Disinfection Byproducts of Haloacetaldehydes Disrupt Hepatic Lipid Metabolism and Induce Lipotoxicity in High-Fat Culture Conditions.

Unhealthy lifestyles, obesity, and environmental pollutants are strongly correlated with the development of nonalcoholic fatty liver disease (NAFLD). Haloacetaldehyde-associated disinfection byproducts (HAL-DBPs) at various multiples of concentrations found in finished drinking water together with high-fat (HF) were examined to gauge their mixed effects on hepatic lipid metabolism. Using new alternative methods (NAMs), studying effects in human cells in vitro for risk assessment, we investigated the combined effects of HF and HAL-DBPs on hepatic lipid metabolism and lipotoxicity in immortalized LO-2 human hepatocytes. Coexposure of HAL-DBPs at various multiples of environmental exposure levels with HF increased the levels of triglycerides, interfered with de novo lipogenesis, enhanced fatty acid oxidation, and inhibited the secretion of very low-density lipoproteins. Lipid accumulation caused by the coexposure of HAL-DBPs and HF also resulted in more severe lipotoxicity in these cells. Our results using an in vitro NAM-based method provide novel insights into metabolic reprogramming in hepatocytes due to coexposure of HF and HAL-DBPs and strongly suggest that the risk of NAFLD in sensitive populations due to HAL-DBPs and poor lifestyle deserves further investigation both with laboratory and epidemiological tools. We also discuss how results from our studies could be used in health risk assessments for HAL-DBPs.

Perspectives of clinical nurse educators on competency-based nursing teaching in blended learning environments during nursing internship: A descriptive qualitative study.

AIM: To investigate the perspectives of clinical nurse educators regarding the challenges and essential elements of teaching competence in blended learning environments during nursing internships to inform the development of a competency-based teaching model. BACKGROUND: Competency-based teaching and blended learning play important roles in enhancing the learning experience of nursing internship trainees. Internship trainees refer to nursing students undergoing supervised practical training in clinical settings. However, clinical nurse educators frequently encounter challenges in acquiring the necessary competence for successful implementation of blended learning strategies. DESIGN: A descriptive qualitative study. METHODS: This study used semi-structured interviews with 11 certified nurse educators (CNEs) from diverse clinical disciplines in a tertiary hospital in China. Purposive sampling ensured diversity across key characteristics. Ethical approval was obtained and interviews were digitally recorded, transcribed and analyzed thematically. Theoretical saturation guided data collection, with precise measures taken to ensure confidentiality and anonymity. Thematic analysis, employing a constant comparison technique, systematically identified various themes related to blended teaching competence. This approach provided valuable insights into CNEs' perspectives and practices. The analysis involved theoretical sampling, line-by-line coding and comparative evaluation with supporting text materials. RESULTS: The in-depth analysis of teaching competence among clinical nurse educators in blended learning settings during nurse internships revealed five key themes: professionalism, teaching literacy, subject expertise, information literacy and interpersonal communication. CONCLUSION: These themes recognized clinical nurse educators' perspectives towards establishing a competency-based nursing teaching model for a blended learning environment for nurse internships. Moreover, these perspectives are also crucial in enhancing teaching literacy through effective instructional methods, engagement strategies and the promotion of critical thinking skills. Identifying these themes contributes to efforts to improve teaching effectiveness and enhance learning outcomes for internship trainees in a blended learning context.

Intestinal microbiota imbalance resulted by anti-Toxoplasma gondii immune responses aggravate gut and brain injury.

