Glutamatergic neurons in the paraventricular nucleus of the hypothalamus participate in the regulation of visceral pain induced by pancreatic cancer in mice.

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice. Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer. Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain.

Neuroinflammation in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice.

Background: Given the pivotal role of neuroinflammation in chronic pain and that the paraventricular nucleus of the hypothalamus (PVN) is a crucial brain region involved in visceral pain regulation, we sought to investigate whether the targeted modulation of microglia and astrocytes in the PVN could ameliorate pancreatic cancer-induced visceral pain (PCVP) in mice. Methods: Using a mouse model of PCVP, achieved by tumor cell injection at the head of the pancreas, we measure the number of glial cells, and at the same time we employed minocycline to inhibit microglia and chemogenetic methods to suppress astrocytes in order to investigate the respective roles of microglia and astrocytes within the PVN in PCVP. Results: Mice exhibited visceral pain at 12, 15 and 18 days post-tumor cell injection. We observed a significant increase in the population of both microglia and astrocytes. Inhibition of microglial activity through minocycline microinjection into the PVN resulted in alleviation of visceral pain within 30 and 60 min. Similarly, chemogenetic inhibition of astrocyte function at 14 and 21 days post-injection also led to relief from visceral pain. Conclusions: This study found that PVN microglia and astrocytes were involved in regulating PCVP. Our results suggest that targeting glia may be a potential approach for alleviating visceral pain in patients with pancreatic cancer.

Inhibition of GABAergic neurons in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice.

Background: For patients with pancreatic cancer, visceral pain is a debilitating symptom that significantly compromises their quality of life. Unfortunately, the lack of effective treatment options can be attributed to our limited understanding of the neural circuitry underlying this phenomenon. The primary objective of this study is to elucidate the fundamental mechanisms governing visceral pain induced by pancreatic cancer in murine models. Methods: A mouse model of pancreatic cancer visceral pain was established in C57BL/6N mice through the intrapancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were employed to evaluate visceral pain, whereas the in vitro electrophysiological patch-clamp technique was utilized to record the electrophysiological activity of GABAergic neurons. Specific neuron ablation and chemogenetics methods were employed to investigate the involvement of GABAergic neurons in pancreatic cancer-induced visceral pain. Results: In vitro electrophysiological results showed that the firing frequency of GABAergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was decreased. Specific destruction of GABAergic neurons in the PVN exacerbated visceral pain induced by pancreatic cancer. Chemogenetics activation of GABAergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: GABAergic neurons located in PVN play a crucial role in precipitating visceral pain induced by pancreatic cancer in mice, thereby offering novel insights for identifying effective targets to treat pancreatic cancer-related visceral pain.

Global trends of waste-to-energy (WtE) technologies in carbon neutral perspective: Bibliometric analysis.

Waste-to-energy (WtE) technology is at the forefront of low-carbon municipal solid waste (MSW) treatment. MSW has been favoured by researchers in recent years due to its high potential to dispose of resources with WtE technology, which contributes to the carbon neutrality goal. However, there is a lack of research that integrates MSW WtE treatment from a global perspective and explores its future direction. Bibliometric methods are widely used because of their advantages in qualitative and quantitative literature information analysis. A comprehensive search was conducted in the Web of Science (WOS) Core Collection database, covering the period from 1990-2022, resulting in the collection of 702 articles. Subsequently, bibliometric software such as CiteSpace, VOSviewer, and Bibliometrix, were jointly employed for co-occurrence, co-citation, and cluster analyses, providing an in-depth qualitative and quantitative analysis of the research hotspots and development trends of WtE technology for MSW treatment. The research findings indicate a rapid growth in studies on carbon emission reduction through WtE technology for MSW treatment since 2015, with these related articles accounting for 50% of articles. Globally, China, the United States, Italy, and other countries were active research regions, with Chinese research institutions making the largest contributions. However, contributions from developing countries are limited. Furthermore, this study systematically elaborates on the research hotspots in this field. Finally, this study identified some frontier research hotspots and directions. Research on WtE technology primarily focuses on technological methods and policy management, particularly from the carbon neutrality perspective, emphasis WtE technology sustainability in reducing carbon emissions and achieving carbon neutrality goals. Promoting the use of assisted decision-making models in the MSW management process, and focusing on the conversion of food waste into valuable energy. It is hoped that these research directions will provide new ideas for the balanced and rapid development of WtE technology.

