation strategy, this study develops a composite hydrogel with ROS-scavenging system and oxygen-releasing microspheres in the wound dressing. The hydrogel itself reduces cellular damage by removing ROS derived from immune cells. Simultaneously, the sustained release of oxygen from microspheres improves cell survival and migration in hypoxic environments, promoting angiogenesis and collagen regeneration. The combination of ROS scavenging and oxygenation enables the wound dressing to achieve drug-free anti-infection through activating immune modulation, inhibiting the secretion of pro-inflammatory cytokines interleukin-6, and promoting tissue regeneration in both acute and infected wounds of rat skins. Thus, the composite hydrogel dressing proposed in this work shows great potential for dynamic redox regulation of infected wounds and accelerates wound healing without drugs.

Attitudes and perceptions of cancer patients and healthcare providers towards prehabilitation: A thematic synthesis.

PURPOSE: Prehabilitation, which is the process of enhancing functional capacity before undergoing surgery or other treatments, has been shown to improve cancer patients' outcomes. Patient and healthcare provider attitudes and perceptions are essential factors in the successful implementation of prehabilitation. The purpose of this systematic review is to synthesize qualitative evidence and explore the barriers and facilitators to prehabilitation implementation. METHODS: From the earliest available date to October 2023, 7 databases (PubMed, Web of Science, Cochrane Library, Embase, CINAHL, PsycINFO, and MEDLINE) were searched for a systematic review. Data were extracted, thematically analysed, and mapped onto the Capability, Opportunity, and Motivation Model of Behaviour (COM-B). The Critical Appraisal Skills Programme (CASP) tool was used to assess the quality of the studies. RESULTS: A total of 26 studies were included, involving 377 patients, 51 caregivers, and 156 healthcare providers. 16 factors were identified and mapped onto the COM-B model: reflective/automatic motivation, physical/social opportunity, physical/ psychological capability. CONCLUSIONS: Patients and healthcare provides identified a lack of reflective motivation and physical opportunities as the most significant barriers to engagement in prehabilitation. Personalized approaches, social support, and healthcare providers' engagement are key factors for prehabilitation. Future research should focus on developing effective interventions to enhance the uptake and sustainability of prehabilitation.

The relationship between fear of cancer recurrence and posttraumatic growth: a meta-analysis.

Background: Theoretically, stress is positively correlated with posttraumatic growth (PTG). However, evidence for a correlation between fear of cancer recurrence (FCR), a cancer-specific stressor, and PTG is mixed. The present study aimed to systematically investigate the overall effect size between the two and to explore moderators that may influence this relationship. Methods: From the earliest available date to October 2023, a comprehensive search was conducted in seven databases. Correlation coefficients (r) were calculated using Stata software. Publication type, continent, trauma role, gender, FCR measurements, PTG measurements, sample size, age, and time since diagnosis were used to examine moderating effects. The National Heart, Lung, and Blood Institute's (NHLBI) assessment tool was used to evaluate study quality. Results: A total of 14 studies, involving 17 samples and 3,701 participants, were included. The studies found a small association between FCR and PTG (r = 0.161, 95% CI: 0.070-0.249, p < 0.01) and large heterogeneity (I2 = 85.5%). The strength of the association varied according to the publication type and FCR measurement. Conclusion: The current review suggests a small but significant positive correlation between FCR and PTG. Future studies would benefit from exploring additional moderators and the use of standardized, validated FCR measurement tools. Systematic review registration: PROSPERO, identifier CRD42023460407.

The Real Experience of Lay Responders Performing Cardiopulmonary Resuscitation: A Synthesis of Qualitative Evidence.

Objectives: To synthesize qualitative evidence on the experience of lay responders performing cardiopulmonary resuscitation (CPR). Methods: Qualitative evidence synthesis was performed using the Thomas and Harden method. The PubMed, Cochrane Library, Web of Science, OVID Medline, Embase, CINAHL, CNKI, and WanFang databases were systematically searched. The quality of the research was assessed by the Critical Assessment Skills Program Tool (CASP). Results: A total of 5,610 studies were identified, and 9 studies were included in the analysis. Four analytical themes were generated: emotional ambivalence before CPR, psychological tolerance during CPR, perceived experience after CPR, and enhancing psychological resilience. Conclusion: Lay responders face complicated psychological experience during CPR, which may be susceptible to psychological effects such as "loss aversion," "bystander effects" and "knowledge curse." In addition to the timely retraining of CPR, lay responders should be instructed to manage psychological distress and improve psychological resilience. More importantly, the psychological sequelae may be long-lasting, requiring ongoing psychological intervention and follow-up based on valuing transdisciplinarity across endeavours.

A Gas Therapy Strategy for Intestinal Flora Regulation and Colitis Treatment by Nanogel-Based Multistage NO Delivery Microcapsules.

Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, the removal of reactive intestinal oxygen species, and regulation of the intestinal flora. However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small-molecule and biologic-based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short-chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin-17 and PI3K-Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.

The real experience with women's hysterectomy: A meta-synthesis of qualitative research evidence.

AIM: The aim of this meta-synthesis was to identify and synthesize qualitative research evaluating the real feelings, inner needs and emotional experience of women undergoing hysterectomy. DESIGN: Meta-synthesis. METHODS: The PubMed, Web of Science, Cochrane Library, CINAHL, Embase, Ovid Medline and Sino Med were systematically searched until November 2021 and updated until June 2022. Two reviewers independently extracted data into a Microsoft Excel sheet. Qualitative meta-synthesis was performed by coding relevant citations, organizing codes into descriptive themes and developing analytical themes. RESULTS: Qualitative meta-synthesis yielded three themes and nine sub-themes: comprehensive consideration before hysterectomy (a. disease factors; b. fertility factors; c. opinions of others); emotions and experience after hysterectomy (a. postoperative physical condition; b. psychological resilience to the loss of the uterus; c. changes in the couple's relationship); coping strategies (a. self-denial and avoidance; b. change of perception and self-adjustment; c. seek help from others).

Co-mutation of TP53 and TTN is Correlated with the Efficacy of Immunotherapy in Lung Squamous Cell Carcinoma.

BACKGROUND: Immunotherapy has been a promising treatment in advanced lung cancer. However, only a few patients could benefit from it. Herein, we aimed to explore mutationrelated predictive biomarkers in lung squamous cell carcinoma (LUSC), which could help develop clinical immunotherapy strategies and screen beneficial populations. METHODS: Co-occurrence and mutually exclusive analysis was conducted on the TCGA-LUSC cohort. Correlations between the gene mutation status and tumor mutation burden (TMB) levels, and neo-antigen levels were analyzed by Wilcoxon test. Kaplan-Meier method was employed to analyze the progression-free survival (PFS) of lung cancer patients with immunotherapy. Gene set enrichment analysis (GSEA) was used to investigate the functional changes affected by TP53mut/TTNmut. The immune cell infiltration landscape in co-mutation subgroups was analyzed using CIBERSORT. RESULTS: 1) TP53, TTN, CSMD3, MUC16, RYR2, LRP1B, USH2A, SYNE1, ZFHX4, FAM135B, KMT2D, and NAV3 were frequently mutated in LUSC patients. 2) TMB levels in highly mutated groups were higher than that in wild type groups. 3) There were higher neoantigen levels in mutation group compared to the wild-type group, and LUSC patients in mutation group had longer PFS. 4) TP53mut/TTNmut co-mutation group exhibited higher TMB levels and better response to immunotherapy. 5) A host of immune-related signaling pathways was inhibited in TP53mut/TTNmut subgroup. 6) There were more T follicular helper cells and NK cells were in TP53mut/TTNmut subgroup than in the WT subgroup. CONCLUSION: The LUSC patients with TP53 and TTN co-mutation had higher TMB levels and better response to immunotherapy. The TP53 and TTN co-mutation is a promising novel biomarker to assist LUSC immunotherapy evaluation.

All-Natural Immunomodulatory Bioadhesive Hydrogel Promotes Angiogenesis and Diabetic Wound Healing by Regulating Macrophage Heterogeneity.

Macrophages are highly heterogeneous and exhibit a diversity of functions and phenotypes. They can be divided into pro-inflammatory macrophages (M1) and anti-inflammatory macrophages (M2). Diabetic wounds are characterized by a prolonged inflammatory phase and difficulty in healing due to the accumulation of pro-inflammatory (M1) macrophages in the wound. Therefore, hydrogel dressings with macrophage heterogeneity regulation function hold great promise in promoting diabetic wound healing in clinical applications. However, the precise conversion of pro-inflammatory M1 to anti-inflammatory M2 macrophages by simple and biosafe approaches is still a great challenge. Here, an all-natural hydrogel with the ability to regulate macrophage heterogeneity is developed to promote angiogenesis and diabetic wound healing. The protocatechuic aldehyde hybridized collagen-based all-natural hydrogel exhibits good bioadhesive and antibacterial properties as well as reactive oxygen species scavenging ability. More importantly, the hydrogel is able to convert M1 macrophages into M2 macrophages without the need for any additional ingredients or external intervention. This simple and safe immunomodulatory approach shows great application potential for shortening the inflammatory phase of diabetic wound repair and accelerating wound healing.

LINC01315 Impairs microRNA-211-Dependent DLG3 Downregulation to Inhibit the Development of Oral Squamous Cell Carcinoma.