BACKGROUND: Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers. Therefore, identifying imbalanced probiotics during infection and restoring their equilibrium can regulate the balance of gut microbiota metabolites, thereby alleviating tissue damage. METHODS: Vimentin gene knockout (vim-/-) mice were employed as an immunocompromised model to evaluate the influence of host immune responses on gut microbiota balance during T. gondii infection. Behavioral experiments were performed to assess changes in cognitive levels and depressive tendencies between chronically infected vim-/- and wild-type (WT) mice. Fecal samples were subjected to 16S ribosomal RNA (rRNA) sequencing, and serum metabolites were analyzed to identify potential gut probiotics and their metabolites for the treatment of T. gondii infection. RESULTS: Compared to the immunocompetent WT sv129 mice, the immunocompromised mice exhibited lower levels of neuronal apoptosis and fewer neurobehavioral abnormalities during chronic infection. 16S rRNA sequencing revealed a significant decrease in the abundance of probiotics, including several species of Lactobacillus, in WT mice. Restoring this balance through the administration of Lactobacillus murinus and Lactobacillus gasseri significantly suppressed the T. gondii burden in the intestine, liver, and brain. Moreover, transplantation of these two Lactobacillus spp. significantly improved intestinal barrier damage and alleviated inflammation and neuronal apoptosis in the central nervous system. Metabolite detection studies revealed that the levels of various Lactobacillus-related metabolites, including indole-3-lactic acid (ILA) in serum, decreased significantly after T. gondii infection. We confirmed that L. gasseri secreted much more ILA than L. murinus. Notably, ILA can activate the aromatic hydrocarbon receptor signaling pathway in intestinal epithelial cells, promoting the activation of CD8+ T cells and the secretion of interferon-gamma. CONCLUSION: Our study revealed that host immune responses against T. gondii infection severely disrupted the balance of gut microbiota, resulting in intestinal and brain damage. Lactobacillus spp. play a crucial role in immune regulation, and the metabolite ILA is a promising therapeutic compound for efficient and safe treatment of T. gondii infection.

Risk factors for endoscopic postoperative recurrence in patients with Crohn's Disease: a protocol for systematic review and meta-analysis.

BACKGROUND: Crohn's disease (CD) is a chronic condition characterized by a high recurrence rate after surgery, which seriously affects the quality of life of patients. Many studies have explored the risk factors for the recurrence of CD after surgery, there is a lack of meta-analysis focusing on endoscopic postoperative recurrence (ePOR) as a clinical outcome. Therefore, this paper aims to identify the risk factors for ePOR in CD patients through systematic review and meta-analysis. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for related literature from inception to 17th October 2023. Two researchers independently screened the literature and extracted information. Data analysis was performed using Stata18.0. RESULTS: Twenty-three papers were included, with 5 case-control studies and 18 cohort studies. The National Institutes of Health quality assessment tool rated 17 studies as good and 6 studies as fair. The sample size of the 23 studies ranged from 40 to 346, and the number of patients with ePOR ranged from 23 to 169. The results of multivariate meta-analysis showed that smoking [OR = 2.06, 95% CI (1.65, 2.57), P = 0.0001], previous ileocolonic resection [OR = 1.71, 95% CI (1.23, 2.38), P = 0.002], disease localization at ileocolic resection [OR = 2.68, 95% CI (1.38, 5.22), P = 0.004], perianal disease [OR = 1.47, 95% CI (1.07, 2.03), P = 0.017], and anastomotic scattered ulcer [OR = 3.39, 95% CI (1.83, 6.28), P = 0.001] were risk factors for ePOR in CD patients. Postoperative prophylactic medication [OR = 0.53, 95% CI (0.38,0.75), P = 0.0001] was a protective factor for ePOR in CD patients. CONCLUSIONS: This systematic review identified multiple factors for ePOR in CD patients, as well as a protective factor. However, the number of articles included was limited. More high-quality clinical studies are required to further validate the conclusions. TRIAL REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023483671).

Exploration of the Long-term Prognostic Value of Cholangioscopy Combined with Minimally Invasive Abdominal Surgery in Reducing the Possibility of Stone Recurrence in Elderly Patients with Gallstones.

Objective: To observe the effect of cholangioscopy (CS) combined with minimally invasive abdominal surgery on prognosis stone recurrence in elderly patients (≥60 years old) with gallstones (GS). Methods: One hundred and fourteen GS patients admitted to The First Hospital of Nanchang between August 2018 and December 2021 were selected for the study, and they were randomly divided into the control group (n=57) and the observation group (n=57). The control group was treated with open surgery, while the observation group was given CS combined with minimally invasive stone removal surgery. Inter-group comparisons were made regarding operation time, intraoperative blood loss, postoperative intestinal function recovery, hospitalization time, clinical efficacy, and postoperative complication rate. Pain intensities before and, 4, 24, 48, and 72 hours after surgery were assessed using the Visual Analogue Score. After a 1-year post-discharge follow-up, the stone recurrence rate was counted, and the Gastrointestinal Quality-of-Life Index evaluated the quality of life. Results: There was no difference in operation time between the two groups (P > .05), but intraoperative blood loss, recovery time of intestinal function, hospitalization time, and complication rate were all lower in the observation group than in the control group (P < .05). In addition, the clinical efficacy of the observation group was better, and postoperative pain was lower (P < .05). In the prognostic follow-up, it was seen that the observation group had a lower stone recurrence rate (3.51%) and better quality of life (P < .05). Conclusions: CS combined with minimally invasive abdominal surgery is effective and safe in treating patients with GS and can validly reduce the prognosis risk of recurrent stones in patients, which deserves popularization in clinical use.

