Efficacy of erector spinae plane block for postoperative analgesia after liver surgeries: a systematic review and meta-analysis.

BACKGROUND: Data on the effectiveness of erector spinae plane block (ESPB) for patients undergoing liver surgeries is limited and inconclusive. We hereby aimed to systematically review if ESPB can provide adequate analgesia after liver surgery. METHODS: PubMed, CENTRAL, Scopus, Embase, and gray literature were examined up to 25th April 2023 for randomized controlled trials (RCTs) comparing ESPB with control or spinal analgesia. RESULTS: Nine RCTs were included of which three compared ESPB with spinal analgesia. 24-hour opioid consumption did not differ significantly between ESPB vs. control (MD: -35.25 95% CI: -77.01, 6.52 I2 = 99%) or ESPB vs. spinal analgesia (MD: 2.32 95% CI: -6.12, 10.77 I2 = 91%). Comparing pain scores between ESPB and control, a small but significant effect favoring ESPB was noted at 12 h and 48 h, but not at 6-8 h and 24 h. Pain scores did not differ between ESPB and spinal analgesia. The risk of postoperative nausea and vomiting was also not significantly different between ESPB vs. control or spinal analgesia. GRADE assessment shows moderate certainty of evidence. CONCLUSION: ESPB may not provide any significant postoperative analgesia in liver surgery patients. There was a tendency of reduced opioid consumption with ESPB. Limited data also showed that ESPB and spinal analgesia had no difference in pain scores and 24-hour analgesic consumption.

Biomarkers in the prediction of complications in pregnancy after assisted reproductive technology.

OBJECTIVES: To compare the temporal changes in mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) across gestation between assisted reproductive technology (ART) pregnancies complicated with great obstetrical syndromes (GOS) or gestational diabetes (GDM) ± large-for-gestational-age (LGA) fetus, and uncomplicated ART pregnancies. METHODS: This was a prospective longitudinal study of 143 women with singleton pregnancies who conceived through ART at the Department of Obstetrics and Gynecology, Prince of Wales Hospital, the Chinese University of Hong Kong, Hong Kong SAR between December 2017 and January 2020. The participants were followed up at 6-6+3, 11-13+6, 20-24+6, 30-34+6, and 35-37+6 weeks for the measurement of MAP, UtA-PI, PlGF, and sFlt-1. A linear mixed-effects analysis was performed to compare the biomarkers in the GOS, GDM ± LGA, and uncomplicated groups across gestation. RESULTS: Thirty-three (23.1%) and fifty-five (31.5%) women were diagnosed with GOS and GDM ± LGA, respectively. The GOS group had higher estimated marginal mean log10 MAP mulitples of the median (MoM) across gestation, compared with the uncomplicated group (0.00771 vs -0.02022; P < 0.001), when adjusting for clinical visits and days of embryo transfer. The absolute mean log10 MAP MoM in the GOS group was found to be significantly higher than that of the uncomplicated group at all clinical visits from 6 weeks onwards. Furthermore, the estimated marginal mean log10 PlGF MoM was significantly lower in the GOS group across gestation, compared with the uncomplicated group (-0.04226 vs 0.05566; P = 0.010). The significant difference in log10 PlGF MoM was observed from 11-13+6 to 30-34+6 week of gestation (P < 0.05). However, no significant differences in the estimated marginal means of log10 UtA-PI MoM and log10 sFlt-1 MoM between GOS and uncomplicated groups were observed. GDM ± LGA group had a lower estimated marginal mean log10 PlGF MoM throughout pregnancy compared with the uncomplicated group (-0.01536 vs 0.05572; P = 0.032). In the individual visit analysis, the significant difference was observed at the 20-24+6 and 35-37+6 weeks visits (P < 0.05). There were no significant differences in estimated marginal mean log10 MoM of MAP, UtA-PI, and sFlt-1 between GDM ± LGA and uncomplicated groups during pregnancy. CONCLUSION: Our study has revealed that among pregnancies conceived through ART, GOS is associated with higher MAP and lower PlGF from early gestation until late third trimester, while GDM ± LGA is associated with lower PlGF during the second half of pregnancy. The same degree of differences in MAP and PlGF persists from early until late gestation in the GOS group and these findings highlight the importance of early screening during the first trimester to identify women who are at risk for developing GOS following ART procedures. Lastly, the potential of PlGF in predicting the development of GDM from the second trimester of pregnancy requires further investigation.

