Neutrophil extracellular traps as a unique target in the treatment of inflammatory pain.

Pain is a widespread motivation for seeking healthcare and stands as a substantial global public health concern. Despite comprehensive investigations into the mechanisms of pain sensitization induced by inflammation, efficacious treatments options remain scarce. Neutrophil extracellular traps (NETs) have been associated with the progression and tissue damage of diverse inflammatory diseases. This study aims to explore the impact of NETs on the progression of inflammatory pain and explore potential therapeutic approaches. Initially, we observed neutrophil infiltration and the formation of NETs in the left hind paw of mice with inflammatory pain induced by complete Freund's adjuvant (CFA). Furthermore, we employed the peptidyl arginine deiminase 4 (PAD4) inhibitor Cl-amidine (diluted at 50 mg/kg in saline, administered via tail vein injection once daily for three days) to impede NETs formation and administered DNase1 (diluted at 10 mg/kg in saline, once daily for three days) to break down NETs. We investigated the pathological importance of peripheral NETs formation in inflammatory pain and its influence on the activation of spinal dorsal horn microglia. The findings indicate that neutrophils infiltrating locally generate NETs, leading to an increased release of inflammatory mediators that worsen peripheral inflammatory reactions. Consequently, this results in the transmission of more harmful peripheral stimuli to the spinal cord, triggering microglial activation and NF-κB phosphorylation, thereby escalating neuroinflammation and fostering pain sensitization. Suppression of peripheral NETs can mitigate peripheral inflammation in mice with inflammatory pain, reverse mechanical and thermal hypersensitivity by suppressing microglial activation in the spinal cord, ultimately diminishing inflammatory pain. In conclusion, these discoveries propose that obstructing or intervening with NETs introduces a novel therapeutic avenue for addressing inflammatory pain.

Single-cell atlas reveals the immunosuppressive microenvironment and Treg cells landscapes in recurrent Glioblastoma.

Patients diagnosed with glioblastoma (GBM) have the most aggressive tumor progression and lethal recurrence. Research on the immune microenvironment landscape of tumor and cerebrospinal fluid (CSF) is limited. At the single-cell level, we aim to reveal the recurrent immune microenvironment of GBM and the potential CSF biomarkers and compare tumor locations. We collected four clinical samples from two patients: malignant samples from one recurrent GBM patient and non-malignant samples from a patient with brain tumor. We performed single-cell RNA sequencing (scRNA-seq) to reveal the immune landscape of recurrent GBM and CSF. T cells were enriched in the malignant tumors, while Treg cells were predominately found in malignant CSF, which indicated an inhibitory microenvironment in recurrent GBM. Moreover, macrophages and neutrophils were significantly enriched in malignant CSF. This indicates that they an important role in GBM progression. S100A9, extensively expressed in malignant CSF, is a promising biomarker for GBM diagnosis and recurrence. Our study reveals GBM's recurrent immune microenvironment after chemoradiotherapy and compares malignant and non-malignant CSF samples. We provide novel targets and confirm the promise of liquid CSF biopsy for patients with GBM.

Study on the correlation between serum indole-3-propionic acid levels and the progression and prognosis of acute ischemic stroke.

OBJECTIVE: This study aimed to explore the correlation between the serum level of indole-3-propionic acid (IPA) and the progression and prognosis of acute cerebral infarction (ACI). METHODS: This study enrolled 197 patients with ACI, and 53 participants from a community-based stroke screening program during the same period were included as the control group. The patients with ACI were divided into quartiles of serum IPA. A logistic regression model was used for comparison. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of the IPA. RESULTS: Compared with the healthy control group, the ACI group had lower serum IPA (P < 0.05). The serum IPA was an independent factor for acute ischemic stroke (OR=0.992, 95% CI: 0.984-0.999, P=0.035). The serum IPA was lower in patients with progressive stroke or poor prognosis than in patients with stable stroke or good prognosis (P < 0.05). Patients with ACI with low serum IPA are prone to progression and poor prognosis. The best cutoff value for predicting progression was 193.62 pg/mL (sensitivity, 67.5%; specificity 83.7%), and that for poor prognosis was 193.77 pg/mL (sensitivity, 71.1%; specificity, 72.5%). CONCLUSION: The serum level of IPA was an independent predictor of ACI and had certain clinical value for predicting stroke progression and prognosis in patients with ACI.

