The safety of preoperative carbohydrate drinks in extremely elderly patients assessed by gastric ultrasonography: a randomized controlled trial.

BACKGROUND: Modern perioperative guidelines encourage drinking oral carbohydrates 2 h before management. Nevertheless, research on the safety of preoperative carbohydrate drinks, particularly in extremely elderly patients is lacking. We aimed to evaluate the safety of carbohydrate drinks 2 h before surgery in extremely elderly patients (≥ 80 years) using gastric ultrasonography. METHODS: We conducted a randomized prospective comparative study of 70 patients aged over 80 years who were scheduled for total knee arthroplasty, hip fracture or humerus fracture surgery. These patients were randomly assigned to the carbohydrate group (n = 35), which fasted from midnight, except for drinking 355 mL of a carbohydrate-containing fluid 2 h before surgery, or the fasting group (n = 35), which fasted from midnight and drank no fluid before surgery. The primary outcome of the study was the cross-sectional area (CSA) of the gastric antrum in the right lateral decubitus position (RLDP) before surgery. The secondary outcomes included CSA in the supine position, intraoperative blood glucose levels and their variability coefficients, Perlas grade, and the visual analog scale of subjective feelings. RESULTS: The CSA in the RLDP and supine positions revealed no differences between the carbohydrate and fasting groups at 0 h preoperatively (P > 0.05). In the qualitative assessment, preoperative 0-h Perlas grading did not differ significantly between the groups (P > 0.05). From 2 h before surgery to transfer out of the post-anesthesia care unit, the average blood glucose level of patients in the carbohydrate group was significantly higher than that in the fasting group (P < 0.001) but remained within the normal range. Moreover, the blood glucose variability coefficient was significantly lower in the carbohydrate group than in the fasting group (P = 0.009). Oral intake of 355 mL carbohydrates before surgery significantly relieved patients' feelings (P < 0.001). CONCLUSION: Preoperative consumption of carbohydrate drinks 2 h before surgery is safe in "healthy" extremely elderly patients. In addition, preoperative drinking has potential value in maintaining ideal blood glucose levels and stable blood glucose fluctuations perioperatively and improving subjective perceptions of preoperative preparation. This finding warrants further investigation in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registration Number ChiCTR1900024812), first registered on 29/07/2019.

Lack of S1PR2 in Macrophage Ameliorates Sepsis-associated Lung Injury through Inducing IL-33-mediated Type 2 Immunity.

The function of type 2 immunity and mechanisms underlying the initiation of type 2 immunity after sepsis-induced lung injury remain unclear. Sphingosine-1-phosphate receptor 2 (S1PR2) has been demonstrated to modulate type 2 immunity in the context of asthma and pulmonary fibrosis. Thus, this study aims to investigate the role of type 2 immunity and whether and how S1PR2 regulates type 2 immunity in sepsis. Peripheral type 2 immune responses in patients with sepsis and healthy control subjects were assessed. The impact of S1PR2 on type 2 immunity in patients with sepsis and in a murine model of sepsis was further investigated. The type 2 innate immune responses were significantly increased in the circulation of patients 24 hours after sepsis, which was positively related to clinical complications and negatively correlated with S1PR2 mRNA expression. Animal studies showed that genetic deletion or pharmacological inhibition of S1PR2 induced type 2 innate immunity accumulation in the post-septic lungs. Mechanistically, S1PR2 deficiency promoted macrophage-derived interleukin (IL)-33 increase and the associated type 2 response in the lung. Furthermore, S1PR2-regulated IL-33 from macrophages mitigated lung injury after sepsis in mice. In conclusion, a lack of S1PR2 modulates the type 2 immune response by upregulating IL-33 release from macrophages and alleviates sepsis-induced lung injury. Targeting S1PR2 may have potential therapeutic value for sepsis treatment.

Transferrin receptor modulated by microRNA-497-5p suppresses cervical cancer cell malignant phenotypes.