ZIF-67 and Biomass-Derived N, S-Codoped Activated Carbon Composite Derivative for High-Effective Removal of Hydroquinone from Water.

Hydroquinone (HQ) in wastewater is of great concern, as it is harmful to human health and threatens the ecological environment. However, the existing adsorbents have low adsorption capacity for HQ. To improve the removal of HQ, N,S-codoped activated carbon-ZIF-67 (NSAC-ZIF-67@C) was synthesized in this study by in situ growth of ZIF-67 on N,S-codoped activated carbon (NSAC) and carbonization. The influence of pH, contact time, and initial concentration on the adsorption behaviors of NSAC-ZIF-67@C on HQ were investigated. Owing to the synergistic effect of abundant active sites and well-developed pore structure, the NSAC-ZIF-67@C achieved a prominent adsorption capacity of 962 mg·g-1 and can still retain high adsorption performance after 5 cycles for HQ, which is superior to that of reported other adsorbents. HQ adsorption follows the pseudo-second-order kinetics model (R2 = 0.99999) and the Freundlich isotherm model. X-ray photoelectron spectroscopy (XPS) analysis before and after adsorption as well as density functional theory (DFT) calculation results showed that pyridinic-N-termini were conducive to the π-π interactions and hydrogen-bonding interactions. Therefore, the adsorption mechanisms of NSAC-ZIF-67@C on HQ involve pore filling, electrostatic attraction, π-π interaction, and hydrogen bonding. This study is expected to provide a reference for designing highly effective adsorbents for wastewater treatment.

Correlation between islet α cell function and peripheral neuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated. RESULTS: There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients. CONCLUSION: Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.

Temperature-compensated high strain measurement based on a Fabry-Perot interferometer with the virtual-assisted Vernier effect.

A highly sensitive optical fiber Fabry-Perot interferometer (FPI) for strain measurement with temperature compensation is proposed. Instead of using another actual reference interferometer, a virtual FPI is constructed to superpose with the sensing FPI to form the Vernier effect. The fundamental and the first-order harmonic Vernier effect are generated to increase the sensitivity by adjusting the parameter of the virtual FPI. In order to separate the strain from the environment temperature, an FBG is cascaded to distinguish the applied temperature. Experimental results demonstrate that, with the help of the fundamental Vernier effect, the sensitivity and temperature of the FPI increases from 1.05 pm/°C to 10.63 pm/°C in the temperature range of 40-120°C, and the sensitivity of strain increases from 2.635 pm/µÎµ to 33.11 pm/µÎµ in the strain range of 0-400 µÎµ. In order to access the tracking points more easily and further enhance the sensitivities, the first-order harmonic Vernier effect is generated by modifying the virtual FPI. Results show that the temperature and strain sensitivities are 21.25 pm/°C and 62.25 pm/µÎµ, respectively. In addition, with the help of the FBG, the strain can be separated from the temperature by solving the cross-sensitivity matrix.

DL-3-n-Butylphthalide Ameliorates Post-stroke Emotional Disorders by Suppressing Neuroinflammation and PANoptosis.

