Reversible pH-Gated MXene Membranes with Ultrahigh Mono-/Divalent-Ion Selectivity.

Artificial ion channel membranes hold high promise in water treatment, nanofluidics, and energy conversion, but it remains a great challenge to construct such smart membranes with both reversible ion-gating capability and desirable ion selectivity. Herein, we constructed a smart MXene-based membrane via p-phenylenediamine functionalization (MLM-PPD) with highly stable and aligned two-dimensional subnanochannels, which exhibits reversible ion-gating capability and ultrahigh metal ion selectivity similar to biological ion channels. The pH-sensitive groups within the MLM-PPD channel confers excellent reversible Mg2+-gating capability with a pH-switching ratio of up to 100. The mono/divalent metal-ion selectivity up to 1243.8 and 400.9 for K+/Mg2+ and Li+/Mg2+, respectively, outperforms other reported membranes. Theoretical calculations combined with experimental results reveal that the steric hindrance and stronger PPD-ion interactions substantially enhance the energy barrier for divalent metal ions passing through the MLM-PPD, and thus leading to ultrahigh mono/divalent metal-ion selectivity. This work provides a new strategy for developing artificial-ion channel membranes with both reversible ion-gating functionality and high-ion selectivity for various applications.

Construction of a novel Eu-MOF material based on different detection mechanisms and its application in sensing pollutants aniline, F- and Hg2.

Aniline is an organic pollutant with carcinogenicity and teratogenicity, while F- and Hg2+ are toxic ions that are easily soluble in water. When they are released to the environment, they will pose a threat to human health. Designing a material that can simultaneously detect three types of pollutants is of great significance. In this paper, a novel rare earth metal organic framework material (Eu-MOF) with three-dimensional structure based on 1-methylimidazole-4,5-dicarboxylic acid was synthesized for the first time through solvent thermal method. It has excellent luminescent performance and can be used as a multifunctional fluorescent probe to detect aniline, F-, and Hg2+ based on photoinduced electron transfer, energy competitive absorption, and ion exchange mechanisms, with detection limits of 1.79 × 10-8, 8.13 × 10-8, and 8.83 × 10-7 M, respectively. It is worth noting that Eu-MOF can detect F- and Hg2+ in real water samples, such as lake water and green tea water, with favorable recovery rates.

Personalized functional network mapping for autism spectrum disorder and attention-deficit/hyperactivity disorder.

Autism spectrum disorder (ASD) and Attention-deficit/hyperactivity disorder (ADHD) are two typical neurodevelopmental disorders that have a long-term impact on physical and mental health. ASD is usually comorbid with ADHD and thus shares highly overlapping clinical symptoms. Delineating the shared and distinct neurophysiological profiles is important to uncover the neurobiological mechanisms to guide better therapy. In this study, we aimed to establish the behaviors, functional connectome, and network properties differences between ASD, ADHD-Combined, and ADHD-Inattentive using resting-state functional magnetic resonance imaging. We used the non-negative matrix fraction method to define personalized large-scale functional networks for each participant. The individual large-scale functional network connectivity (FNC) and graph-theory-based complex network analyses were executed and identified shared and disorder-specific differences in FNCs and network attributes. In addition, edge-wise functional connectivity analysis revealed abnormal edge co-fluctuation amplitude and number of transitions among different groups. Taken together, our study revealed disorder-specific and -shared regional and edge-wise functional connectivity and network differences for ASD and ADHD using an individual-level functional network mapping approach, which provides new evidence for the brain functional abnormalities in ASD and ADHD and facilitates understanding the neurobiological basis for both disorders.

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.

Susceptibility to Hepatotoxic Drug-Induced Liver Injury Increased After Traumatic Brain Injury in Mice.