Discovery of novel CXCR4 inhibitors for the treatment of inflammation by virtual screening and biological evaluation.

C-X-C chemokine receptor type 4 (CXCR4) exerts considerable influence on the pathogenesis of inflammatory disorders and offers a potent avenue for drug intervention. This research utilizes a hybrid virtual screening methodology constructed using computer-aided drug design to discover novel CXCR4 inhibitors for the treatment of inflammation. First, a compound library was screened by Lipinski's five rules and adsorption, distribution, metabolism, excretion and toxicity properties. Second, the HypoGen algorithm was used in constructing a 3D-QSAR pharmacophore model and verify it layer by layer, and the obtained optimal pharmacophore 1 (Hypo 1) was used as a 3D query for compound screening. Then, hit compounds were obtained through molecular docking (Libdock and CDOCKER). The toxicity of the compounds to MDA-MB-231 cells was evaluated in vitro, and their binding affinity to the target was evaluated according to how they compete with 12G5 antibody for CXCR4 on the surfaces of the MDA-MB-231 cells. Compound Hit14 showed the strongest binding affinity among the hit compounds and inhibited cell migration and invasion in Matrigel invasion and wound healing assay at a concentration of 100 nM, demonstrating a better effect than AMD3100. Western Blot experiments further showed that Hit14 blocked the CXCR4/CXCL12-mediated phosphorylation of Akt. Meanwhile, cellular thermal displacement assay analysis showed that CXCR4 protein bound to Hit14 had high thermal stability. Finally, through in vivo experiments, we found that Hit14 inhibited mouse ear inflammation and reduced ear swelling and damage. Therefore, Hit14 is a promising drug for the further development of CXCR4 inhibitors for inflammation treatment.

RP11-874 J12.4 promotes erlotinib resistance in non-small cell lung cancer via increasing AXL expression.

EGFR tyrosine kinase inhibitor (TKI) resistance is a major challenge for EGFR-mutant non-small cell lung cancer (NSCLC) treatment. Our previous work revealed that overexpression of AXL promoted EGFR-TKI resistance through epithelial-mesenchymal transition (EMT) in a subset of NSCLC patients. Compared with erlotinib resistant and sensitive cells, RP11-874 J12.4 was upregulated in erlotinib-resistant NSCLC cells (HCC827-ER3). Interestingly, the expression of RP11-874 J12.4 positively correlated with AXL. Besides, RP11-874 J12.4 promotes NSCLC cell proliferation and metastasis in vitro. Mechanistically, RP11-874 J12.4 promoted AXL expression through sponge with miR-34a-5p, which was reported to inhibit the translation of AXL mRNA. Meanwhile, the expression of RP11-874 J12.4 in lung cancer tumors were higher than the adjacent tissue, and those patients with high expression of RP11-874 J12.4 showed a poor prognosis in clinical. High expression of RP11-874 J12.4 might be a biomarker for NSCLC patients with erlotinib resistance. These findings reveal a novel insight into the mechanism of erlotinib resistance in NSCLC, and it might be a promising target for the diagnosis and treatment of NSCLC.

Formation of persistent free radicals from epigallocatechin Gallate in tea processing and their implications on DNA damage and cell cytotoxicity.

Tea is widely consumed in both beverages and food. Epigallocatechin gallate (EGCG) is the most crucial active ingredient in tea. Currently, knowledges on transformation processes of EGCG during tea processing are lacking. Understanding the chemical reactions of EGCG and its products during tea processing is important for assessing the safety of tea-containing food. Here, we revealed the formation of persistent free radicals (PFRs) from EGCG under the influence of heating and light irradiation, which was substantiated with evidence. These PFRs exhibited stability for >30 min in simulated gastric fluid. Furthermore, we observed potential effects of these PFRs on DNA damage and cell cytotoxicity in vitro. By combining electron paramagnetic resonance spectrometer with Fourier transform ion cyclotron resonance mass spectrometry, we elucidated the pathways involved in free radical formation. These findings are expected to contribute to a comprehensive understanding of free radical chemistry in tea-containing food.