Quantitative Anatomic Analysis and Clinical Application of Lumbar Spinous Process Split Laminotomy.

AIM: To investigate the feasibility and safety of lumbar spinous process split laminotomy by quantitative anatomic analysis. MATERIAL AND METHODS: Nine fresh adult human cadaveric specimens (including 45 lumbar segments) were divided into 3 groups randomly. The simulated operations and anatomic measurements were performed to evaluate the visibility angle and surgical corridor at different retraction widths (8 mm, 10 mm, and 12 mm). By measuring the width causing bony fracture in 45 lumbar segments, the safety margin of retraction width was determined. The findings of lumbar spinous process split laminotomy in one typical case were presented. RESULTS: At 8 mm retraction width, there was not enough surgical corridor for the operation procedures. At 10 mm and 12 mm retraction width, all operation procedures could be conducted smoothly. The 12 mm group presented a larger surgical corridor and shorter operative time compared with the 10 mm group. The imaging examination confirmed no bony fracture and articular capsule impairment. The visibility angle and exposure extent increased in proportion to the retraction width. The retraction width that resulted in the bony fracture ranged from 12.34 mm to 16.82 mm, with an average of (14.56 ± 1.73) mm. The positions of fracture were in the pedicle of the vertebral arch (68.9%), the lamina (26.7%), and the vertebral body (4.4%). CONCLUSION: The retraction width of 10 mm-12 mm is safe and effective. The micromanipulations such as tumor resection, nervous exploration, dural suture, etc. can be conducted smoothly via the surgical corridor. In addition, the retraction width of 12.34~16.82 mm could serve as a safety margin for surgical planning. Our findings may provide a quantitative reference for clinical application of lumbar spinous process split laminotomy.

Machine Learning-Based Clinical Prediction Models for Acute Ischemic Stroke Based on Serum Xanthine Oxidase Levels.

OBJECTIVE: Early prediction of the onset, progression and prognosis of acute ischemic stroke (AIS) is helpful for treatment decision-making and proactive management. Although several biomarkers have been found to predict the progression and prognosis of AIS, these biomarkers have not been widely used in routine clinical practice. Xanthine oxidase (XO) is a form of xanthine oxidoreductase (XOR), which is widespread in various organs of the human body and plays an important role in redox reactions and ischemia‒reperfusion injury. Our previous studies have shown that serum XO levels on admission have certain clinical predictive value for AIS. The purpose of this study was to utilize serum XO levels and clinical data to establish machine learning models for predicting the onset, progression, and prognosis of AIS. METHODS: We enrolled 328 consecutive patients with AIS and 107 healthy controls from October 2020 to September 2021. Serum XO levels and stroke-related clinical data were collected. We established 5 machine learning models-the logistic regression (LR), support vector machine (SVM), decision tree, random forest, and K-nearest neighbor (KNN) models-to predict the onset, progression, and prognosis of AIS. The area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, negative predictive value, and positive predictive value were used to evaluate the predictive performance of each model. RESULTS: Among the 5 machine learning models predicting AIS onset, the AUROC values of 4 prediction models were over 0.7, while that of the KNN model was lower (AUROC = 0.6708, 95% CI 0.576-0.765). The LR model showed the best AUROC value (AUROC = 0.9586, 95% CI 0.927-0.991). Although the 5 machine learning models showed relatively poor predictive value for the progression of AIS (all AUROCs <0.7), the LR model still showed the highest AUROC value (AUROC = 0.6543, 95% CI 0.453-0.856). We compared the value of 5 machine learning models in predicting the prognosis of AIS, and the LR model showed the best predictive value (AUROC = 0.8124, 95% CI 0.715-0.910). CONCLUSIONS: The tested machine learning models based on serum levels of XO could predict the onset and prognosis of AIS. Among the 5 machine learning models, we found that the LR model showed the best predictive performance. Machine learning algorithms improve accuracy in the early diagnosis of AIS and can be used to make treatment decisions.