MPP2 interacts with SK2 to rescue the excitability of glutamatergic neurons in the BLA and facilitate the extinction of conditioned fear in mice.

AIMS: The basolateral amygdala (BLA) plays an integral role in anxiety disorders (such as post traumatic stress disorder) stem from dysregulated fear memory. The excitability of glutamatergic neurons in the BLA correlates with fear memory, and the afterhyperpolarization current (IAHP ) mediated by small-conductance calcium-activated potassium channel subtype 2 (SK2) dominates the excitability of glutamatergicneurons. This study aimed to explore the effect of MPP2 interacts with SK2 in the excitability of glutamatergic neurons in the BLA and the extinction of conditioned fear in mice. METHODS: Fear memory was analyzed via freezing percentage. Western blotting and fluorescence quantitative PCR were used to determine the expression of protein and mRNA respectively. Electrophysiology was employed to measure the excitability of glutamatergic neurons and IAHP . RESULTS: Fear conditioning decreased the levels of synaptic SK2 channels in the BLA, which were restored following fear extinction. Notably, reduced expression of synaptic SK2 channels in the BLA during fear conditioning was caused by the increased activity of protein kinase A (PKA), while increased levels of synaptic SK2 channels in the BLA during fear extinction were mediated by interactions with membrane-palmitoylated protein 2 (MPP2). CONCLUSIONS: Our results revealed that MPP2 interacts with the SK2 channels and rescues the excitability of glutamatergic neurons by increasing the expression of synaptic SK2 channels in the BLA to promote the normalization of anxiety disorders and provide a new direction for the treatment.

Iron minerals: A frontline barrier against combined toxicity of microplastics and arsenic.

The coexistence of microplastics (MPs) and arsenic (As) in terrestrial ecosystems presents challenges to controlling soil pollution and performing environmental risk assessments. In this study, the interactions among As, polystyrene MPs, and goethite in porous media were investigated and the individual and combined toxicities of MPs and As on wheat germination were evaluated. An additional experiment was conducted to assess the mitigating effect of goethite on the toxicity of the two contaminants. The results showed that the presence of MPs reduced As accumulation in wheat and decreased the acute lethal toxicity of As pollutants (the half-lethal concentration of As during wheat germination increased by 68.21%). However, MPs exhibited inhibitory effects on wheat germination and served as carriers to promote the migration of As within the plant body. The addition of goethite mitigated both individual and combined toxicities and further increased the half-lethal concentration for the combined pollution of As and MPs by 39.48%. This was primarily attributed to the adsorption and immobilization of arsenate and MPs on the medium and root surfaces. In our study, goethite reduced soluble As by 48.29% under the combined pollution scenarios and formed iron plaques on wheat roots, effectively obstructing pollutant entry. Thus, iron minerals serve as pioneering barriers to combined toxicity. Our findings contribute to the understanding of the combined toxicity of MPs and As in crops and offer potential strategies for managing combined pollution.

Development and validation of a regression model with nomogram for difficult video laryngoscopy in Chinese population: a prospective, single-center, and nested case-control study.