Haloacetamides disinfection by-products, a potential risk factor for nonalcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by abnormal lipid deposition, with oxidative stress being a risk factor in its onset and progression. Haloacetamides (HAcAms), as unregulated disinfection by-products in drinking water, may alter the incidence and severity of NAFLD through the production of oxidative stress. We explored whether HAcAms at 1, 10, and 100-fold concentrations in Shanghai drinking water perturbed lipid metabolism in normal human liver LO-2 cells. CRISPR/Cas9 was used to construct a LO-2 line with stable NRF2 knock-down (NRF2-KD) to investigate the mechanism underlying abnormal lipid accumulation and hepatocyte damage caused by mixed exposure to HAcAms. At 100-fold real-world concentration, HAcAms caused lipid deposition and increased triglyceride accumulation in LO-2 cells, consistent with altered de novo lipogenesis. Differences in responses to HAcAms in normal and NRF2-KD LO-2 cells indicated that HAcAms caused hepatocyte lipid deposition and triglyceride accumulation by activation of the NRF2/PPARγ pathway and aggravated liver cell toxicity by inducing ferroptosis. These results indicate that HAcAms are important risk factors for NAFLD. Further observations and verifications of the effect of HAcAms on NAFLD in the population are warranted in the future.

Atmospheric emissions of hexachlorobutadiene in fine particulate matter from industrial sources.

Hexachlorobutadiene (HCBD) is a concerning chemical that is included in the United States Toxic Substances Control Act, and the Stockholm Convention. Knowledge of the sources of HCBD is insufficient and is pivotal for accurate inventory and implementing global action. In this study, unintentional HCBD release and source emission factors of 121 full-scale industrial plants from 12 industries are investigated. Secondary copper smelting, electric arc furnace steelmaking, and hazardous waste incineration show potential for large emission reductions, which are found of high HCBD emission concentrations of > 20 ng/g in fine particulate matter in this study. The highest HCBD emission concentration is observed for the secondary copper smelting industry (average: 1380 ng/g). Source emission factors of HCBD for the 12 industries range from 0.008 kg/t for coal fire power plants to 0.680 kg/t for secondary lead smelting, from which an estimation of approximately 8452.8 g HCBD emissions annually worldwide achieved. The carcinogenic risks caused by HCBD emissions from countries and regions with intensive 12 industrial sources are 1.0-80 times higher than that without these industries. These results will be useful for formulating effective strategies of HCBD control.

TIPRL, a Potential Double-edge Molecule to be Targeted and Re-targeted Toward Cancer.

The target of rapamycin (TOR) proteins exhibits phylogenetic conservation across various species, ranging from yeast to humans, and are classified as members of the phosphatidylinositol kinase (PIK)-related kinase family. Multiple serine/threonine (Ser/Thr) protein phosphatases (PP)2A, PP4, and PP6, have been recognized as constituents of the TOR signaling pathway in mammalian cells. The protein known as TOR signaling pathway regulator-like (TIPRL) functions as a regulatory agent by impeding the activity of the catalytic subunits of PP2A. Various cellular contexts have been postulated for TIPRL, encompassing the regulation of mechanistic target of rapamycin (mTOR) signaling, inhibition of apoptosis and biogenesis, and recycling of PP2A. According to reports, there has been an observed increase in TIPRL levels in several types of carcinomas, such as non-small-cell lung carcinoma (NSCLC) and hepatocellular carcinomas (HCC). This review aims to comprehensively examine the significance of the Tor pathway in regulating apoptosis and proliferation of cancer cells, with a specific focus on the role of TOR signaling and TIPRL in cancer.

Data-Driven Engineering of Phages with Tunable Capsule Tropism for Klebsiella pneumoniae.