BACKGROUND: Cervical cancer is prevalent throughout the world, and microRNA-497-5p (miR-497-5p) plays an important role in its development. However, the specific mechanism by which miR-497-5p targets the transferrin receptor (TFRC) during cervical cancer development has not been clarified. OBJECTIVES: The aim of the study was to unravel TFRC expression and its role in cervical cancer cells, as well as the impact of the miR-497-5p/TFRC axis on cervical cancer cells. MATERIAL AND METHODS: The target mRNA was determined through differential analysis, followed by the evaluation of its impact on survival and clinical staging. Then, quantitative real-time polymerase chain reaction (qPCR) was conducted to analyze the TFRC mRNA level in cervical cancer cells and normal cervical epithelial cells. Western blot (WB) was utilized to examine the expression levels of TFRC, cleaved caspase-3, cleaved caspase-9, and epithelial-mesenchymal transition (EMT)-related proteins. The miRNAs upstream of the target mRNA were predicted, and Pearson correlation analysis was performed, followed by the validation through the dual-luciferase reporter assay. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays were performed to analyze cancer cell viability, followed by a transwell assay aimed at measuring cell migratory and invasive abilities. Finally, flow cytometry was conducted to examine cell apoptosis and cell cycle. RESULTS: The transferrin receptor was significantly increased in cervical cancer cells and positively associated with clinical T and N stages. Silencing TFRC could constrain cell proliferative, migratory and invasive abilities, arrest the cell cycle and facilitate cell apoptosis in cervical cancer cells. The bioinformatics analysis showed a significantly negative correlation between miR-497-5p and TFRC in cervical cancer. Moreover, upregulated miR-497-5p hampered cervical cancer progression and decreased TFRC expression. The overexpression of TFRC reversed the suppressive impact of miR-497-5p overexpression on cervical cancer progression. CONCLUSIONS: The modulatory role of the miR-497-5p/TFRC axis was confirmed in cervical cancer cells. This axis may present a new avenue for the diagnosis of cervical cancer and provide a novel target for cervical cancer treatment.

Pingchuanning Decotion Alleviates Bronchial Asthma Airway Inflammation Through ROS/HMGB1/Beclin-1 Mediated Cell Autophagy.

Objective: Bronchial asthma is a prevalent respiratory disorder characterized by airway inflammation. This study aimed to investigate the protective effect of Pingchuanning decoction (PCN) on airway inflammation in bronchial asthma, focusing on the role of autophagy and its underlying molecular mechanism. Methods: Using an in vitro lipopolysaccharide (LPS)-induced inflammatory damage model of human airway epithelial cells (16HBE), we assessed the effect of PCN. Various experiments were performed to evaluate the expression of autophagy-related genes, autophagosome and vesicle counts, and reactive oxygen species (ROS) levels. Results: First, PCN reduced LPS-induced cellular inflammation. Second, PCN decreased the number of autophagosomes and autophagic vesicles. And third, PCN significantly reduced reactive oxygen species (ROS) levels. Most importantly, PCN also down-regulated LPS-induced expression of HMGB1, Beclin-1, and autophagy-related gene 5 (ATG5) while enhancing the expression of B-cell lymphoma 2 (Bcl-2), which further reduced the LC3II/I ratio. Conclusion: PCN reduces the 16HBE inflammatory response by inhibiting the overexpression of ROS/HMGB1/Beclin-1 mediated cell autophagy. Therefore, it may serve as a potential drug for treating bronchial asthma.

Fusing Positive and Negative CT Contrast Nanoagent for the Sensitive Detection of Hepatoma.