Background: Airway management failure is associated with increased perioperative morbidity and mortality. Airway-related complications can be significantly reduced if difficult laryngoscopy is predicted with high accuracy. Currently, there are no large-sample studies on difficult airway assessments in Chinese populations. An airway assessment model based on the Chinese population is urgently needed to guide airway rescue strategy. Methods: This prospective nested case-control study took place in a tertiary hospital in Shanghai, China. Information on 10,549 patients was collected, and 8,375 patients were enrolled, including 7,676 patients who underwent successful laryngoscopy and 699 patients who underwent difficult laryngoscopy. The baseline characteristics, medical history, and bedside examinations were included as predictor variables. Laryngoscopy was defined as 'successful laryngoscopy' based on a Cormack-Lehane Grades of 1-2 and as 'difficult laryngoscopy' based on a Cormack-Lehane Grades of 3-4. A model was developed by incorporating risk factors and was presented in the form of a nomogram by univariate logistic regression, least absolute shrinkage and selection operator, and stepwise logistic regression. The main outcome measures were area under the curve (AUC), sensitivity, and specificity of the predictive model. Result: The AUC value of the prediction model was 0.807 (95% confidence interval [CI]: 0.787-0.828), with a sensitivity of 0.730 (95% CI, 0.690-0.769) and a specificity of 0.730 (95% CI, 0.718-0.742) in the training set. The AUC value of the prediction model was 0.829 (95% CI, 0.800-0.857), with a sensitivity of 0.784 (95% CI, 0.73-0.838) and a specificity of 0.722 (95% CI, 0.704-0.740) in the validation set. Conclusion: Our model had accurate predictive performance, good clinical utility, and good robustness for difficult laryngoscopy in the Chinese population.

Geometric morphometrics and machine learning from three-dimensional facial scans for difficult mask ventilation prediction.

Background: Unanticipated difficult mask ventilation (DMV) is a potentially life-threatening event in anesthesia. Nevertheless, predicting DMV currently remains a challenge. This study aimed to verify whether three dimensional (3D) facial scans could predict DMV in patients scheduled for general anesthesia. Methods: The 3D facial scans were taken on 669 adult patients scheduled for elective surgery under general anesthesia. Clinical variables currently used as predictors of DMV were also collected. The DMV was defined as the inability to provide adequate and stable ventilation. Spatially dense landmarks were digitized on 3D scans to describe sufficient details for facial features and then processed by 3D geometric morphometrics. Ten different machine learning (ML) algorithms, varying from simple to more advanced, were introduced. The performance of ML models for DMV prediction was compared with that of the DIFFMASK score. The area under the receiver operating characteristic curves (AUC) with its 95% confidence interval (95% CI) as well as the specificity and sensitivity were used to evaluate the predictive value of the model. Results: The incidence of DMV was 35/669 (5.23%). The logistic regression (LR) model performed best among the 10 ML models. The AUC of the LR model was 0.825 (95% CI, 0.765-0.885). The sensitivity and specificity of the model were 0.829 (95% CI, 0.629-0.914) and 0.733 (95% CI, 0.532-0.819), respectively. The LR model demonstrated better predictive performance than the DIFFMASK score, which obtained an AUC of 0.785 (95% CI, 0.710-0.860) and a sensitivity of 0.686 (95% CI, 0.578-0.847). Notably, we identified a significant morphological difference in the mandibular region between the DMV group and the easy mask ventilation group. Conclusion: Our study indicated a distinct morphological difference in the mandibular region between the DMV group and the easy mask ventilation group. 3D geometric morphometrics with ML could be a rapid, efficient, and non-invasive tool for DMV prediction to improve anesthesia safety.

Association between the triglyceride glucose (TyG) index and the risk of acute kidney injury in critically ill patients with heart failure: analysis of the MIMIC-IV database.

BACKGROUND: Insulin resistance (IR) can be effectively assessed using the dependable surrogate biomarker triglyceride-glucose (TyG) index. In various critical care contexts, like contrast-induced acute kidney injury (AKI), an elevated TyG index has demonstrated a robust correlation with the incidence of AKI. Nonetheless, the potential of the TyG index to predict AKI in critically ill patients with heart failure (HF) remains uncertain. METHODS: A cohort of participants was non-consecutively selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into quartiles based on their TyG index values. The incidence of AKI was the primary outcome. The secondary endpoint was in-hospital mortality within both the whole study population and the subset of AKI patients. The use of the renal replacement therapy (RRT) which represented the progression of AKI severity was also included as a secondary endpoint representing renal outcome. A restricted cubic splines model and Cox proportional hazards models were utilized to evaluate the association of TyG index with the risk of AKI in patients with HF in a critical condition. Kaplan-Meier survival analysis was employed to estimate primary and secondary endpoint disparities across groups differentiated by their TyG index. RESULTS: This study included a total of 1,393 patients, with 59% being male. The incidence of AKI was 82.8%. Cox proportional hazards analyses revealed a significant association between TyG index and the incidence of AKI in critically ill patients with HF. The restricted cubic splines model illustrated the linear relationship between higher TyG index and increased risk of AKI in this specific patient population. Furthermore, the Kaplan-Meier survival analyses unveiled statistically significant differences in the use of RRT across the subset of AKI patients based on the quartiles of the TyG index. CONCLUSIONS: The results highlight the TyG index as a robust and independent predictor of the incidence of AKI and poor renal outcome in patients with HF in a critical condition. However, further confirmation of causality necessitates larger prospective studies.