The early stages of brain injury can induce acute liver injury, which can be recovered in the short term. Continued medication treatment during hospitalization for brain injury alleviates the prognosis and contributes to a high incidence of drug-induced liver injury (DILI). We hypothesize that there is an interaction between changes in the hepatic environment after brain injury and liver injury produced by intensive drug administration, leading to an upregulation of the organism's sensitivity to DILI. In this study, mice models of TBI were established by controlled cortical impact (CCI) and models of DILI were constructed by acetaminophen (APAP). All mice were divided into four groups: Sham, TBI, APAP, and TBI+APAP, and related liver injury indicators in liver and serum were detected by Western blot, Quantitative real-time PCR (qRT-PCR), and immunohistochemical staining. The results suggested that liver injury induced in the early stages of brain injury recovered in 3 days, but this state could still significantly aggravate DILI, represented by higher liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), oxidative stress (increase in malondialdehyde [MDA] concentration and deregulation of glutathione [GSH] and superoxide dismutase [SOD] activities), inflammatory response (activation of the HMGB1/TLR4/NF-κB signaling pathway, and increased messenger RNA [mRNA] and protein levels of pro-inflammatory cytokines including tumor necrosis factor alpha [TNF-α], interleukin [IL]-6, and IL-1ß), and apoptosis (TUNEL assay, upregulation of Bax protein and deregulation of Bcl-2 protein). In summary, our results suggested that TBI is a potential susceptibility factor for DILI and exacerbates DILI.

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.

Individual-level community-based social capital and depressive symptoms among older adults in urban China: the moderating effects of socioeconomic status.

OBJECTIVES: This study aimed to examine the moderating role of socioeconomic status in the association between community-based social capital-based on individual-level cognitive and structural social capital-and depressive symptoms among older adults in urban China. METHODS: Data were collected in 2020 through a community survey of 800 respondents aged 60 years and older living in Shijiazhuang and Tianjin. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Multiple-group analyses were conducted to analyze the data. RESULTS: Measurement models of cognitive social capital and structural social capital were established. Measurement invariance was established across different socioeconomic groups. Additionally, socioeconomic status significantly moderated the association between social capital and depressive symptoms. The association between cognitive social capital and depressive symptoms was statistically significant among respondents with relatively low incomes and high levels of education, whereas the association between structural social capital and depressive symptoms was significant only among those with relatively high incomes. CONCLUSION: Future social capital policies and interventions should adopt different strategies to provide services to older adults from different socioeconomic backgrounds. Furthermore, educational programs should promote the effects of cognitive social capital on depressive symptoms later in life.

Enhanced stability and bioavailability of mulberry anthocyanins through the development of sodium caseinate-konjac glucomannan nanoparticles.

This study was carried out to improve the stability of anthocyanins (ACNs) by developing MA-SC-KGM nanoparticles using a self-assembly method that involved the combination of sodium caseinate (SC) and konjac glucomannan (KGM) with mulberry anthocyanin extract (MA). Atomic force microscopy (AFM) analysis showed SC encapsulated MA successfully. Multispectral techniques demonstrated the presence of hydrogen bonds and hydrophobic interactions in the nanoparticles. MA-SC-KGM ternary mixture improved storage stability, color stability and anthocyanin retention better compared to the MA-SC binary mixture. Notably, MA-SC-KGM nanoparticles significantly inhibited the thermal degradation of ACNs, improved pH stability, and showed stability and a slow-release effect in gastrointestinal digestion experiments. In addition, MA-SC-KGM nanoparticles were effective in scavenging DPPH· and ABTS+ free radicals, with enhanced stability and antioxidant capacity even during the heating process. This study successfully developed a novel MA-SC-KGM protein-polysaccharide composite material that effectively stabilized natural ACNs, expanding the application of ACNs in various industries.

The role of TRIM family in metabolic associated fatty liver disease.