Positive computed tomography (CT) contrast nanoagent has significant applications in diagnosing tumors. However, the sensitive differentiation between hepatoma and normal liver tissue remains challenging. This challenge arises primarily because both normal liver and hepatoma tissues capture the nanoagent, resulting in similar positive CT contrasts. Here, a strategy for fusing positive and negative CT contrast nanoagent is proposed to detect hepatoma. A nanoagent Hf-MOF@AB@PVP initially generates a positive CT contrast signal of 120.3 HU in the liver. Subsequently, it can specifically respond to the acidic microenvironment of hepatoma to generate H2 , further achieving a negative contrast of -96.0 HU. More importantly, the relative position between the negative and positive signals area is helpful to determine the location of hepatoma and normal liver tissues. The distinct contrast difference of 216.3 HU and relative orientation between normal liver and tumor tissues are meaningful to sensitively distinguish hepatoma from normal liver tissue utilizing CT imaging.

Persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery: A case report.

BACKGROUND: Empty sella is an anatomical and radiological finding of the herniation of the subarachnoid space into the pituitary fossa leading to a flattened pituitary gland. Patients with empty sella may present with various symptoms, including headache due to intracranial hypertension and endocrine symptoms related to the specific pituitary hormones affected. Here, we report a female patient who developed persistent postoperative hypotension caused by subclinical empty sella syndrome after a simple surgery. CASE SUMMARY: A 47-year-old woman underwent vocal cord polypectomy under general anesthesia with endotracheal intubation. She denied any medical history, and her vital signs were normal before the surgery. Anesthesia and surgery were uneventful. However, she developed dizziness, headache and persistent hypotension in the ward. Thus, intravenous dopamine was started to maintain normal blood pressure, which improved her symptoms. However, she remained dependent on dopamine for over 24 h without any obvious anesthesia- and surgery-related complications. An endocrine etiology was then suspected, and further examination showed a high prolactin level, a low normal adrenocorticotropic hormone level and a low cortisol level. Magnetic resonance imaging of the brain revealed an empty sella. Therefore, she was diagnosed with empty sella syndrome and secondary adrenal insufficiency. Her symptoms disappeared one week later after daily glucocorticoid supplement. CONCLUSION: Endocrine etiologies such as pituitary and adrenal-related dysfunction should be considered in patients showing persistent postoperative hypotension when anesthesia- and surgery-related factors are excluded.

Predicting post-resection recurrence by integrating imaging-based surrogates of distinct vascular patterns of hepatocellular carcinoma.

Background & Aims: Distinct vascular patterns, including microvascular invasion (MVI) and vessels encapsulating tumour clusters (VETC), are associated with poor outcomes of hepatocellular carcinoma (HCC). Imaging surrogates of these vascular patterns potentially help to predict post-resection recurrence. Herein, a prognostic model integrating imaging-based surrogates of these distinct vascular patterns was developed to predict postoperative recurrence-free survival (RFS) in patients with HCC. Methods: Clinico-radiological data of 1,285 patients with HCC from China undergoing surgical resection were retrospectively enrolled from seven medical centres between 2014 and 2020. A prognostic model using clinical data and imaging-based surrogates of MVI and VETC patterns was developed (n = 297) and externally validated (n = 373) to predict RFS. The surrogates (i.e. MVI and VETC scores) were individually built from preoperative computed tomography using two independent cohorts (n = 360 and 255). Whether the model's stratification was associated with postoperative recurrence following anatomic resection was also evaluated. Results: The MVI and VETC scores demonstrated effective performance in their respective training and validation cohorts (AUC: 0.851-0.883 for MVI and 0.834-0.844 for VETC). The prognostic model incorporating serum alpha-foetoprotein, tumour multiplicity, MVI score, and VETC score achieved a C-index of 0.748-0.764 for the developing and external validation cohorts and generated three prognostically distinct strata. For patients at model-predicted medium risk, anatomic resection was associated with improved RFS (p <0.05). By contrast, anatomic resection had no impact on RFS in patients at model-predicted low or high risk (both p >0.05). Conclusions: The proposed model integrating imaging-based surrogates of distinct vascular patterns enabled accurate prediction for RFS. It can potentially be used to identify HCC surgical candidates who may benefit from anatomic resection. Impact and implications: MVI and VETC are distinct vascular patterns of HCC associated with aggressive biological behaviour and poor outcomes. Our multicentre study provided a model incorporating imaging-based surrogates of these patterns for preoperatively predicting RFS. The proposed model, which uses imaging detection to estimate the risk of MVI and VETC, offers an opportunity to help shed light on the association between tumour aggressiveness and prognosis and to support the selection of the appropriate type of surgical resection.