Klebsiella pneumoniae, a major clinical pathogen known for causing severe infections, is attracting heightened attention due to its escalating antibiotic resistance. Phages are emerging as a promising alternative to antibiotics; however, their specificity to particular hosts often restricts their use. In this study, a collection of 114 phages is obtained and subjected to analysis against 238 clinical K. pneumoniae strains, revealing a spectrum of lytic behaviors. A correlation between putative tail protein clusters and lysis patterns leads to the discovery of six receptor-binding protein (RBP) clusters that determine host capsule tropism. Significantly, RBPs with cross-capsular lysis capabilities are identified. The newly-identified RBPs provide a toolbox for customizing phages to target diverse capsular types. Building on the toolbox, the engineered phages with altered RBPs successfully shifted and broadened their host capsule tropism, setting the stage for tunable phage that offer a precise and flexible solution to combat K. pneumoniae infections.

Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.

Effect of shenmai injection on anthracycline-induced cardiotoxicity: A systematic review and meta-analysis.

OBJECTIVE: Shenmai injection is a classic herbal prescription, and is often recommended for the treatment of anthracycline-induced cardiotoxicity. However, the efficacy and safety of Shenmai injection for the treatment of anthracycline-induced cardiotoxicity have not been reported. MATERIALS AND METHODS: We conducted a comprehensive search of eight literature databases and two clinical trial registries, retrieving all randomized controlled trials (RCTs) related to the treatment of anthracycline-induced cardiotoxicity with Shenmai injection from the establishment of the databases to July 1, 2023. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. The GRADE pro3.6.1 software was utilized for assessing the quality of evidence. RESULTS: A total of 16 RCTs including 2140 patients were included in this study. Meta-analysis showed that Shenmai injection had an advantage in improving ST-T segment changes (RR = 0.28; 95 % CI, 0.20 to 0.39; P < 0.0001) (P < 0.01), creatine kinase isoenzyme (SMD = -3.49; 95 % CI, -5.24 to -1.74; P < 0.0001), Prolonged QT interval (RR = 0.46; 95 % CI, 0.28 to 0.75; P = 0.0018), Low QRS Voltage (RR = 0.44; 95 % CI, 0.27 to 0.71; P = 0.0007), sinus tachycardia (RR = 0.41; 95 % CI, 0.28 to 0.60; P < 0.0001), atrial premature beats (RR = 0.55; 95 % CI, 0.35 to 0.87; P = 0.01), Premature Ventricular Contractions (RR = 0.39; 95 % CI, 0.26 to 0.59; P < 0.0001) and creatine kinase (SMD = -1.43; 95 % CI, -2.57 to -0.29; P < 0.0001) in patients with anthracycline-induced cardiotoxicity. advantage, which was supported by sensitivity analyses, but not in improving left ventricular ejection fraction (MD = 16.01; 95 % CI, -3.10 to 35.12; P = 0.10) and atrioventricular block (RR = 0.49; 95 % CI, 0.24 to 1.03; P = 0.06). The literature included in the study did not refer to data regarding the safety aspects of Shenmai injection, so we do not yet know the safety of Shenmai injection. The results of subgroup analyses suggested that heterogeneity was not related to the administered dose and chemotherapy regimen. The publication bias test showed no publication bias. The quality of evidence for the results ranged from "very low" to "moderate." CONCLUSION: This study suggests that Shenmai injection is effective in treating anthracycline-induced cardiotoxicity and is a potential treatment for anthracycline-induced cardiotoxicity. However, due to the poor methodological quality of the included RCTs, we recommend rigorous, high-quality, large-sample trials to confirm our findings.

Zeaxanthin dipalmitate-enriched wolfberry extract improves vision in a mouse model of photoreceptor degeneration.

Zeaxanthin dipalmitate (ZD) is a chemical extracted from wolfberry that protects degenerated photoreceptors in mouse retina. However, the pure ZD is expensive and hard to produce. In this study, we developed a method to enrich ZD from wolfberry on a production line and examined whether it may also protect the degenerated mouse retina. The ZD-enriched wolfberry extract (ZDE) was extracted from wolfberry by organic solvent method, and the concentration of ZD was identified by HPLC. The adult C57BL/6 mice were treated with ZDE or solvent by daily gavage for 2 weeks, at the end of the first week the animals were intraperitoneally injected with N-methyl-N-nitrosourea to induce photoreceptor degeneration. Then optomotor, electroretinogram, and immunostaining were used to test the visual behavior, retinal light responses, and structure. The final ZDE product contained ~30mg/g ZD, which was over 9 times higher than that from the dry fruit of wolfberry. Feeding degenerated mice with ZDE significantly improved the survival of photoreceptors, enhanced the retinal light responses and the visual acuity. Therefore, our ZDE product successfully alleviated retinal morphological and functional degeneration in mouse retina, which may provide a basis for further animal studies for possible applying ZDE as a supplement to treat degenerated photoreceptor in the clinic.