Perceived social support mediates the effect of COVID-19 pandemic on job adaptation disorders of workers: An exploratory cross-sectional study.

COVID-19 lockdown can lead to job adaptation disorders, which are heterogeneous among individuals. The purpose of this study was to explore the association between perceived social support and job adaptation disorders among workers in China during the COVID-19 pandemic. The questionnaires of Psychological Questionnaire for Public Health Emergencies, Multidimensional Scale of Perceived Social Support, Work Attitude Scale were used for this cross-section study via an online survey. The study included 626 employees. Hierarchical regression analysis and Bootstrap method were used to investigate the mediation effect of perceived social support between the emergency and job adaptation disorders. The percentages of the 5 dimensions of depression, neurasthenia, fear, compulsion-anxiety, and hypochondria in workers were 59.7%, 56.1%, 92.3%, 42.0%, and 18.7%, respectively. Social support mediated the relationship between depression, neurasthenia, obsessive-compulsive anxiety and job adaptation disorder, accounting for 18.1%, 16.1%, and 17.5% of the total effect (ab/c), respectively. Perceived social support could alleviate COVID-19 pandemic-related depression, neurasthenia, compulsion-anxiety, and job adaptation disorder in Chinese workers. Improving their perception of social support, workers may better adapt themselves to work in the challenging of the public health emergency during COVID-19 pandemic.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

Profiles of phenolics and their synthetic pathways in Asparagus officinalis L.

The synthetic pathways of some phenolics compounds in asparagus have been reported, however, the diversified phenolics compounds including their modification and transcription regulation remains unknown. Thus, multi-omics strategies were applied to detect the phenolics profiles, contents, and screen the key genes for phenolics biosynthesis and regulation in asparagus. A total of 437 compounds, among which 204 phenolics including 105 flavonoids and 82 phenolic acids were detected with fluctuated concentrations in roots (Rs), spears (Ss) and flowering twigs (Fs) of the both green and purple cultivars. Based on the detected phenolics profiles and contents correlated to the gene expressions of screened synthetic enzymes and regulatory TFs, a full phenolics synthetic pathway of asparagus was proposed for the first time, essential for future breeding of asparagus and scaled healthy phenolics production using synthetic biological strategies.

Risk factors and predicting nomogram for the clinical deterioration of non-severe community-acquired pneumonia.

BACKGROUND: Currently, there remains insufficient focus on non-severe community-acquired pneumonia (CAP) patients who are at risk of clinical deterioration, and there is also a dearth of research on the related risk factors. Early recognition of hospitalized patients at risk of clinical deterioration will be beneficial for their clinical management. METHOD: A retrospective study was conducted in The First Affiliated Hospital of Wenzhou Medical University, China, spanning from January 1, 2018 to April 30, 2022, and involving a total of 1,632 non-severe CAP patients. Based on whether their condition worsened within 72 h of admission, patients were divided into a clinical deterioration group and a non-clinical deterioration group. Additionally, all patients were randomly assigned to a training set containing 75% of patients and a validation set containing 25% of patients. In the training set, risk factors for clinical deterioration in patients with non-severe CAP were identified by using LASSO regression analysis and multivariate logistic regression analysis. A nomogram was developed based on identified risk factors. The effectiveness of the nomogram in both the training and validation sets was assessed using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Age, body mass index (BMI), body temperature, cardiovascular comorbidity, respiratory rate, LDH level, lymphocyte count and D-dimer level were identified as risk factors associated with the clinical deterioration of non-severe CAP within 72 h of admission. The area under curve (AUC) value of the nomogram was 0.78 (95% CI: 0.74-0.82) in the training set and 0.75 (95% CI: 0.67-0.83) in the validation set. Furthermore, the calibration curves for both the training and validation sets indicated that the predicted probability of clinical deterioration aligned with the actual probability. Additionally, DCA revealed clinical utility for the nomogram at a specific threshold probability. CONCLUSION: The study successfully identified the risk factors linked to the clinical deterioration of non-severe CAP and constructed a nomogram for predicting the probability of deterioration. The nomogram demonstrated favorable predictive performance and has the potential to aid in the early identification and management of non-severe CAP patients at elevated risk of deterioration.