Post-stroke emotional disorders such as post-stroke anxiety and post-stroke depression are typical symptoms in patients with stroke. They are closely associated with poor prognosis and low quality of life. The State Food and Drug Administration of China has approved DL-3-n-butylphthalide (NBP) as a treatment for ischemic stroke (IS). Clinical research has shown that NBP alleviates anxiety and depressive symptoms in patients with IS. Therefore, this study explored the role and molecular mechanisms of NBP in cases of post-stroke emotional disorders using network pharmacology and experimental validation. The results showed that NBP treatment significantly increased the percentage of time spent in the center of the middle cerebral artery occlusion (MCAO) rats in the open field test and the percentage of sucrose consumption in the sucrose preference test. Network pharmacology results suggest that NBP may regulate neuroinflammation and cell death. Further experiments revealed that NBP inhibited the toll-like receptor 4/nuclear factor kappa B signaling pathway, decreased the level of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, and interleukin-6, and M1-type microglia markers (CD68, inducible nitric oxide synthase), and reduced the expression of PANoptosis-related molecules including caspase-1, caspase-3, caspase-8, gasdermin D, and mixed lineage kinase domain-like protein in the hippocampus of the MACO rats. These findings demonstrate that the mechanisms through which NBP ameliorates post-stroke emotional disorders in rats are associated with inhibiting neuroinflammation and PANoptosis, providing a new strategy and experimental basis for treating post-stroke emotional disorders.

Challenges and Suggestions of Ethical Review on Clinical Research Involving Brain-Computer Interfaces.

Brain-computer interface (BCI) technology is rapidly advancing in medical research and application. As an emerging biomedical engineering technology, it has garnered significant attention in the clinical research of brain disease diagnosis and treatment, neurological rehabilitation, and mental health. However, BCI also raises several challenges and ethical concerns in clinical research. In this article, the authors investigate and discuss three aspects of BCI in medicine and healthcare: the state of international ethical governance, multidimensional ethical challenges pertaining to BCI in clinical research, and suggestive concerns for ethical review. Despite the great potential of frontier BCI research and development in the field of medical care, the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI. To ensure "responsible innovation" in BCI research in healthcare and medicine, the creation of an ethical global governance framework and system, along with special guidelines for cutting-edge BCI research in medicine, is suggested.

Mangiferin alleviated poststroke cognitive impairment by modulating lipid metabolism in cerebral ischemia/reperfusion rats.

INTRODUCTION: Mangiferin is a Chinese herbal extract with multiple biological activities. Mangiferin can penetrate the blood‒brain barrier and has potential in the treatment of nervous system diseases. These findings suggest that mangiferin protects the neurological function in ischemic stroke rats by targeting multiple signaling pathways. However, little is known about the effect and mechanism of mangiferin in alleviating poststroke cognitive impairment. METHODS: Cerebral ischemia/reperfusion (I/R) rats were generated via middle cerebral artery occlusion. Laser speckle imaging was used to monitor the cerebral blood flow. The I/R rats were intraperitoneally (i.p.) injected with 40 mg/kg mangiferin for 7 consecutive days. Neurological scoring, and TTC staining were performed to evaluate neurological function. Behavioral experiments, including the open field test, elevated plus maze, sucrose preference test, and novel object recognition test, were performed to evaluate cognitive function. Metabolomic data from brain tissue with multivariate statistics were analyzed by gas chromatography‒mass spectrometry and liquid chromatography‒mass spectrometry. RESULTS: Mangiferin markedly decreased neurological scores, and reduced infarct areas. Mangiferin significantly attenuated anxiety-like and depression-like behaviors and enhanced learning and memory in I/R rats. According to the metabolomics results, 13 metabolites were identified to be potentially regulated by mangiferin, and the differentially abundant metabolites were mainly involved in lipid metabolism. CONCLUSIONS: Mangiferin protected neurological function and relieved poststroke cognitive impairment by improving lipid metabolism abnormalities in I/R rats.

Microglial activation in the medial prefrontal cortex after remote fear recall participates in the regulation of auditory fear extinction.