Development and validation of a nomogram for difficult laryngoscopy at visual laryngoscopy: a prospective nested case-control study.

Background: Unsuccessful airway management is associated with increased perioperative morbidity and mortality. Difficult laryngoscopy is a leading cause of unanticipated difficult airways and presents a challenge for anesthesiologists. Airway ultrasound assessment can be used as a priority diagnostic strategy for difficult laryngoscopy because of its diagnostic performance in difficult airways. This study was designed to develop a comprehensive model based on multivariate statistical analysis (including bedside examination tests and ultrasonography) for difficult laryngoscopy. Methods: This study was conducted from December 27, 2021, to September 16, 2022. All patients underwent an airway ultrasonographic measurement with a standard operating procedure. The baseline characteristics and bedside examination tests were also recorded. Laryngoscopy with a Cormack-Lehane (CL) grade of 1-2 was defined as "easy laryngoscopy", whereas "difficult laryngoscopy" was based on a CL grade of 3-4. The prediction model was built by using baseline characteristics, bedside examination tests, and ultrasonographic measurements as independent variables and easy/difficult laryngoscopy as the dependent variable. Results: A total of 516 patients were eligible, and 456 patients were finally enrolled in the study. A 4-variable analysis, including inter-incisor gap (IIG), thyromental distance (TMD), the distance from the skin to the tongue root, and airway-related diseases, was performed to construct the optimum prediction model. The area under curve (AUC) value of the prediction model was 0.933 [95% confidence interval (CI): 0.770 to 0.935] in the training set and 0.956 (95% CI: 0.915 to 0.997) in the validation set. Conclusions: The comprehensive model and nomogram, especially the integration of tongue root thickness, can predict the risk of difficult laryngoscopy more accurately and reliably than any other screening method alone, allowing for reasonable individualized regimen decision-making.

Arbuscular mycorrhizal fungi community analysis revealed the significant impact of arsenic in antimony- and arsenic-contaminated soil in three Guizhou regions.

Introduction: The lack of systematic investigations of arbuscular mycorrhizal fungi (AMF) community composition is an obstacle to AMF biotechnological applications in antimony (Sb)- and arsenic (As)-polluted soil. Methods: Morphological and molecular identification were applied to study the AMF community composition in Sb- and As-contaminated areas, and the main influencing factors of AMF community composition in Sb- and As-contaminated areas were explored. Results: (1) A total of 513,546 sequences were obtained, and the majority belonged to Glomeraceae [88.27%, 193 operational taxonomic units (OTUs)], followed by Diversisporaceae, Paraglomeraceae, Acaulosporaceae, Gigasporaceae, and Archaeosporaceae; (2) the affinity between AMF and plants was mainly related to plant species (F = 3.488, p = 0.022 < 0.050), which was not significantly correlated with the total Sb (TSb) and total As (TAs) in soil; (3) the AMF spore density was mainly related to the available nitrogen, available potassium, and total organic carbon; (4) The effect of soil nutrients on AMF community composition (total explanation: 15.36%) was greater than that of soil Sb and As content (total explanation: 5.80%); (5) the effect of TAs on AMF community composition (λ = -0.96) was more drastic than that of TSb (λ = -0.21), and the effect of As on AMF community composition was exacerbated by the interaction between As and phosphorus in the soil; and (6) Diversisporaceae was positively correlated with the TSb and TAs. Discussion: The potential impact of As on the effective application of mycorrhizal technology should be further considered when applied to the ecological restoration of Sb- and As-contaminated areas.