Metabolic associated fatty liver disease (MAFLD) ranks among the most prevalent chronic liver conditions globally. At present, the mechanism of MAFLD has not been fully elucidated. Tripartite motif (TRIM) protein is a kind of protein with E3 ubiquitin ligase activity, which participates in highly diversified cell activities and processes. It not only plays an important role in innate immunity, but also participates in liver steatosis, insulin resistance and other processes. In this review, we focused on the role of TRIM family in metabolic associated fatty liver disease. We also introduced the structure and functions of TRIM proteins. We summarized the TRIM family's regulation involved in the occurrence and development of metabolic associated fatty liver disease, as well as insulin resistance. We deeply discussed the potential of TRIM proteins as targets for the treatment of metabolic associated fatty liver disease.

CD45- erythroid progenitor cells promote lymph node metastasis in gastric cancer by inducing a hybrid epithelial/mesenchymal state in lymphatic endothelial cells.

BACKGROUND AND AIMS: Specific mechanisms of lymph node (LN) metastasis in early-stage gastric cancer (GC) have not been elucidated. The role of anemia, a vital clinical feature of GC, in LN metastasis is also unclear. Since the number of erythroid progenitor cells (EPCs) is increased in chronic anemia, we investigated its association with LN metastasis in GC. METHODS: Flow cytometry and immunofluorescence analyses were performed to sort and study EPCs from the circulation and tumors of patients with stage I-III GC. The effect of these EPCs on the activation of T and B cells and on the functions of lymphatic endothelial cells (LECs) was determined, and their ability to promote LN metastasis was evaluated using a footpad-popliteal LN metastasis model based on two human adenocarcinoma GC cell lines in nude mice. The prognostic value of EPCs was also analyzed. RESULTS: The proportion of CD45- EPCs was higher in the mononuclear cells in the circulation, tumors, and LNs of GC patients with LN metastasis (N+) than in those of GC patients without LN metastasis (N0). In N+ patients, CD45- EPCs were more abundant in metastatic LNs than in non-metastatic LNs. Lymphatic vessel endothelial hyaluronan receptor 1 immunoreactivity in tumors revealed that CD45- EPCs were positively associated with nodal stages and lymph vessel density. Furthermore, CD45- EPCs increased LEC proliferation and migration through their S100A8/A9 heterodimer-induced hybrid epithelial/mesenchymal (E/M) state; however, they did not influence the invasion and tubulogenesis of LECs or T and B cell proliferation. CD45- EPCs promoted LN metastasis in vivo; the S100A8/A9 heterodimer mimicked this phenomenon. Finally, CD45- EPCs predicted the overall and disease-free survival of stage I-III GC patients after radical resection. CONCLUSIONS: The CD45- EPCs accumulated in GC tissues and metastatic LNs and promoted LN metastasis via the S100A8/9-induced hybrid E/M state of LECs, which was the specific mechanism of LN metastasis in the early stages of GC.

Postoperative serum CHI3L1 level is associated with postoperative cognitive dysfunction in elderly patients after hip fracture surgery: A prospective observational study.

Objectives: Postoperative cognitive dysfunction (POCD) is a common postoperative complication in older patients. Chitinase-3-like-1 protein (CHI3L1) is identified as a neuroinflammatory biomarker and impairs cognitive function. This study aimed to evaluate the association between serum levels of CHI3L1 and POCD and explore the levels of interleukin-6 (IL-6), IL-1ß and C-reactive protein (CRP) in the elderly after total hip arthroplasty (THA). Patients and methods: A total of 76 elderly patients undergoing THA were enrolled in the prospective observational study. Serum CHI3L1 levels were measured 1 day before and 1 day after surgery and other perioperative factors were also noted. The correlations between mediators of inflammation in the two groups were compared via Spearman correlation coefficients. The receiver operating characteristic (ROC) curves were implemented to analyze the predictive values of serum CHI3L1 and other inflammatory factors for POCD. And factors associated with POCD were analyzed by univariate and multivariate logistics. Results: POCD was observed in 31.6% of patients 1 week after surgery. Postoperative serum CHI3L1 levels were higher in POCD patients than in non-POCD patients [1348.26(778.46-1889.77) VS 2322.86(1686.88-2517.35) ng/ml, P < 0.001]. Postoperative serum CHI3L1 level was positively correlated with postoperative IL-6 level (r = 0.284, P = 0.013). Compared with IL-6, IL-1ß, and CRP, postoperative CHI3L1 level has the highest predictive value for POCD with the area under the curve (AUC) value of 0.779 according to the ROC curve. By the multivariate logistic regression analysis, elevated postoperative serum CHI3L1 level was found to be an independent risk factor for POCD 1 week after surgery (odds ratio = 1.204, 95% confidence interval = 1.087-1.332, P = 0.001). Conclusion: Postoperative elevated serum CHI3L1 level was significantly associated with the incident of POCD, and positively correlated with postoperative IL-6 level in the elderly after THA. This biomarker may have potential utility for further elucidating the etiology of POCD.