Population-based cohort study of Toxoplasma gondii P22 antibody positivity correlation with anxiety.

BACKGROUND: Accumulating evidence suggests that latent infection with Toxoplasma gondii (T. gondii) is associated with a variety of neuropsychiatric and behavioral conditions. This research aims to explore the potential correlation between T. gondii antibody positivity and neuropsychiatric disorders through a comprehensive prospective cohort study. METHODS: The cohort study utilized the UK Biobank database to recruit 8814 individuals with no prior diagnosis of neuropsychiatric disorders. Cox proportional hazards models were employed to investigate the associations between T. gondii P22 antibody seropositivity (P22+) and the development of various types of neuropsychiatric disorders. RESULTS: Of the population, 14.65 % tested positive for T. gondii P22 antibody. The presence of T. gondii P22 antibody showed a slight inverse association with epilepsy (HR: 0.28; 95 % CI: 0.10-0.77), while it was positively associated with an increased risk of developing anxiety disorders (HR: 1.38; 95 % CI: 1.04-1.83). LIMITATIONS: The study sample consisted mostly of white British individuals aged 40 to 69 years old. Although we adjusted for potential confounders, there may be other unmeasured and residual confounding factors that could have influenced our reported associations. CONCLUSIONS: The findings suggested an increased risk of anxiety and potential evidence of epilepsy associated with T. gondii P22+. However, our analysis did not reveal an increased risk of several other neuropsychiatric conditions including Alzheimer's disease, dementia, substance abuse disorders, depression, and neurodegenerative disorders, associated with P22 antibody seropositivity.

HuoXueTongFu formula induces M2c macrophages via the MerTK/PI3K/AKT pathway to eliminate NETs in intraperitoneal adhesion in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: HuoXueTongFu Formula (HXTF) is a traditional Chinese herbal formula that has been used as a supplement and alternative therapy for intraperitoneal adhesion (IA). However, its specific mechanism of action has not been fully understood. AIM OF THE STUDY: In surgery, IA presents an inevitable challenge, significantly impacting patients' physical and mental well-being and increasing the financial burden. Our previous research has confirmed the preventive effects of HXTF on IA formation. However, the precise mechanism of its action still needs to be understood. METHODS: In this study, the IA model was successfully established by using the Ischemic buttons and treated with HXTF for one week with or without Mer Tyrosine Kinase (MerTK) inhibitor. We evaluated the pharmacodynamic effect of HXTF on IA mice. The MerTK/phosphoinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway-associated proteins were detected by Western blotting. Neutrophil extracellular traps (NETs) were detected by immunofluorescence. Macrophage phenotype was assessed by immunohistochemistry and flow cytometry. Inflammatory cytokines were detected by Real Time Quantitative PCR and Western blotting. RESULTS: HXTF reduced inflammatory response and alleviated IA. HXTF significantly enhanced MerTK expression, increased the number of M2c macrophages, and decreased the formation of NETs. In addition, the MerTK/PI3K/AKT pathway was significantly activated by HXTF. However, after using MerTK inhibitors, the role of HXTF in inducing M2c macrophage through activation of the PI3K/AKT pathway was suppressed and there was no inhibitory effect on NETs formation and inflammatory responses, resulting in diminished inhibition of adhesion. CONCLUSION: HXTF may improve IA by activating the MerTK/PI3K/AKT pathway to induce M2c polarization, which removes excess NETs and attenuates the inflammatory response.

Development and validation of a prediction model for postoperative pneumonia in patients who received spinal surgery: A retrospective study.