CuCoO2 Nanoparticles as a Nanoprotease for Selective Proteolysis with High Efficiency at Room Temperature.

Many nanoproteases contain tetravalent metal ions and catalyze peptide-bond hydrolysis only at high temperature (60 °C). Here, we report a new and effective strategy to explore nanoproteases from nanoparticles containing low valent metal ions. We found that flower-like CuCoO2 nanoparticles (CuCoO2 NPs) containing low valent Cu+ possessed excellent catalytic activity towards selective cleavage of peptide bonds with hydrophobic residues in bovine serum albumin (BSA) at room temperature. CuCoO2 NPs exhibited excellent stability and had great reusability. CuCoO2 NPs also hydrolyzed heat-denatured and surfactant-denatured BSA. Mechanism analysis revealed that the high Lewis acidity of Co3+ and the low valence of Cu+ were both essential for the high protease activity of CuCoO2 NPs. The flower-like structure of CuCoO2 NPs and the strong nucleophilicity of Cu+ -bound hydroxyl endow them with excellent catalytic performance. The findings open a new way for the design and discovery of high-efficiency nanoproteases.

Gentiopicroside enhances the protective effect of trimetazidine against myocardial ischemia-reperfusion injury via the AMPK/NLRP3 inflammasome signaling.

Myocardial ischemia-reperfusion injury (MI/R) leads to the inevitable clinical consequences of myocardial infarction and subsequent heart failure. Trimetazidine (TMZ), an anti-ischemic agent, exerts protective potential in MI/R but had limited efficacy for some patients. Here we sought to investigate the single and combined application of gentiopicroside (GPS) and TMZ in MI/R. Notably, GPS had little cytotoxicity to cardiomyocytes. GPS attenuated hypoxia/reoxygenation (H/R)-induced cell death, reactive oxygen species production, lactate dehydrogenase and malondialdehyde releases, and antioxidant stress enzyme superoxide dismutase activity, indicating the protective efficacy of GPS against H/R-induced oxidative injury. Importantly, GPS enhanced the protective efficacy of TMZ against H/R-mediated cardiomyocyte injury. Additionally, GPS mitigated the transcription and releases of pro-inflammatory cytokine interleukin-6 and tumor necrosis factor-α in H/R-treated cardiomyocytes, which were enhanced after co-treatment with TMZ. Mechanistically, GPS activated the AMP-activated protein kinase (AMPK) signaling to inhibit H/R-induced NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome, which was further enhanced after costimulation with TMZ. Importantly, blocking the AMPK signaling reversed the protective roles of GPS and its combination with TMZ in H/R-induced oxidative insult and inflammation. In vivo, both GPS and TMZ alleviated the abnormal cardiac structure, cardiomyocyte apoptosis, and cardiac dysfunction in MI/R rats, which were further enhanced after administration with GPS and TMZ together. Furthermore, GPS intensified TMZ-mediated inhibition of oxidative injury, inflammation, and the AMPK/NLRP3 signaling in MI/R rats. Collectively, GPS enhances the protective efficacy of TMZ against MI/R injury through AMPK activation-mediated inhibition of NLRP3 inflammasome signaling, implying a promising therapeutic agent for the treatment of MI/R.

Diagnostic value of peripheral blood miR-296 combined with vascular endothelial growth factor B on the degree of coronary artery stenosis in patients with coronary heart disease.