Development and application of a nomogram model for the prediction of carbapenem-resistant Klebsiella pneumoniae infection in neuro-ICU patients.

IMPORTANCE: Patients in neuro-ICU are at a high risk of developing nosocomial CRKP infection owing to complex conditions, critical illness, and frequent invasive procedures. However, studies focused on constructing prediction models for assessing the risk of CRKP infection in neurocritically ill patients are lacking at present. Therefore, this study aims to establish a simple-to-use nomogram for predicting the risk of CRKP infection in patients admitted to the neuro-ICU. Three easily accessed variables were included in the model, including the number of antibiotics used, surgery, and the length of neuro-ICU stay. This nomogram might serve as a useful tool to facilitate early detection and reduction of the CRKP infection risk of neurocritically ill patients.

The intestinal microflora diversity of aboriginal chickens in Jiangxi province, China.

Intestinal microbiota can coevolve with host to form symbiotic relationship and be participated in the regulation of host physiological function. At present, there is no clear explanation on the effect of intestinal microflora in Jiangxi aboriginal chickens. Here, we investigated the association between gut microbiota and host genome of Jiangxi local chickens using 16S rRNA sequencing and genome-wide association studies (GWAS). The results showed that the breeds and genders had important effects on the intestinal microbiota of chickens. A total of 28 SNPs in 14 regions of the chicken genome were related to the relative abundance of microorganisms in 5 genera: Clostridium_sensu_stricto_1, Enterococcus, Gallibacterium, Turicibacter, and Rikenellaceae_RC9_gut_group. A total of 17 candidate genes were identified composition of chicken microbiome and show an association between the host genome and the chicken intestinal microbiota, which also unveiled the diversity of intestinal microbes in Jiangxi chickens. Given the correlation between chicken genome and intestinal microbe found in the present study, a new idea for the protection of aboriginal chicken genetic resources in China could be provided.

Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of YK-029A in Treatment-Naive Patients With Advanced NSCLC Harboring EGFR Exon 20 Insertion Mutations: A Phase 1 Trial.

INTRODUCTION: Treatment options for treatment-naive patients with advanced NSCLC harboring EGFR exon 20 insertion (ex20ins) mutations are limited. This study evaluated the safety, tolerability, and pharmacokinetics of YK-029A, a third-generation EGFR tyrosine kinase inhibitor, and the preliminary efficacy of YK-029A in treatment-naive patients with EGFR ex20ins mutation. METHODS: This multicenter, dose-escalation, and dose-expansion phase 1 clinical trial enrolled patients with NSCLC harboring EGFR mutations. During the dose-escalation phase, YK-029A was orally administered using the traditional 3+3 principle at 50, 100, 150, 200, and 250 mg/d. In the dose-expansion phase, treatment-naive patients with EGFR ex20ins mutations were enrolled and administered YK-029A 200 mg/d. The primary end point was safety and tolerability. RESULTS: The safety analysis included 108 patients. No dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. The most common treatment-emergent adverse events were anemia (50.9%), diarrhea (49.1%), and rash (34.3%). There was minimal drug accumulation after multiple doses. A total of 28 treatment-naive patients with EGFR ex20ins mutations were enrolled in the dose-expansion and 26 were included in the efficacy analysis. According to the independent review committee evaluation, the objective response rate was 73.1% (95% confidence interval: 52.21%-88.43%), and the disease control rate was 92.3% (95% confidence interval: 74.87%-99.05%). CONCLUSIONS: YK-029A was found to have manageable safety and be tolerable in patients with NSCLC harboring EGFR mutations and have promising antitumor activity in untreated patients with EGFR ex20ins mutations.