Excessive or inappropriate fear responses can lead to anxiety-related disorders, such as post-traumatic stress disorder (PTSD). Studies have shown that microglial activation occurs after fear conditioning and that microglial inhibition impacts fear memory. However, the role of microglia in fear memory recall remains unclear. In this study, we investigated the activated profiles of microglia after the recall of remote-cued fear memory and the role of activated microglia in the extinction of remote-cued fear in adult male C57BL/6 mice. The results revealed that the expression of the microglia marker Iba1 increased in the medial prefrontal cortex (mPFC) at 10 min and 1 h following remote-cued fear recall, which was accompanied by amoeboid morphology. Inhibiting microglial activation through PLX3397 treatment before remote fear recall did not affect recall, reconsolidation, or regular extinction but facilitated recall-extinction and mitigated spontaneous recovery. Moreover, our results demonstrated reduced co-expression of Iba1 and postsynaptic density protein 95 (PSD95) in the mPFC, along with decreases in the p-PI3K/PI3K ratio, p-Akt/Akt ratio, and KLF4 expression after PLX3397 treatment. Our results suggest that microglial activation after remote fear recall impedes fear extinction through the pruning of synapses in the mPFC, accompanied by alterations in the expression of the PI3K/AKT/KLF4 pathway. This finding can help elucidate the mechanism involved in remote fear extinction, contributing to the theoretical foundation for the intervention and treatment of PTSD.

Efficacy of Huangma Ding or autologous platelet-rich gel for the diabetic lower extremity arterial disease patients with foot ulcers.

BACKGROUND: Diabetes foot is one of the most serious complications of diabetes and an important cause of death and disability, traditional treatment has poor efficacy and there is an urgent need to develop a practical treatment method. AIM: To investigate whether Huangma Ding or autologous platelet-rich gel (APG) treatment would benefit diabetic lower extremity arterial disease (LEAD) patients with foot ulcers. METHODS: A total of 155 diabetic LEAD patients with foot ulcers were enrolled and divided into three groups: Group A (62 patients; basal treatment), Group B (38 patients; basal treatment and APG), and Group C (55 patients; basal treatment and Huangma Ding). All patients underwent routine follow-up visits for six months. After follow-up, we calculated the changes in all variables from baseline and determined the differences between groups and the relationships between parameters. RESULTS: The infection status of the three groups before treatment was the same. Procalcitonin (PCT) improved after APG and Huangma Ding treatment more than after traditional treatment and was significantly greater in Group C than in Group B. Logistic regression analysis revealed that PCT was positively correlated with total amputation, primary amputation, and minor amputation rates. The ankle-brachial pressure and the transcutaneous oxygen pressure in Groups B and C were greater than those in Group A. The major amputation rate, minor amputation rate, and total amputation times in Groups B and C were lower than those in Group A. CONCLUSION: Our research indicated that diabetic foot ulcers (DFUs) lead to major amputation, minor amputation, and total amputation through local infection and poor microcirculation and macrocirculation. Huangma Ding and APG were effective attreating DFUs. The clinical efficacy of Huangma Ding was better than that of autologous platelet gel, which may be related to the better control of local infection by Huangma Ding. This finding suggested that in patients with DFUs combined with coinfection, controlling infection is as important as improving circulation.

Ultrasonographic placental parameters at 11-13+6 weeks' gestation in the prediction of complications in pregnancy after assisted reproductive technology.

OBJECTIVE: To evaluate the performance of maternal factors, biophysical and biochemical markers at 11-13 + 6 weeks' gestation in the prediction of gestational diabetes mellitus with or without large for gestational age (GDM ± LGA) fetus and great obstetrical syndromes (GOS) among singleton pregnancy following in-vitro fertilisation (IVF)/embryo transfer (ET). MATERIALS AND METHODS: A prospective cohort study was conducted between December 2017 and January 2020 including patients who underwent IVF/ET. Maternal mean arterial pressure (MAP), ultrasound markers including placental volume, vascularisation index (VI), flow index (FI) and vascularisation flow index (VFI), mean uterine artery pulsatility index (mUtPI) and biochemical markers including placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 11-13 + 6 weeks' gestation. Logistic regression analysis was performed to determine the significant predictors of complications. RESULTS: Among 123 included pregnancies, 38 (30.9%) had GDM ± LGA fetus and 28 (22.8%) had GOS. The median maternal height and body mass index were significantly higher in women with GDM ± LGA fetus. Multivariate logistic regression analysis demonstrated that in the prediction of GDM ± LGA fetus and GOS, there were significant independent contributions from FI MoM (area under curve (AUROC) of 0.610, 95% CI 0.492-0.727; p = 0.062) and MAP MoM (AUROC of 0.645, 95% CI 0.510-0.779; p = 0.026), respectively. CONCLUSION: FI and MAP are independent predictors for GDM ± LGA fetus and GOS, respectively. However, they have low predictive value. There is a need to identify more specific novel biomarkers in differentiating IVF/ET pregnancies that are at a higher risk of developing complications.