OBJECTIVE: Coronary heart disease (CHD) is a disorder resulting from organic and functional coronary artery stenosis (CAS), thus causing reduced oxygenated blood in the heart. miRNAs are useful biomarkers in the diagnosis of atherosclerosis, CHD, and acute coronary syndrome. Vascular endothelial growth factor (VEGF) is closely related to CHD. This study explored the correlation of miR-296 and VEGF-B expression levels in peripheral blood with CAS degree in CHD patients. METHODS: Totally 220 CHD patients were enrolled and classified into mild-(71 cases)/moderate-(81 cases)/severe-CAS (68 cases) groups, with another 80 healthy cases as controls. The serum miR-296 and VEGF-B expression levels were detected using reverse transcription quantitative polymerase chain reaction. The correlation between miR-296 and CAS-related indexes was assessed via Pearson analysis. The binding relationship of miR-296 and VEGF-B was first predicted and their correlation was further analyzed via the Pearson method. The clinical diagnostic efficacy of miR-296 or VEGF-B on CAS degree was evaluated by the receiver operating characteristic curve. RESULTS: Serum miR-296 was downregulated in CHD patients and was the lowest in patients with severe-CAS. miR-296 was negatively-correlated with high-sensitivity C-reactive protein, brain natriuretic peptide, and cardiac troponin I. miR-296 targeted VEGF-B. VEGF-B was upregulated in CHD patients and inversely-related to miR-296. Low expression of miR-296 and high expression of VEGF-B both had high clinical diagnostic values on CAS degree in CHD patients. miR-296 combined with VEGF-B increased the diagnostic value on CAS. CONCLUSION: Low expression of miR-296 combined with high expression of its target VEGF-B predicts CAS degree in CHD patients.

MicroRNA-499-5p promotes vascular smooth muscle cell proliferation and migration via inhibiting SOX6.

Atherosclerosis (AS) is the primary etiology of cardiovascular disease, which is considered the leading cause of death all over the world. MicroRNA miR-499-5p was involved in the functional regulation of myocardial and skeletal muscle, whereas its role in atherosclerosis, especially in vascular smooth muscle cells (VSMCs), remains unclear. Our study aims to investigate the effects of miR-499-5p in the proliferation and migration of VSMCs and potential mechanisms. We used mouse aortic vascular smooth muscle cells (MOVAS) and ApoE-/- mice to establish the models of AS in vitro and in vivo, respectively. RT-PCR was performed to detect the expression level of miR-499-5p. Subsequently, Cell Counting Kit-8 (CCK-8) assays, Transwell assays, and wound-healing assays were used to evaluate cell proliferation and migration. Dual-luciferase reporter assay was performed to validate the interaction between miR-499-5p and SOX6. miR-499-5p significantly increased in aorta tissues of mice in AS tissues and vascular smooth muscle cells treated with ox-LDL. miR-499-5p overexpression could promote the proliferation and migration of MOVAS. Bioinformatics analysis predicted and further experiments verified that miR-499-5p could directly bind to the 3'-untranslated region (UTR) region of SOX6. Further, miR-499-5p induced an increased expression of smooth muscle proliferation and migration-related genes, PCNA, cyclin D1, and matrix metalloproteinase (MMP2), as well as the decreased expression of proliferation inhibiting factor p21, which was significantly reversed by SOX6 overexpression. miR-499-5p boosts the proliferation and migration of smooth muscle cells by binding and inhibiting SOX6 expression. The miR-499-5p/SOX6 axis may present a promising therapeutic implication for the prevention and treatment of cardiovascular diseases.

The development of prediction model for cuffed tracheal tube size from the middle finger in pediatrics: a concise and feasible approach.