Prediction Models for Dysphagia in Intensive Care Unit after Mechanical Ventilation: A Systematic Review and Meta-analysis.

OBJECTIVE: Dysphagia is a common condition that can independently lead to death in patients in the intensive care unit (ICU), particularly those who require mechanical ventilation. Despite extensive research on the predictors of dysphagia development, consistency across these studies is lacking. Therefore, this study aimed to identify predictors and summarize existing prediction models for dysphagia in ICU patients undergoing invasive mechanical ventilation. METHODS: We searched five databases: PubMed, EMBASE, Web of Science, Cochrane Library, and the China National Knowledge Infrastructure. Studies that developed a post-extubation dysphagia risk prediction model in ICU were included. A meta-analysis of individual predictor variables was performed with mixed-effects models. The risk of bias was assessed using the prediction model risk of bias assessment tool (PROBAST). RESULTS: After screening 1,923 references, we ultimately included nine studies in our analysis. The most commonly identified risk predictors included in the final risk prediction model were the length of indwelling endotracheal tube ≥72 h, Acute Physiology and Chronic Health Evaluation (APACHE) II score ≥15, age ≥65 years, and duration of gastric tube ≥72 h. However, PROBAST analysis revealed a high risk of bias in the performance of these prediction models, mainly because of the lack of external validation, inadequate pre-screening of variables, and improper treatment of continuous and categorical predictors. CONCLUSIONS: These models are particularly susceptible to bias because of numerous limitations in their development and inadequate external validation. Future research should focus on externally validating the existing model in ICU patients with varying characteristics. Moreover, assessing the acceptance and effectiveness of the model in clinical practice is needed. LEVEL OF EVIDENCE: NA Laryngoscope, 134:517-525, 2024.

A cytosine analogue 5-azacitidine improves the accumulation of licochalcone A in licorice Glycyrrhiza inflata.

Licochalcone A (LCA) is a characteristic compound of Glycyrrhiza inflata with anti-inflammatory, antioxidant and antitumor activities. However, G. inflata produces LCA in low quantities that does not meet the market demand. In this study, we found that DNA methylation inhibitor 5-azacitidine (5-azaC) successfully improved the LCA contents in G. inflata seedlings. Transcriptome analysis revealed a series of differentially expressed genes (DEGs), including transcription factors such as MYB, ERF, WRKY, and some structural genes related to flavonoid biosynthesis. However, whole genome bisulfite sequencing (BS-seq) results showed little effect of the 5-azaC treatment on the alteration of DNA methylation on these genes, indicating the possibility that 5-azaC acts as a stimulus, but not an epigenetic modulation factor to improve the LCA content in G. inflata. Additionally, we applied the 5-azaC treatment to field plants and hairy roots and successfully increased the LCA contents in both cases. This research demonstrates the feasibility of 5-azaC treatments in future applications to improve plant production of LCA.

Lipidomics reveals immune-related adverse events in NSCLC patients receiving immune checkpoint inhibitor.

There is a lack of reliable biomarkers to predict and identify the risk of immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients undergoing immune checkpoint inhibitor (ICI) treatment. This study aims to explore potential biomarkers using lipidomics to identify and predict the risk of irAEs in NSCLC patients receiving ICI treatment. This prospective study enrolled 94 NSCLC patients with IIIB/IV stage NSCLC who underwent first-line chemotherapy in combination with ICI treatment. The prediction cohort consisted of plasma samples collected from 60 patients before ICI treatment, and the occurrence of irAE was monitored within 6 months of initiating first-line ICI therapy. The validation cohort comprised 34 patients, with plasma samples obtained from 15 patients who did not develop irAE at 6 months of ICI treatment and plasma samples collected from 19 irAE patients at the onset of irAE. Through non-targeted lipidomics and semi-targeted lipid quantification analysis, we identify 11 differentially metabolized lipids and further screened these lipids with the area under the curve (AUC) > 0.7 to predict the occurrence of irAEs in NSCLC patients following ICI treatment. The results showed that the biomarker panel consisting of 9 lipids (LPC-18:2, PC-40:6, LPC-22:6, LPC-O-18:0, PS-38:0, PC-38:6, PC-37:6, PC-36:5,LPC-17:0) exhibited a good AUC of 0.859 in the prediction and 0.940 in the validation cohort phase of the receiver operating characteristic curve; The study utilizes plasma lipidomics to develop a rapid and effective prediction model for identifying irAEs in advanced NSCLC patients who treatment with first-line chemotherapy combined with immunotherapy.