Objectives: To develop and validate a risk prediction model by identifying the preoperative factors associated with an increased risk of pneumonia after spinal surgery. Methods: This study included patients with spinal disease from two hospitals between January 2021 and June 2023. The patients were divided into the training and validation sets, which were categorized as postoperative pneumonia (POP) or non-POP, respectively. This study identified the independent risk variables for POP using a multivariate logistic regression analysis. A nomogram prediction model was developed and validated using risk factors, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) to assess predictive performance. Results: Following exclusion, 2223 patients from Changzheng Hospital were enrolled in the training set and 357 patients from the No. 905 Hospital of PLA Navy were enrolled in the validation set. Univariate and multivariate logistic regression analyses revealed that operation time, American Society of Anesthesiologists (ASA) grade, smoking, non-wearing of medical masks, lack of preoperative respiratory training, chronic obstructive pulmonary disease (COPD), underlying diseases, and spinal section were risk factors for POP development in patients with spinal diseases. The area under the ROC curve of the training set was 0.950, whereas that of the validation set was 0.879. The model calibration curves demonstrated good agreement, and the DCA indicated a high expected net benefit value. Conclusion: The POP risk prediction model has high accuracy and efficiency in predicting POP in patients with spinal diseases. POP development is influenced by factors such as operation length, ASA grade, smoking, non-wearing of medical masks, lack of preoperative respiratory training, COPD, underlying diseases, and lumbar surgery.

Exploring work readiness: A qualitative descriptive study of self-perceptions among new graduate nurses.

Background: Reduced work readiness is associated with elevated turnover rates, necessitating efforts to enhance the positive work readiness of newly graduated nurses to alleviate the shortage in the nursing workforce. Research into the work readiness of recent nursing graduates in China is still in its infancy. Most studies employ quantitative research methods, and further exploration of the self-perception of work readiness among new nurses in China is required. Objectives: This study aimed to investigate genuine experiences and self-perceptions of work readiness among new graduate nurses. Design: A qualitative descriptive study. Methods: Sixteen new nurses from a provincial tertiary hospital in China were included in this study, which adhered to the consolidated criteria for reporting qualitative research (COREQ) checklist for reporting. The data collection process involved conducting semi-structured interviews from September to October 2021. Inductive content analysis was employed to analyze the interview data. Results: The study identified four themes encompassing new nurses' real-life experiences and self-perceptions of work readiness: psychological stress, emotional conflict, empathy fatigue, and ethical dilemmas. Psychological stress comprised three subthemes: knowledge and skill deficits, communication barriers, and fear. Empathy fatigue was primarily characterized by psychological and physical symptoms. Ethical dilemmas involved conflicts over differences in values and between clinical reality and standardized nursing practice. Conclusion: Drawing from the self-perceptions of work readiness among new nurses found in this study, nursing administrators and educators must enhance the existing transition support program for new nurses. Additionally, the establishment of individualized training programs is recommended to further improve the work readiness of new nurses.

Toxoplasma gondii infection positively associated with schizophrenia: Evidences from UK Biobank cohort and case-controlled studies.

Toxoplasma gondii (T. gondii) is an opportunistic pathogen affecting about 1/3 of world population. While often asymptomatic in immunocompetent individuals, it can lead to severe toxoplasmosis in immunocompromised patients. Recent research has unveiled a potential link between T. gondii infection and neuropsychiatric diseases. We implemented both a cohort study and a case control study to further identify this association. In the cohort study, we analyzed data from the UK Biobank database, which included 8814 individuals tested for T. gondii SAG1 antibodies and free of neuropsychiatric disorders at baseline. Among them, 22.52% (n = 1985) tested positive for SAG1 antibody. Over an average follow-up period of 12.26 years, Cox proportional hazards models and logistic regression analysis revealed a significant association between the SAG1 seropositivity at baseline and the incidence of schizophrenia (HR: 5.89; 95% CI: 1.69-20.53). In our case-control study, 239 patients diagnosed with schizophrenia and 455 healthy individuals were involved. Using the modified agglutination test (MAT) to detect T. gondii antibodies, logistic regression analysis showed a higher prevalence of T. gondii infection among schizophrenia patients (10.04%) compared to healthy controls (3.74%). T. gondii infection emerged as a significant risk factor for schizophrenia (OR: 3.33; 95% CI: 1.68-6.61). However, our investigations did not reveal a robust association between T. gondii infection and other neuropsychiatric conditions, including Alzheimer's disease, dementia, anxiety, depression, neurodegenerative disorders, and peripheral neurological disorders such as neurological and plexus disorders.