Recent studies have revealed that long non-coding RNAs (lncRNAs) involve in the progression of oral squamous cell carcinoma (OSCC). These lncRNAs have emerged as biomarkers or therapeutic targets for OSCC. We here aimed to investigate the role of lncRNA LINC01315 in OSCC and the related mechanisms. LINC01315 and DLG3 were determined to be poorly expressed while microRNA-211 (miR-211) was highly expressed in OSCC tissues and cells using RT-qPCR and western blot analysis. Based on the results obtained from dual-luciferase reporter gene, RIP, and FISH assays, LINC01315 was found to upregulate DLG3 expression by competitively binding to miR-211. Upon altering the expression of LINC01315, and/or miR-211 in OSCC cells with shRNA, mimic, or an inhibitor, we assessed their effects on OSCC cell proliferation, migration, invasion, and apoptosis. LINC01315 knockdown enhanced OSCC cell proliferation, migration and invasion, but dampened their apoptosis, all of which could be reversed by miR-211 inhibition. Elevation of DLG3, a target gene of miR-211, activated the Hippo signaling pathway, whereby suppressing OSCC progression in vitro. Finally, their roles in tumor growth were validated in vivo. These findings suggest that LINC01315 elevates DLG3 expression by competitively binding to miR-211, thereby suppressing OSCC progression.

Effect of Blood Pump Flow and Arteriovenous Fistula Blood Flow on the Blood Pressure and Cardiac Function in Patients Undergoing Maintenance Hemodialysis.

The effect of blood pump flow rate on the cardiac functions of hemodialysis patients with arteriovenous fistula (AVF) is largely unknown. This study aimed to investigate if blood pump flow rate (Qb) and AVF access flow rate (Qa) can affect the cardiac function of Chinese hemodialysis patients. A total of 72 patients undergoing AVF hemodialysis were included from March 2010 to June 2014 and dichotomized into the high- and low-flow groups using the medians of Qb (220 mL/min) and Qa (1000 mL/min) as the cutoffs. The cardiac function parameters were measured by ultrasound dilution technique within the first (t + 30) and the last (t - 30) 30 min of dialysis. At t + 30, Qb-high group had significantly higher systolic blood pressure (SBP) and mean arterial pressure (MAP) than Qb-low group. At t - 30, Qb-high group had higher SBP, diastolic blood pressure (DBP), and MAP than Qb-low group. Qa-high group had higher SBP, MAP, cardiac output (CO), cardiac index (CI), central blood volume (CBV), and lower peripheral resistance than Qa-low group. Multiple linear regression showed that at t - 30, Qb was positively correlated with SBP and MAP. Qa was positively correlated with CO, CI, CBV, and PR but negatively correlated with heart rate. Although Qb > 220 mL/min and Qa >1000 mL/min would elevate some parameters, the means of SBP, DBP, MAP remain within the normal range, indicating that appropriate increase in blood pump flow rate has little effect on the cardiac function of hemodialysis patients.

Effect of social support on psychological-stress-induced anxiety and depressive symptoms in patients receiving peritoneal dialysis.

OBJECTIVE: The objective of this study was to assess the association of psychological stress and social support with anxiety and depressive symptoms in peritoneal dialysis (PD) patients with end-stage renal disease (ESRD). METHODS: Eighty-one patients receiving PD were recruited. Their demographic characteristics, psychological stress, and social support were determined with a structured questionnaire, and their anxiety and depressive symptoms were assessed with the Hospital Anxiety and Depression Scale. RESULTS: Psychological stressors caused by ESRD and PD originated from five major sources, as determined by factor analysis. These included "Job and family crisis," "Worry about health and family being harmed," "Worry about daily life being restricted and physical appearance being altered," "Fear of decline in social ability," and "Fear of decline in physical function." Hierarchical linear regression analysis indicated that, after adjusting for gender, age, marital status, educational level, and duration of illness, solid social support can alleviate such symptoms.

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation.