Background: Selecting the optimal tracheal tube size is critically important for pediatric patients. Age-based formulas are often used, but still have limitations. The aim of this prospective study was to investigate whether middle finger measurements correlate with cuffed tracheal tube size and to further develop a prediction model based on these measurements. Methods: Patients under 12 years of age scheduled for elective surgery involving tracheal intubation were enrolled in the study. The length was determined from the tip of the distal metacarpal to the palm's root on the palm side, while the circumference was measured at the base of the palm using a soft tape measure. The appropriate cuffed tracheal tube size was determined based on specific criteria. If the tube encountered resistance during insertion or required an airway pressure >25 cmH2O to detect an audible leak, it was replaced with a tube 0.5 mm smaller. Conversely, if an audible leak occurred at an airway pressure <10 cmH2O, or peak pressure >25 cmH2O, or the cuff pressure >25 cmH2O to achieve a seal, the tube was exchanged for one with a 0.5 mm larger. Linear regression analysis was used to examine the association between middle finger circumference and length with the cuffed tracheal tube size. Subsequently, regression equations were constructed based on the results of the linear regression analysis and their predictive performance was compared to the conventional age-based formulas, including the Khine formula and Motoyama formula. The predictive performance was evaluated by mean absolute error (MAE), root mean square error (RMSE), and prediction accuracy. Results: A total of 261 patients were analyzed in our study. The mean age of the patients was 46.19±35.83 months. The linear relationship was observed between the cuffed tracheal tube size and the middle finger circumference and middle finger length with R2 values of 0.77 and 0.73, respectively. In comparison to conventional age-based formulas, both middle finger circumference and middle finger length demonstrated superior predictive performance, characterized by lower MAE and RMSE, as well as higher prediction accuracy. Notably, the regression equation based on the middle finger circumference obtained the higher predictive accuracy of 0.590, with an MAE of 0.259 and an RMSE of 0.333 as opposed to the predictive accuracy of 0.391, MAE of 0.349, and RMSE of 0.473 derived from conventional age-based formulas. Based on the regression coefficients of linear regression, simplified formulas were proposed, with the middle finger circumference-based formula emerging as the most accurate and simple option. Conclusions: The appropriate cuffed tracheal tube size could be predicted by the middle finger circumference. Our proposed formula 'cuffed tracheal tube internal diameter (mm) = middle finger circumference (cm) - 0.2' has the potential to improve the selection of the cuffed tracheal tube size in pediatric patients.

Sex-dependent effects of postweaning exposure to an enriched environment on visceral pain and anxiety- and depression-like behaviors induced by neonatal maternal separation.

Background: Neonatal maternal separation (NMS) can lead to visceral pain and anxiety- and depression-like behaviors. An enriched environment (EE) can alleviate NMS-induced pain and mental disorders, but previous studies have mostly been performed in male animals. Therefore, the aim of this study was to investigate whether the effects of EE were sex dependent at different stages of development. Methods: Female and Male C57BL/6 J mice that had been subjected to NMS alone and those subjected to both NMS and exposed to EE were used in this study. The visceral pain threshold test (PTT), open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST) were conducted to evaluate visceral pain, anxiety-like behavior, and depression-like behavior in mice, respectively. Results: Compared with the male mice in the NMS group without EE exposure, those exposed to EE from postnatal day (P)21 to 41 showed an increase of the visceral pain threshold in the PTT, an increase of the central time and central distance in the OFT, an increase of the sucrose preference rate in the SPT, and a decrease of the time of immobility in the FST. Compared with both female and male mice in the NMS group without EE exposure, those exposed to EE from P21 to P61 had an increase of the visceral pain threshold in the PTT, an increase of the central time and central distance in the OFT, an increase in the sucrose preference rate in the SPT, and a decrease of the time of immobility in the FST. Conclusions: EE is more effective in male NMS mice, while longer EE is required in female NMS mice for positive effects.

The influence of the enriched environment in different periods on neonatal maternal separation-induced visceral pain, anxiousness, and depressive behaviors.

Background: Neonatal maternal separation (NMS) is a major early life stress that can induce visceral pain and mental disorders. We have shown that an enriched environment (EE) can alleviate NMS-induced negative effects, but the time window over which EE works is unclear. Therefore, this study aimed to investigate the time window through which EE alleviates NMS-induced visceral pain, anxiousness, and depressive behaviors. Methods: In this study, we used male C57BL/6J mice. The mice were randomly divided into five groups: control group, NMS group, prepubertal EE group (EE1 group), pubertal EE group (EE2 group), and adult EE group (EE3 group). The visceral pain threshold test (PTT), open field test (OFT), elevated plus maze (EPM), forced swimming test (FST), and sucrose preference test (SPT) were performed in all five groups to assay visceral pain, anxiety-, and depression-like behaviors in mice, respectively. Enzyme-linked immunosorbent assay (ELISA) for corticosterone was performed in all five groups to assess the function of the hypothalamic-pituitary-adrenal (HPA) axis. Results: There was no significant change in weight between groups. It was shown that NMS induced visceral pain, anxiety, and depression, and EE1 and EE2 reversed these negative effects, but EE3 had no significant effect. Likewise, EE1 and EE2 reversed the NMS-induced increase of corticosterone, but EE3 did not. Conclusions: Adverse life experiences in early life can lead to visceral pain, anxiety, and depression in adulthood, which can be effectively prevented by EE interventions in prepuberty and puberty.