Nonparametric two-sample tests of high dimensional mean vectors via random integration.

Testing the equality of the means in two samples is a fundamental statistical inferential problem. Most of the existing methods are based on the sum-of-squares or supremum statistics. They are possibly powerful in some situations, but not in others, and they do not work in a unified way. Using random integration of the difference, we develop a framework that includes and extends many existing methods, especially in high-dimensional settings, without restricting the same covariance matrices or sparsity. Under a general multivariate model, we can derive the asymptotic properties of the proposed test statistic without specifying a relationship between the data dimension and sample size explicitly. Specifically, the new framework allows us to better understand the test's properties and select a powerful procedure accordingly. For example, we prove that our proposed test can achieve the power of 1 when nonzero signals in the true mean differences are weakly dense with nearly the same sign. In addition, we delineate the conditions under which the asymptotic relative Pitman efficiency of our proposed test to its competitor is greater than or equal to 1. Extensive numerical studies and a real data example demonstrate the potential of our proposed test.

Status quo and influencing factors of multiprofessional and multidisciplinary teamwork for early mobilization in mechanically ventilated patients in ICUs: A multi-centre survey study.

AIM: To understand the status quo of multiprofessional and multidisciplinary collaboration for early mobilization of mechanically ventilated patients in Chinese ICUs and identify any factors that may influence this practice. DESIGN: A multi-centre cross-sectional survey. METHODS: From October to November 2022, the convenience sampling method was used to select ICU multiprofessional and multidisciplinary early mobility members (including physicians, nurses and physiotherapists) from 27 tertiary general hospitals in 14 provinces, cities and autonomous regions of China. They were asked to complete an author-developed questionnaire on the status of collaboration and the Assessment of Inter-professional Team Collaboration Scale. A multiple linear regression model was used to analyse the factors associated with the level of collaboration. RESULTS: Physicians, nurses and physiotherapists mostly suffered from the lack of normative protocols, unclear division of responsibilities and unclear multiprofessional and multidisciplinary teams when using a collaborative approach to early activities. Multiple linear regression analysis showed that the number of ICU patients managed, the existence of norms and processes, the attitude of colleagues around them, the establishment of a team, communication methods and activity leaders were significant influences on the level of collaboration among members of the multiprofessional and multidisciplinary early activities. CONCLUSION: The collaboration of multiprofessional and multidisciplinary early activity members for mechanically ventilated patients in the ICU remains unclear, and the collaboration strategy needs to be constructed and improved, taking into account China's human resources and each region's economic development level. IMPACT: This study investigates the collaboration status of multiprofessional and multidisciplinary activity members from the perspective of teamwork, analyses the reasons affecting the level of collaboration and helps to develop better teamwork strategies to facilitate the implementation of early activities. PATIENT OR PUBLIC CONTRIBUTION: The participants in this study were multiprofessional and multidisciplinary medical staff who performed early activities for ICU patients.

Effects of the High-Intensity Early Mobilization on Long-Term Functional Status of Patients with Mechanical Ventilation in the Intensive Care Unit.