A deep learning-based interpretable decision tool for predicting high risk of chemotherapy-induced nausea and vomiting in cancer patients prescribed highly emetogenic chemotherapy.

OBJECTIVE: This study aims to develop a risk prediction model for chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving highly emetogenic chemotherapy (HEC) and identify the variables that have the most significant impact on prediction. METHODS: Data from Tianjin Medical University General Hospital were collected and subjected to stepwise data preprocessing. Deep learning algorithms, including deep forest, and typical machine learning algorithms such as support vector machine (SVM), categorical boosting (CatBoost), random forest, decision tree, and neural network were used to develop the prediction model. After training the model and conducting hyperparameter optimization (HPO) through cross-validation in the training set, the performance was evaluated using the test set. Shapley additive explanations (SHAP), partial dependence plot (PDP), and Local Interpretable Model-Agnostic Explanations (LIME) techniques were employed to explain the optimal model. Model performance was assessed using AUC, F1 score, accuracy, specificity, sensitivity, and Brier score. RESULTS: The deep forest model exhibited good discrimination, outperforming typical machine learning models, with an AUC of 0.850 (95%CI, 0.780-0.919), an F1 score of 0.757, an accuracy of 0.852, a specificity of 0.863, a sensitivity of 0.784, and a Brier score of 0.082. The top five important features in the model were creatinine clearance (Ccr), age, gender, anticipatory nausea and vomiting, and antiemetic regimen. Among these, Ccr had the most significant predictive value. The risk of CINV decreased with increased Ccr and age, while it was higher in the presence of anticipatory nausea and vomiting, female gender, and non-standard antiemetic regimen. CONCLUSION: The deep forest model demonstrated good discrimination in predicting the risk of CINV in cancer patients prescribed HEC. Kidney function, as represented by Ccr, played a crucial role in the model's prediction. The clinical application of this predictive tool can help assess individual risks and improve patient care by proactively optimizing the use of antiemetics in cancer patients receiving HEC.

Cerebellum drives functional dysfunctions in restless leg syndrome.

OBJECTIVE: Restless legs syndrome (RLS) has serious effects on patients' sleep quality, physical and mental health. However, the pathophysiological mechanisms of RLS remain unclear. This study utilized both static and dynamic functional activity and connectivity analyses approaches as well as effective connectivity analysis to reveal the neurophysiological basis of RLS. METHODS: The resting-state functional MRI (rs-fMRI) data from 32 patients with RLS and 33 age-, and gender-matched healthy control (HC) were collected. Dynamic and static amplitude of low frequency fluctuation (ALFF), functional connectivity (FC), and Granger causality analysis (GCA) were employed to reveal the abnormal functional activities and couplings in patients with RLS. RESULTS: RLS patients showed over-activities in left parahippocampus and right cerebellum, hyper-connectivities of right cerebellum with left basal ganglia, left postcentral gyrus and right precentral gyrus, and enhanced effective connectivity from right cerebellum to left postcentral gyrus compared to HC. CONCLUSIONS: Abnormal cerebellum-basal ganglia-sensorimotor cortex circuit may be the underlying neuropathological basis of RLS. Our findings highlight the important role of right cerebellum in the onset of RLS and suggest right cerebellum may be a potential target for precision therapy.