AIM: To investigate the effects of heme oxygenase-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation (RLT) in a rat model. METHODS: BMMSCs were isolated and cultured in vitro using an adherent method, and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs. A rat acute rejection model following 50% RLT was established using a two-cuff technique. Recipients were divided into three groups based on the treatment received: normal saline (NS), BMMSCs and HO-1/BMMSCs. Liver function was examined at six time points. The levels of endothelin-1 (ET-1), endothelial nitric-oxide synthase (eNOS), inducible nitric-oxide synthase (iNOS), nitric oxide (NO), and hyaluronic acid (HA) were detected using an enzyme-linked immunosorbent assay. The portal vein pressure (PVP) was detected by Power Lab ML880. The expressions of ET-1, iNOS, eNOS, and von Willebrand factor (vWF) protein in the transplanted liver were detected using immunohistochemistry and Western blotting. ATPase in the transplanted liver was detected by chemical colorimetry, and the ultrastructural changes were observed under a transmission electron microscope. RESULTS: HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver, and improve the liver function of rats following 50% RLT, with statistically significant differences compared with those of the NS group and BMMSCs group (P < 0.05). In term of the microcirculation of hepatic sinusoids: The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group (P < 0.01); HO-1/BMMSCs could inhibit the expressions of ET-1 and iNOS, increase the expressions of eNOS and inhibit amounts of NO production, and maintain the equilibrium of ET-1/NO (P < 0.05); and HO-1/BMMSCs increased the expression of vWF in hepatic sinusoidal endothelial cells (SECs), and promoted the degradation of HA, compared with those of the NS group and BMMSCs group (P < 0.05). In term of the energy metabolism of the transplanted liver, HO-1/BMMSCs repaired the damaged mitochondria, and improved the activity of mitochondrial aspartate aminotransferase (ASTm) and ATPase, compared with the other two groups (P <0.05). CONCLUSION: HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly, and recover the energy metabolism of damaged hepatocytes in rats following RLT, thus protecting the transplanted liver.

Osteogenesis of bone marrow mesenchymal stem cells on strontium-substituted nano-hydroxyapatite coated roughened titanium surfaces.

OBJECTIVE: To investigate osteogenesis of bone marrow mesenchymal stem cells (BMSCs) on strontium-substituted nano-hydroxyapatite (Sr-HA) coated roughened titanium surfaces. METHODS: Sr-HA coating and HA coating were fabricated on roughened titanium surfaces by electrochemical deposition technique and characterized by field emission scanning electron microscope (FESM). BMSCs were cultured on Sr-HA coating, HA coating and roughened titanium surfaces respectively. Cell proliferation, alkaline phosphatase (ALP) activity, mineralized nodules formation and cell osteocalcin (OC) secretion were measured. RESULTS: Electrochemically deposited Sr-HA coating and HA coating had no effect on the proliferation of BMSCs and demonstrated that the materials have a good biocompatibility. BMSCs cultured on Sr-HA coating showed increased alkaline phosphatase activity, mineralized nodules formation, and cell OC secretion compared with the other two groups. Cells cultured on HA coating also showed increased biological activity compared with the roughened group. CONCLUSION: Sr-HA coated titanium surfaces by electrochemical deposition can promote osteogenesis of BMSCs in vitro and have the potential to shorten bone healing period and enhance implant osseointegration.

Influence of cyclic loading on the fracture toughness and load bearing capacities of all-ceramic crowns.

The purpose of this study was to investigate how cyclic loading influenced the fracture toughness of hot-press lithium disilicate and zirconia core materials and whether there was an increase in the propensity for crown failure. Two types of all-ceramic crowns including the IPS e.max Press system (n=24) and the Lava zirconia system (n=24), were selected. Sectioned specimens were subjected to cyclic loading with the maximum magnitude of 200 N (R=0.1) until two million cycles. The material properties including Young's modulus (E) and hardness (H) and the fracture toughness (KIC) of the core materials were evaluated using indentation methods (n=12 each). The load-bearing capacities of the specimens were examined by means of monotonic load to fracture (n=12 each). It was found that the material properties, including E, H and KIC, of the two types of dental ceramics, were reduced. Statistical analysis indicated that there were no significant influences of fatigue loading on material properties E and H for both types of dental ceramics or KIC for zirconia, while for the IPS e.max Press core, KIC, which was parallel to the direction of the lithium disilicate crystals, was significantly reduced (P=0.001). A conclusion was drawn that zirconia possesses high mechanical reliability and sustainable capacity to resist fatigue loading, while fatigue loading remarkably degraded the anisotropic mechanical behaviour of hot-press lithium disilicate ceramics.

[The disinfecting effect of ozone on four kinds of bacteria].

PURPOSE: To evaluate the disinfecting effect of ozone on 4 kinds of bacteria: Staphylococcus aureus, Streptococcus mutans, Staphylococcus epidermidis and Streptococcus pneumoniae. METHODS: The concentration of ozone that was transmitted by ozone generator at different time was determined by using iodine titrimetric method. According to the bactericidal assay of quantitative vehicle, the bacteria on the ozonized vehicles and unozonized vehicles was washed, 50 microl eluant was seeded on the TSA plates. The TSA plates were put into the anaerobiotic incubator (90% N(2),10% CO(2),37 degrees centigrade). After 24 to 48 hours, the CFU on the plate was counted.The data was analyzed by one-way ANOVA with SAS 6.12 software package. RESULTS: The sterilization effect depended on the ozone concentration and the treatment time. When the 4 kinds of bacteria were treated with 2.73 mg/L ozone for 45 minutes, there was no bacteria alive. CONCLUSIONS: Ozone has obvious disinfecting effect on the 4 kinds of bacteria and the effect is correlated with the concentration of ozone.