Comparison of 95% effective dose of remimazolam besylate and propofol for gastroscopy sedation on older patients: A single-centre randomized controlled trial.

AIMS: Advanced age is an important risk factor for adverse events during procedural sedation. Remimazolam is safe and effective in gastroscopic sedation. However, the ideal dose and application for older patients are not well known. We aim to investigate its 95% effective dose (ED95) for older patients undergoing gastroscopy and to assess its safety and efficacy, with propofol as the comparison. METHODS: The trial consists of 2 parts, patients aged >65 years and scheduled for outpatient painless gastroscopy were enrolled. In the first part, Dixon's up-and-down methodology was used to determine the ED95 of remimazolam besylate and propofol for gastroscopic insertion, in combination with 0.2 µg/kg remifentanil. In the second part, patients in each group received 0.2 µg/kg remifentanil and ED95 dose of the study drugs for sedation induction, supplemental doses were added to maintain sedation depth when necessary. The primary outcome was the incidence of adverse events. The secondary outcome was the recovery time. RESULTS: The ED95 of remimazolam besylate and propofol induction were 0.2039 (95% confidence interval 0.1753-0.3896) mg/kg and 1.9733 (95% confidence interval 1.7346-3.7021) mg/kg respectively. Adverse events were reported in 26 (40.6%) patients in the remimazolam group and 54 (83.1%) in the propofol group (P < .0001), whereas the remimazolam group presented a higher incidence of hiccups (P = .0169). Besides, the median time to awakening was approximately 1 min shorter with remimazolam than with propofol (P < .05). CONCLUSION: For older patients undergoing gastroscopy, the ED95 dose of remimazolam is a safer alternative than propofol when inducing the same sedation depth.

Combination of ultrasound-guided percutaneous A1 pulley release and intra-tendon sheath injection improves the therapeutic outcomes in adult trigger finger patients.

AIM: This study aimed to use high-frequency ultrasound guidance to compare the efficacy of percutaneous release combined with intra-tendon sheath injection (PR-ITSI) and percutaneous release only (PR-ONLY) in the treatment of adult trigger finger (TF) patients. MATERIALS AND METHODS: A total of 48 patients were randomly divided into PR-ITSI group and PR-ONLY group. The thickness of the A1 pulley was measured prior to surgery and 1-year after surgery. Visual Analogue Scale (VAS) score and Patient Global Impression of Improvement (PGI-I) scale score of affected fingers were evaluated at 1 day, 1 month, and 1 year after surgery. RESULTS: The overall difference of VAS score between the two groups after treatment was statistically significant (p<0.001), while the VAS scores gradually decreased in both groups at different time-points after treatment. The VAS scores in the PR-ITSI group at 1 day and 1 month after surgery were 1.475 and 0.904 (p<0.001), respectively, which were lower than those in the PR-ONLY group. Different treatment methods had no effect on the VAS score at 1 year after surgery (p=0.055). The thickness of the A1 pulley at 1 year after surgery was lower than that before surgery (p<0.001), whereas there was no significant difference in A1 pulley thickness between the two groups (p=0.095). The rate of PGI-I scale improvement by one grade at 1 day, 1 month, and 1 year after surgery in the PR-ITSI group was 15.322 times (95%CI: 4.466-52.573, p<0.001), 14.807 times (95%CI: 2.931-74.799, p=0.001), and 15.557 times (95%CI: 1.119-216.307, p=0.041), respectively, than that in the PR-ONLY group. CONCLUSION: Ultrasound-guided PR-ITSI is superior to PR-ONLY in the VAS score and PGI-I scale for adult TF patients.