Decoding plant specialized metabolism: new mechanistic insights.

Secondary metabolite (SM) production provides biotic and abiotic stress resistance and enables plants to adapt to the environment. Biosynthesis of these metabolites involves a complex interplay between transcription factors (TFs) and regulatory elements, with emerging evidence suggesting an integral role for chromatin dynamics. Here we review key TFs and epigenetic regulators that govern SM biosynthesis in different contexts. We summarize relevant emerging technologies and results from the model species arabidopsis (Arabidopsis thaliana) and outline aspects of regulation that may also function in food, feed, fiber, oil, or industrial crop plants. Finally, we highlight how effective translation of fundamental knowledge from model to non-model species can benefit understanding of SM production in a variety of ecological, agricultural, and pharmaceutical contexts.

A Peptoid-like Approach Led to Lactam-Lactam Dimer Formation in 2-Hydroxy-N-alkyl-N-phenyl-nicotinamides and Their Polymorphism and Solvatomorphism.

Four 2-hydroxy-N-alkyl-N-phenyl-nicotinamides (1-4) were synthesized, and their crystal structures were analyzed to investigate the effect of substitution on their crystal packing of N-phenyl-2-hydroxynicotinanilides. In these compounds, substituents were introduced on the amide N, leading to a peptoid-like structure. One solvent-free form and two hydrates were harvested for compound 1, and one anhydrous form and one hydrate were obtained for compound 2. Polymorphism was observed in compounds 3 and 4. The molecules were found to be in the keto form rather than the enol tautomer. Because of steric effects, the molecules took on an E configuration, leading to a hairpin-like geometry. A lactam-lactam dimer synthon was formed in all solvent-free structures, and a tetramer motif was observed for the first time. Dehydration of the two hydrates of 1 and the hydrate of 2 led to their respective solvent-free form. Phase transition between the polymorphs was revealed in compound 3. Theoretical calculations, including conformational energy evaluation, hydrate forming propensity assessment, and lattice energy appraisal, were performed to provide a reasonable explanation for the keto tautomer and the formation of the hydrates of compound 1.

Association between the modified lung immune predictive index and clinical outcomes of advanced non-small cell lung cancer treated with first-line immune checkpoint inhibitors combined with chemotherapy.

Background: As revealed by previous studies, the modified lung immune predictive index (mLIPI) can predict outcomes in patients with lung cancer receiving single-agent immunotherapy. However, the application value of the mLIPI for patients treated with combination immunotherapy requires further investigation. In this study, we aimed to explore the relationship between the mLIPI and the efficacy of treatment together with the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving first-line immune checkpoint inhibitors (ICIs) combined with platinum-based chemotherapy. Methods: In this retrospective study, we enrolled patients with advanced NSCLC treated with ICIs plus chemotherapy from March 2019 to June 2022. The patients were classified into good, intermediate, and poor/very poor groups according to their mLIPI before treatment. We further calculated the disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the three groups. The predictive ability of the mLIPI was evaluated by plotting a time-dependent receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Results: A total of 209 patients were included in this study. There were 75 patients in the good group, 114 patients in the intermediate group, and 20 patients in the poor/very poor group. The median PFS was 11.2 months [95% confidence interval (CI): 8.763-13.704] in the good group; 8.1 months (95% CI: 7.354-8.846) in the intermediate group; and 5.4 months (95% CI: 2.142-8.658) in the poor/very poor group. The median OS was not reached in the good group, 29.5 months (95% CI: 23.555-35.512) in the intermediate group, and 14.5 months (95% CI: 8.567-20.366) in the poor/very poor group (P<0.05). Multivariate analysis showed that the mLIPI was independently associated with PFS and OS (P<0.05); the AUC values of the mLIPI for predicting PFS at 3, 6, and 9 months were 0.673, 0.637, and 0.614, respectively, and for predicting OS at 6, 12, and 24 months were 0.715, 0.655, and 0.625, respectively. Conclusions: The pretreatment mLIPI could be used to predict outcomes in patients with NSCLC receiving first-line ICIs plus chemotherapy.