Effect of resveratrol on skeletal slow-twitch muscle fiber expression via AMPK/PGC-1α signaling pathway in bovine myotubes.

The purpose of this study was to evaluate the impact of resveratrol on slow-twitch muscle fiber expression in bovine myotubes. The results revealed that resveratrol enhanced slow myosin heavy chain (MyHC) and suppressed fast MyHC protein expression, accompanied by increased MyHC I/IIa and decreased MyHC IIx/IIb mRNA levels in bovine myotubes (P < 0.05). Resveratrol also enhanced the activities of succinic dehydrogenase (SDH), malate dehydrogenase (MDH) and the mitochondrial DNA (mtDNA) content, but reduced lactate dehydrogenase (LDH) activity (P < 0.05). Meanwhile, the protein and gene expression of AMPK, SIRT1 and PGC-1α were upregulated by resveratrol (P < 0.05). Furthermore, PGC-1α inhibitor SR-18292 could attenuate resveratrol-induced muscle fiber conversion from fast-twitch to slow-twitch. These results suggest that resveratrol might promote muscle fiber type transition from fast-twitch to slow-twitch through the AMPK/PGC-1α signaling pathway and mitochondrial biogenesis in bovine myotubes.

Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis.

Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.

Social media use, uncertainty, and negative affect in times of pandemic crisis.

Objective: A common assertion in the social media literature is that passive media use undermines affective wellbeing, and active media use enhances it. The present study investigated the effects of social media use on negative affective wellbeing during pandemic crises and examined the mechanism underlying these effects through perceived uncertainty. Methods: Three studies were conducted during the Delta variant phase in the post-peak period of the COVID-19 pandemic in China. Participants were recruited from the medium-high-risk infection areas in late August 2022. Study 1 used a cross-sectional survey to explore the relationships between social media use, uncertainty, and negative affect during the pandemic crisis. Study 2 employed a repeated-measures experiment to demonstrate how social media use and (un)certainty impact negative affect. Study 3 utilized a one-week experience sampling design to examine the role of uncertainty in the relationship between social media use and negative affect in real life. Results: Despite some inconsistencies regarding social media use's direct effect on negative affect, across the three studies, perceived uncertainty was critical in linking pandemic-related social media use to individuals' negative affect, particularly for passive use. Conclusions: The relationships between social media use and affective wellbeing are complex and dynamic. While the perception of uncertainty provided an underlying mechanism that links social media use to individuals' affective wellbeing, this mechanism may be further moderated by individual-level factors. More research is needed as we seek to understand how social media use impacts affective wellbeing in uncertain contexts.

Effect of Intraoperative Infusion of Esketamine on Quality of Postoperative Recovery in Patients Undergoing Laparoscopic Bariatric Surgery: A Randomized Controlled Trial.