A novel CEST-contrast nanoagent for differentiating the malignant degree in breast cancer.

Different subtypes of breast cancer (BCC) have variable degrees of malignancy, which is closely related to their extracellular pH (pHe). Therefore, it is increasingly significant to monitor the extracellular pH sensitively to further determine the malignancy of different subtypes of BCC. Here, a l-arginine and Eu3+ assembled nanoparticle Eu3+@l-Arg was prepared to detect the pHe of two breast cancer models (TUBO is non-invasive and 4T1 is malignant) using a clinical chemical exchange saturation shift imaging technique. The experiments in vivo showed that Eu3+@l-Arg nanomaterials could respond sensitively to changes of pHe. In 4T1 models, the CEST signal enhanced about 5.42 times after Eu3+@l-Arg nanomaterials were used to detect the pHe. In contrast, few enhancements of the CEST signal were seen in the TUBO models. This significant difference had led to new ideas for identifying subtypes of BCC with different degrees of malignancy.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning.

BACKGROUND: Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children. It is associated with high rates of morbidity and mortality, and rapid detection and administration of antimicrobials have been emphasized. The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness. METHODS: Three gene expression datasets were available from the Gene Expression Omnibus collection. First, the differentially expressed genes (DEGs) were found with the use of the R program, and then gene set enrichment analysis was carried out. Subsequently, the DEGs were combined with the major module genes chosen using the weighted gene co-expression network. The hub genes were identified by the use of three machine-learning algorithms: random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator. The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes. In addition, the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). The relationship between the diagnostic markers and infiltrating immune cells was further studied. RESULTS: Overall, after overlapping key module genes and DEGs, we detected 402 overlapping genes. As pediatric sepsis diagnostic indicators, CYSTM1 (AUC = 0.988), MMP8 (AUC = 0.973), and CD177 (AUC = 0.986) were investigated and demonstrated statistically significant differences (P < 0.05) and diagnostic efficacy in the validation set. As indicated by the immune cell infiltration analysis, multiple immune cells may be involved in the development of pediatric sepsis. Additionally, all diagnostic characteristics may correlate with immune cells to varying degrees. CONCLUSIONS: The candidate hub genes (CD177, CYSTM1, and MMP8) were identified, and the nomogram was constructed for pediatric sepsis diagnosis. Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

Laryngeal edema following remimazolam-induced anaphylaxis: a rare clinical manifestation.

BACKGROUND: Remimazolam is an ultra-short-acting intravenous benzodiazepine, which has been used as sedative/anesthetic in procedural sedation and anesthesia. Although peri-operative anaphylaxis due to remimazolam has been reported recently, the spectrum of the allergic reactions is still not fully known. CASE PRESENTATION: We describe a case of anaphylaxis following remimazolam administration in a male patient undergoing colonoscopy under procedural sedation. The patient presented complex clinical signs including airway changes, skin symptoms, gastrointestinal manifestations and hemodynamic fluctuations. Different from other reported cases, laryngeal edema was the initial and main clinical feature of remimiazolam-induced anaphylaxis. CONCLUSIONS: Remimazolam-induced anaphylaxis has a rapid onset and complex clinical features. This case reminds anesthesiologists should be particularly alert to the unknown adverse reactions of new anesthetics.

The impact of iron deposition on the fear circuit of the brain in patients with Parkinson's disease and anxiety.