The mediating effect of psychological flexibility on fatigue and depressive symptoms among nursing staff.

Objectives: To explore the relationship between depressive symptoms, fatigue and psychological flexibility, as well as their interactions on depression in Chinese nurses. Material and Methods: Using convenience sampling, a cross-sectional survey of 796 nurses in municipal hospitals of Zhengzhou, Henan Province, China, was conducted. The questionnaires of Work-related Acceptance and Action Questionnaire, Center for Epidemiological Studies Depression Scale and Fatigue Assessment Instrument were used. Hierarchical regression and bootstrap methods were used to examine the mediating effect of psychological flexibility between fatigue and depression. Results: More than 51.8% of the nurses were at risk of depression and 62.3% were at risk of fatigue. There was a significantly positive and moderate correlation between depression and fatigue severity, situation specificity, and consequences (r = 0.43, r = 0.24 and r = 0.31, respectively, p < 0.01). Depression was negatively correlated with psychological flexibility (r = -0.28, p < 0.01). Psychological flexibility had a negative impact on depression with the explained variance increased by 4.2% (ß = -0.211, p < 0.001). The bootstrap method showed that the mediating effect of psychological flexibility accounting for 8.5% and 12.3% on fatigue and depressive symptoms, respectively. Conclusions: Psychological flexibility plays a partial mediating role between the fatigue severity, consequences of fatigue and depressive symptoms of nurses. Hospital managers should improve medical staff work acceptance to alleviate their depressive symptoms. Int J Occup Med Environ Health. 2023;36(4):563-74.

Prevalence, characteristics, and risk factors of venous thromboembolism in patients with brain tumor undergoing craniotomy: a meta-analysis.

BACKGROUND: Brain tumor patients undergoing craniotomy are significantly associated with the development of venous thromboembolism (VTE), while the contributing factors remains controversial. Our study aimed to investigate the prevalence and risk factors for VTE in postoperational brain tumor patients. METHODS: We searched the PubMed, Embase, Web of Science, Medline, and Cochrane Library databases from their inception to July 2023. Article selection, data extraction, and study quality assessment were performed independently by two reviewers. Publication bias was assessed using Egger's and Begg's tests. Stata 15.0 software was used for data analysis. RESULTS: A total of 25 studies were considered, with a total of 49,620 brain tumor individuals. The pooled prevalence of VTE during hospitalization in postoperational brain tumor patients was 9% [95% CI: (0.08, 0.10)]. Moreover, our results demonstrated that patients with VTE were older than those without VTE [mean difference [MD] = 8.14, 95% CI: (4.97, 11.30)]. The following variables were significantly associated with VTE: prior history of VTE [OR = 7.81, 95% CI: (3.62, 16.88)], congestive heart failure [OR = 2.33, 95% CI: (1.08-5.05)], diabetes [OR = 1.87, 95% CI: (1.12-3.10)], hypertension [OR = 1.27, 95% CI: (1.07-1.50)], steroid use [OR = 1.63, 95% CI: (1.41, 1.88)], high white blood cells counts [MD = 0.32, 95% CI: (0.01, 0.63)], and high fibrinogen levels [MD = 0.19, 95% CI: (0.08, 0.30)]. CONCLUSION: This meta-analysis identified risk factors for postoperational VTE in patients with brain tumor, which can serve as a theoretical foundation for medical staff to manage and treat VTE. TRIAL REGISTRATION: CRD42023357459.