INTRODUCTION: This study aims to evaluate the efficacy of esketamine on postoperative recovery quality after laparoscopic bariatric surgery. METHODS: Patients (n = 74) scheduled for laparoscopic bariatric surgery were randomly divided into two groups: the esketamine group (group E: 0.5 mg/kg/h infusion, i.e., 0.2 mL/kg/h) or the control group (group C: 0.2 mL/kg/h normal saline infusion). The infusions were stopped 20 min before the end of the procedure. The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1 (POD 1). The secondary outcomes included QoR-40 scores on PODs 2 and 7, Numeric Rating Scale (NRS) on PODs 1, 2, and 7, time to extubation, additional postoperative analgesic use, length of hospital stay, and time to first exhaust. Additonally, the safety indices were also recorded, including hemodynamic profile, perioperative anesthesia index (Ai), utilization of vasoactive drugs or urapidil, and side effects. RESULTS: All in all, 70 of the 74 patients completed the study, 35 in each group. The difference of QoR-40 scores on POD 1 was both statistically and clinically significant [difference 7.21, 95% confidence interval (CI) 5.17, 9.25, p < 0.001]. The difference of QoR-40 on POD 2 was statistically significant but clinically insignificant (difference 4.81, 95% CI 2.69, 6.92, p < 0.001). The difference of NRS scores on POD 1 was statistically significant (difference -1.23, 95% CI -2.36, -0.10, p = 0.033). Compared with group C, group E had a lower utilization rate of phenylephrine and higher Ai values (p < 0.05). There was no statistical difference between the two groups on other measures. CONCLUSION: Continuous ketamine infusion seems to be safe and well tolerated in laparoscopic bariatric surgery. It improved the quality of postoperative recovery and reduced pain on POD 1. In spite of the increased Ai value during the surgery, it also provided better hemodynamics with less usage of phenylephrine.

Perioperative lidocaine and dexmedetomidine intravenous infusion reduce the serum levels of NETs and biomarkers of tumor metastasis in lung cancer patients: A prospective, single-center, double-blinded, randomized clinical trial.

Background: Neutrophil extracellular traps (NETs) can enhance the metastasis of non-small cell lung cancer (NSCLC). As biomarkers of tumor metastasis, metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) together with NETs are essential to endothelial-to-mesenchymal transition (EMT). We hypothesized that intravenous infusion of lidocaine and dexmedetomidine could reduce the production of NETs and biomarkers of tumor metastasis after video-assisted thoracic surgery (VATS) in NSCLC patients. Method: The trial included 132 NSCLC patients undergoing VATS. The patients were equally randomized to a placebo group (Group C), a lidocaine group (Group L, intravenous lidocaine 8 mg/kg/h for 15 minutes before anesthesia, 2 mg/kg/h during surgery, and 1 mg/kg/h until 24 hours after surgery), a dexmedetomidine group (Group D, intravenous dexmedetomidine 2 µg/kg/h for 15 minutes before anesthesia, 0.5 µg/kg/h during surgery, and 0.25 µg/kg/h until 24 hours after surgery), and a dexmedetomidine plus lidocaine group (Group LD, combination use of lidocaine and dexmedetomidine). The primary outcome was the production of myeloperoxidase (MPO) and citrullinated histone-3 (H3Cit), biomarkers of NETs, on postoperative day (POD) 1. MMP-3, MMP-9, and VEGF-α, as biomarkers of tumor metastasis, were also evaluated on POD 1. Results: The baseline patient characteristics and perioperative data did not differ between the study groups. MPO was significantly decreased in Groups L, D, and LD (-197.08 ± 34.01, -137.37 ± 32.41, and -189.45 ± 33.73 U/ml, P<0.001, respectively) compared with Group C (-106.51 ± 25.44 U/ml). H3Cit was also lessened in Groups L, D, and LD (-49.51 ± 9.11, -34.80 ± 10.37, and -51.82 ± 8.98 ng/ml, P<0.001, respectively) compared with Group C (-24.73 ± 7.65 ng/ml). Lidocaine and dexmedetomidine also reduced MMP-3 (-69.08 ± 13.22, -52.84 ± 13.78, -85.34 ± 12.59 vs. -40.55 ± 10.71 ng/ml in Group L, D, LD vs. Group C, P<0.001, respectively), MMP-9 (-8.46 ± 1.68, -6.07 ± 1.82, -9.67 ± 1.43 vs. -4.28 ± 1.29 ng/ml in Group L, D, LD vs. Group C, P<0.001, respectively), and VEGF-α (-95.55 ± 22.53, -71.65 ± 18.77, -104.89 ± 15.49 vs. -51.73 ± 16.27 pg/ml in Group L, D, LD vs. Group C, P<0.001, respectively) on POD 1. Conclusion: In NSCLC patients, continuous perioperative intravenous infusion of lidocaine and dexmedetomidine significantly reduced the production of NETs and tumor metastasis biomarkers on POD 1. Meanwhile, it also decreased inflammation, protected cellular immune function, reduced pain and opioid consumption, and improved the quality of postoperative recovery. Clinical trial registration: chictr.org.cn, identifier: 187049.