Objective: Anxiety is one of the most common psychiatric symptoms of Parkinson's disease (PD), and brain iron deposition is considered to be one of the pathological mechanisms of PD. The objective of this study was to explore alterations in brain iron deposition in PD patients with anxiety compared to PD patients without anxiety, especially in the fear circuit. Methods: Sixteen PD patients with anxiety, 23 PD patients without anxiety, and 26 healthy elderly controls were enrolled prospectively. All subjects underwent neuropsychological assessments and brain magnetic resonance imaging (MRI) examinations. Voxel-based morphometry (VBM) was used to study morphological brain differences between the groups. Quantitative susceptibility mapping (QSM), an MRI technique capable of quantifying susceptibility changes in brain tissue, was used to compare susceptibility changes in the whole brain among the three groups. The correlations between brain susceptibility changes and anxiety scores quantified using the Hamilton Anxiety Rating Scale (HAMA) were compared and analyzed. Results: PD patients with anxiety had a longer duration of PD and higher HAMA scores than PD patients without anxiety. No morphological brain differences were observed between the groups. In contrast, voxel-based and ROI-based QSM analyses showed that PD patients with anxiety had significantly increased QSM values in the medial prefrontal cortex, anterior cingulate cortex, hippocampus, precuneus, and angular cortex. Furthermore, the QSM values of some of these brain regions were positively correlated with the HAMA scores (medial prefrontal cortex: r = 0.255, p = 0.04; anterior cingulate cortex: r = 0.381, p < 0.01; hippocampus: r = 0.496, p < 0.01). Conclusion: Our findings support the idea that anxiety in PD is associated with iron burden in the brain fear circuit, providing a possible new approach to explaining the potential neural mechanism of anxiety in PD.

Solute Carrier Family 7 Member 11 (SLC7A11) is a Potential Prognostic Biomarker in Uterine Corpus Endometrial Carcinoma.

Background: Uterine corpus endometrial carcinoma (UCEC) is a common type of gynecological cancers, second only to cervical cancer in incidence. Thus, it is necessary to develop effective therapies and identify biomarkers for its prognosis. Solute carrier family 7 member 11 (SLC7A11) is well known for its role in maintaining the intracellular glutathione level and preventing oxidative-stress-induced cell death. However, the association between SLC7A11 expression and prognosis as well as the correlation between tumor-infiltrating immune cells (TIICs) and immunotherapy of UCEC has rarely been reported. This study aims to evaluate the prognostic significance and immune cell infiltration level of SLC7A11 in UCEC. Methods: Bioinformatics analysis tools and databases, including R software, National Center for Biotechnology Information (NCBI), The Cancer Genome Atlas (TCGA), GEPIA2, Sangerbox, Kaplan-Meier (K-M) Plotter, TISIDB, and TIMER2, were utilized to measure the expression level and clarify the clinical significance of SLC7A11 in UCEC. Results: SLC7A11 expression was dramatically up-regulated in UCEC patients and associated with prognosis. DNA methylation levels in the SLC7A11-promoter region were significantly higher in normal participants than in patients with UCEC. We also showed that SLC7A11 overexpression was associated with TIICs, immune checkpoint blockers (ICBs), and immunotherapy response in UCEC. The half-maximal inhibitory concentration (IC50) results obtained with the cohort from TCGA showed that Z-VAD-FMK (Caspase inhibitor), S-Triphenylmethyl-L-cysteine (S-Trityl-L-cysteine), and TAE684 (ALK inhibitor) had higher IC50 values in low-expression patient (p < 0.05). Conclusion: SLC7A11 overexpression is associated with favorable prognosis of patients with UCEC and is associated with TIICs and the responses to immunotherapy.

Effects of Maternal Exercise Modes on Glucose and Lipid Metabolism in Offspring Stem Cells.