Enriched environment alleviates adolescent visceral pain, anxiety- and depression-like behaviors induced by neonatal maternal separation.

Background: Neonatal maternal separation (NMS), a major kind of early life stress, increases the risk of visceral pain, anxiety- and depression-like behaviors in adulthood. An enriched environment (EE) has been shown to successfully rescue the brain from various early life psychological stressors. Therefore, this study aimed to investigate whether NMS induces visceral pain, anxiety- and depression-like behaviors in adolescents and to evaluate the impact of EE in infancy on these symptoms. Methods: Male C57BL/6 J mice that had been subjected to NMS were used in this study. The visceral pain threshold test (PTT), open field test (OFT), and sucrose preference test (SPT) were conducted to evaluate visceral pain, anxiety- and depression-like behaviors in mice, respectively. An enzyme linked immunosorbent assay (ELISA) for tumor necrosis factor-α (TNF-α), interleukin-1ß, (IL-1ß), and interleukin-10 (IL-10) was performed to assess neuroinflammatory responses. Then, the effects of EE (free-turning running wheels, pipes, stairs, and various colored ocean balls, etc.) on NMS-induced behaviors and neuroinflammatory factors were examined. Results: The impacts of NMS included adolescent visceral pain, anxiety- and depression-like behaviors. The medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and paraventricular nucleus (PVN) were biased towards pro-inflammatory features. Further, EE alleviated adolescent visceral pain, anxiety- and depression-like behaviors. The application of EE up-regulated the expression of IL-10, and down-regulated the expression of IL-1ß and TNF-α in mPFC, BLA, and PVN. Conclusions: The effects of NMS include adolescent visceral pain, anxiety- and depression-like behaviors, accompanied by an imbalance of neuroinflammation. Intervention with EE in pediatric mice relieved these symptoms by reducing neuroinflammation in the central nervous system.

Microglia-derived TNF-α inhibiting GABAergic neurons in the anterior lateral bed nucleus of the stria terminalis precipitates visceral hypersensitivity induced by colorectal distension in rats.

Irritable bowel syndrome (IBS) is a common and debilitating gastrointestinal disorder that is exacerbated by stress and characterized by abdominal pain. Although microglia in the CNS have been implicated as an important mediator of the stress response, the role of microglia and microglia-GABAergic neuron interactions in the limbic area, most notably BNST, in the development of colorectal hypersensitivity has not been determined. We established a neonatal colorectal distension-induced chronic visceral hyperalgesia model in rats. The results showed that the frequency of spontaneous discharges of alBNST GABAergic neurons and the expression of GAD65/67 were significantly decreased in rats with chronic visceral pain. Moreover, ablation of BNST GABAergic neurons significantly reduced the visceral pain threshold in normal rats. Meanwhile, the number of M1 proinflammatory microglia and the expression of the M1 proinflammatory microglia-derived cytokines IL-6 and TNF-α were increased in the alBNST of rats with chronic visceral pain. Furthermore, alBNST infusion of the microglial inhibitor minocycline or IL-6 and TNF-α neutralizing antibodies significantly increased the visceral pain threshold. The decreased frequency of spontaneous discharges of alBNST GABAergic neurons in rats with chronic visceral pain was mimicked by a bath perfusion of TNF-α, but not IL-6, and was abolished by a perfusion of the microglial inhibitor minocycline. In addition, the alBNST infusion of the microglial inhibitor minocycline upregulated the expression of GAD65/67. Moreover, ablation of BNST GABAergic neurons significantly decreased the visceral pain threshold in normal rats, which was not reversed by a subsequent infusion of the microglial inhibitor minocycline. Our findings revealed this microglia-GABAergic neuron circuit in the alBNST, and this microglia-driven disinhibitory mechanism is essential for brain and gut dysfunction in stressful condition, providing a novel potential target for treating patients with IBS presenting visceral pain that is worsened during episodes of stress.