Evaluation of Retinal Microvascular Features in Patients with Amblyopia Based on Optical Coherence Tomography Angiography: A Systematic Review and Meta-Analysis.

BACKGROUND: The performance of optical coherence tomography angiography (OCTA) in macular microvasculature of patients with amblyopia has been widely studied, but these studies have yielded different and controversial results. OBJECTIVES: The aim of this study is to investigate retinal microvascular features in patients with amblyopia undergoing OCTA. METHODS: PubMed, Embase, and Web of Science were searched for published articles comparing the retinal microvascular features between individuals with amblyopia and controls until April 2022. The mean difference with a 95% confidence interval was used to assess continuous variables. RESULTS: The analysis included 17 studies. The whole vessel density of the superficial capillary plexus (SCPVD) was lower in amblyopic eyes (AE) than in normal eyes (NE) in 3 × 3 mm2 scans, while the perifoveal vessel density of superficial and deep capillary plexus was lower in 6 × 6 mm2 scans. The whole, parafoveal vessel density of deep capillary plexus (DCPVD) and parafoveal SCPVD were lower in both scans. The comparison between AE and fellow eyes (FE) revealed no statistical difference in all quadrants except the parafoveal and perifoveal SCPVD and the foveal DCPVD. Additionally, SCPVD in all quadrants except the fovea and DCPVD in all quadrants except the parafoveal were higher in FE compared to NE. No significant difference was found in the foveal avascular area between AE and NE, AE and FE, or NE and FE. CONCLUSIONS: The retinal vessel density of superficial and deep capillary plexus in AE and FE was lower than in NE, and differences were more likely discovered using 6 × 6 mm2 scans. Consequently, OCTA might be explored as a diagnostic tool to identify and monitor patients with amblyopia.

PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) is a special histopathological subtype of breast cancer. Clinically, IMPC exhibits a higher incidence of lymphovascular invasion and lymph node metastasis compared with that of invasive ductal carcinoma (IDC), the most common type. However, the metabolic characteristics and related mechanisms underlying malignant IMPC biological behaviors are unknown. We performed large-scale targeted metabolomics analysis on resected tumors obtained from chemotherapy-naïve IMPC (n = 25) and IDC (n = 26) patients to investigate metabolic alterations, and we integrated mass spectrometry analysis, RNA sequencing, and ChIP-sequencing data to elucidate the potential molecular mechanisms. The metabolomics revealed distinct metabolic profiles between IMPC and IDC. For IMPC patients, the metabolomic profile was characterized by significantly high levels of arginine methylation marks, and protein arginine methyltransferase 3 (PRMT3) was identified as a critical regulator that catalyzed the formation of these arginine methylation marks. Notably, overexpression of PRMT3 was an independent risk factor for poor IMPC prognosis. Furthermore, we demonstrated that PRMT3 was a key regulator of breast cancer cell proliferation and metastasis both in vitro and in vivo, and treatment with a preclinical PRMT3 inhibitor decreased the xenograft tumorigenic capacity. Mechanistically, PRMT3 regulated the endoplasmic reticulum (ER) stress signaling pathway by facilitating histone H4 arginine 3 asymmetric dimethylation (H4R3me2a), which may endow breast cancer cells with great proliferative and metastatic capacity. Our findings highlight PRMT3 importance in regulating the malignant biological behavior of IMPC and suggest that small-molecule inhibitors of PRMT3 activity might be promising breast cancer treatments.