CONTEXT: Maternal exercise positively influences pregnancy outcomes and metabolic health in progeny; however, data regarding the effects of different modes of prenatal exercise on offspring metabolic phenotype is lacking. OBJECTIVE: To elucidate the effects of different modes of maternal exercise on offspring umbilical cord derived mesenchymal stem cell (MSC) metabolism. DESIGN: Randomized controlled trial. SETTING: Clinical research facility. PATIENTS: Healthy females between 18 and 35 years of age and <16 weeks' gestation. INTERVENTION: Women were randomized to either 150 minutes of moderate intensity aerobic, resistance (RE), or combination exercise per week or to a non-exercising control. MAIN OUTCOME MEASURES: At delivery, MSCs were isolated from the umbilical cords. MSC glucose and fatty acid(s) metabolism was assessed using radiolabeled substrates. RESULTS: MSCs from offspring of all the exercising women demonstrated greater partitioning of oleate (P ≤ 0.05) and palmitate (P ≤ 0.05) toward complete oxidation relative to non-exercisers. MSCs from offspring of all exercising mothers also had lower rates of incomplete fatty acid oxidation (P ≤ 0.05), which was related to infant adiposity at 1 month of age. MSCs from all exercising groups exhibited higher insulin-stimulated glycogen synthesis rates (P ≤ 0.05), with RE having the largest effect (P ≤ 0.05). RE also had the greatest effect on MSC glucose oxidation rates (P ≤ 0.05) and partitioning toward complete oxidation (P ≤ 0.05). CONCLUSION: Our data demonstrates that maternal exercise enhances glucose and lipid metabolism of offspring MSCs. Improvements in MSC glucose metabolism seem to be the greatest with maternal RE. Clinical Trial: ClinicalTrials.gov Identifier: NCT03838146.

TREM2hi resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis.

Sepsis-induced cardiomyopathy (SICM) is common in septic patients with a high mortality and is characterized by an abnormal immune response. Owing to cellular heterogeneity, understanding the roles of immune cell subsets in SICM has been challenging. Here we identify a unique subpopulation of cardiac-resident macrophages termed CD163+RETNLA+ (Mac1), which undergoes self-renewal during sepsis and can be targeted to prevent SICM. By combining single-cell RNA sequencing with fate mapping in a mouse model of sepsis, we demonstrate that the Mac1 subpopulation has distinct transcriptomic signatures enriched in endocytosis and displays high expression of TREM2 (TREM2hi). TREM2hi Mac1 cells actively scavenge cardiomyocyte-ejected dysfunctional mitochondria. Trem2 deficiency in macrophages impairs the self-renewal capability of the Mac1 subpopulation and consequently results in defective elimination of damaged mitochondria, excessive inflammatory response in cardiac tissue, exacerbated cardiac dysfunction and decreased survival. Notably, intrapericardial administration of TREM2hi Mac1 cells prevents SICM. Our findings suggest that the modulation of TREM2hi Mac1 cells could serve as a therapeutic strategy for SICM.

Prediction of postoperative infection in elderly using deep learning-based analysis: an observational cohort study.

Elderly patients are susceptible to postoperative infections with increased mortality. Analyzing with a deep learning model, the perioperative factors that could predict and/or contribute to postoperative infections may improve the outcome in elderly. This was an observational cohort study with 2014 elderly patients who had elective surgery from 28 hospitals in China from April to June 2014. We aimed to develop and validate deep learning-based predictive models for postoperative infections in the elderly. 1510 patients were randomly assigned to be training dataset for establishing deep learning-based models, and 504 patients were used to validate the effectiveness of these models. The conventional model predicted postoperative infections was 0.728 (95% CI 0.688-0.768) with the sensitivity of 66.2% (95% CI 58.2-73.6) and specificity of 66.8% (95% CI 64.6-68.9). The deep learning model including risk factors relevant to baseline clinical characteristics predicted postoperative infections was 0.641 (95% CI 0.545-0.737), and sensitivity and specificity were 34.2% (95% CI 19.6-51.4) and 88.8% (95% CI 85.6-91.6), respectively. Including risk factors relevant to baseline variables and surgery, the deep learning model predicted postoperative infections was 0.763 (95% CI 0.681-0.844) with the sensitivity of 63.2% (95% CI 46-78.2) and specificity of 80.5% (95% CI 76.6-84). Our feasibility study indicated that a deep learning model including risk factors for the prediction of postoperative infections can be achieved in elderly. Further study is needed to assess whether this model can be used to guide clinical practice to improve surgical outcomes in elderly.

Assessment of the Velopharyngeal Mechanism at Rest and During Speech in Children With 22q11.2DS: A Cross-Sectional Study.

OBJECTIVE: Velopharyngeal dysfunction (VPD) associated with 22q11.2 deletion syndrome (22q11.2DS) has a complex etiology. This study had 3 aims: (1) assess differences in velopharyngeal and levator muscle configuration during rest versus sustained speech production (2) compare differences in velopharyngeal changes between children with and without 22q11.2DS (3) examine the relationship between adenoid thickness, pharyngeal depth, and velopharyngeal changes. DESIGN: Cross-sectional. METHODS: A total of 22 participants, 11 with 22q11.2DS and 11 controls with normal speech and velopharyngeal anatomy (ages 4-12 years), underwent nonsedated MRI at rest and during sustained /i/. Differences in velar and levator muscle contraction across the 2 different conditions were analyzed, using matched paired t-tests. Mean differences across participant groups were examined. Correlation analyses were also conducted. RESULTS: When comparing differences between rest and sustained phoneme production (aim 1), significant (P < .05) differences were noted for all velar and levator muscle variables. For differences in velopharyngeal changes between children with and without 22q11.2DS (aim 2), VP ratio and effective VP ratio were noted to be significantly different. Pharyngeal depth and adenoid thickness were correlated with velar and levator muscle change measures and ratios (aim 3). CONCLUSION: Results from this study provide quantitative in vivo measurements of the contracted levator muscle and velum in young children with 22q11.2DS. Results demonstrated that VP ratio and EVP ratio are significantly different between children with and without 22q11.2DS and that pharyngeal depth is a strong clinical determinant of VPD in children with 22q11.2DS.

[Improvement effect of Shegan Mahuang Decoction on rats with cold-induced asthma based on TRPV1/NRF-1/mtTFA pathway].

This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 ℃, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.

Mining Potential Drug Targets and Constructing Diagnostic Models for Heart Failure Based on miRNA-mRNA Networks.

Heart failure (HF) is a globally prevalent cardiovascular disease, but effective drug targets and diagnostic models are still lacking. This study was designed to investigate effective drug targets and diagnostic models for HF in terms of miRNA targets, hoping to contribute to the understanding and treatment of HF. Using HF miRNA and gene expression profile data from the GEO database, we analyzed differentially expressed miRNAs/gene identification in HF using Limma and predicted miRNA targets by the online TargetScan database. Subsequently, gene set enrichment analysis and annotation were performed using WebGestaltR package. Protein-protein interactions were identified using the STRING database. The proximity of drugs to treat HF was also calculated and predicted for potential target therapeutic drug. In addition, further drug identification was performed by molecular docking. Finally, diagnostic models were constructed based on differential miRNAs. The GEO dataset was used to screen 66 differentially expressed miRNAs, incorporating 56 downregulated miRNAs and 10 upregulated miRNAs. The JAK-STAT signaling pathway, MAPK signaling pathway, p53 signaling pathway, Prolactin signaling pathway, and TGF-beta signaling pathway were enriched, as shown by KEGG enrichment analysis on the target genes. In addition, we found that 83 genes were upregulated and 92 genes were downregulated in HF patients vs. healthy individuals. Based on the inflammation-related score, hypoxia-related score, and energy metabolism-related score, we identified key miRNA-mRNA pairs and constructed an interaction network. Following that, TAP1, which had the highest expression and network connectivity in acute HF with crystal and molecular docking studies, was selected as a key candidate gene in the network. And the compound DB04847 was selected to produce a large number of favorable interactions with TAP1 protein. Finally, we constructed two diagnostic models based on the differential miRNAs hsa-miR-6785-5p and hsa-miR-4443. In conclusion, we identified TAP1, a key candidate gene in the diagnosis and treatment of HF, and determined that compound DB04847 is highly likely to be a potential inhibitor of TAP1. The TAP1 gene was also found to be regulated by hsa-miR-6785-5p and hsa-miR-4443, and a diagnostic model was constructed. This provides a new promising direction to improve the diagnosis, prognosis, and treatment outcome and guide more effective immunotherapy strategies of HF.