Objective: Intensive care unit (ICU)-acquired weakness often occurs in patients with invasive mechanical ventilation (IMV). Early active mobility may reduce ICU-acquired weakness, improve functional status, and reduce disability. The aim of this study was to investigate whether high-intensity early mobility improves post-ICU discharge functional status of IMV patients. Methods: 132 adult patients in the ICU who were undergoing IMV were randomly assigned into two groups with a ratio of 1 : 1, with one group received high-intensity early mobility (intervention group, IG), while the other group received conventional treatment (control group, CG). The functional status (Barthel Index (BI)), capacity of mobility (Perme score and ICU Mobility Scale (IMS)), muscle strength (Medical Research Council sum scores (MRC-SS)), mortality, complication, length of ICU stay, and duration of IMV were evaluated at ICU discharge or after 3-month of ICU discharge. Results: The patient's functional status was improved (BI scores 90.6 ± 18.0 in IG vs. 77.7 ± 27.9 in CG; p=0.005), and capacity of mobility was increased (Perme score 17.6 ± 7.1 in IG vs. 12.2 ± 8.5 in CG, p < 0.001; IMS 4.7 ± 2.6 in IG vs. 3.0 ± 2.6 in CG, p < 0.001). The IG had a higher muscle strength and lower incidence of ICU-acquired weakness (ICUAW) than that in the CG. The incidence of mortality and delirium was also lower than CG at ICU discharge. However, there were no differences in terms of length of ICU stay, duration of IMV, ventilator-associated pneumonia, and venous thrombosis. Conclusions: High-intensity early mobility improved the patient's functional status and increased capacity of mobility with IMV. The benefits to functional status remained after 3 month of ICU discharge. Other benefits included higher muscle strength, lower incidence of ICUAW, mortality, and delirium in IG.

Enhancing Retinal Fundus Image Quality Assessment With Swin-Transformer-Based Learning Across Multiple Color-Spaces.

Purpose: The assessment of retinal image (RI) quality holds significant importance in both clinical trials and large datasets, because suboptimal images can potentially conceal early signs of diseases, thereby resulting in inaccurate medical diagnoses. This study aims to develop an automatic method for Retinal Image Quality Assessment (RIQA) that incorporates visual explanations, aiming to comprehensively evaluate the quality of retinal fundus images (RIs). Methods: We developed an automatic RIQA system, named Swin-MCSFNet, utilizing 28,792 RIs from the EyeQ dataset, as well as 2000 images from the EyePACS dataset and an additional 1,000 images from the OIA-ODIR dataset. After preprocessing, including cropping black regions, data augmentation, and normalization, a Swin-MCSFNet classifier based on the Swin-Transformer for multiple color-space fusion was proposed to grade the quality of RIs. The generalizability of Swin-MCSFNet was validated across multiple data centers. Additionally, for enhanced interpretability, a Score-CAM-generated heatmap was applied to provide visual explanations. Results: Experimental results reveal that the proposed Swin-MCSFNet achieves promising performance, yielding a micro-receiver operating characteristic (ROC) of 0.93 and ROC scores of 0.96, 0.81, and 0.96 for the "Good," "Usable," and "Reject" categories, respectively. These scores underscore the accuracy of RIQA based on Swin-MCSF in distinguishing among the three categories. Furthermore, heatmaps generated across different RIQA classification scores and various color spaces suggest that regions in the retinal images from multiple color spaces contribute significantly to the decision-making process of the Swin-MCSFNet classifier. Conclusions: Our study demonstrates that the proposed Swin-MCSFNet outperforms other methods in experiments conducted on multiple datasets, as evidenced by the superior performance metrics and insightful Score-CAM heatmaps. Translational Relevance: This study constructs a new retinal image quality evaluation system, which will contribute to the subsequent research of retinal images.

Identifying of immune-associated genes for assessing the obesity-associated risk to the offspring in maternal obesity: A bioinformatics and machine learning.

BACKGROUND: Perinatal exposure to maternal obesity predisposes offspring to develop obesity later in life. Immune dysregulation in the hypothalamus, the brain center governing energy homeostasis, is pivotal in obesity development. This study aimed to identify key candidate genes associated with the risk of offspring obesity in maternal obesity. METHODS: We obtained obesity-related datasets from the Gene Expression Omnibus (GEO) database. GSE135830 comprises gene expression data from the hypothalamus of mouse offspring in a maternal obesity model induced by a high-fat diet model (maternal high-fat diet (mHFD) group and maternal chow (mChow) group), while GSE127056 consists of hypothalamus microarray data from young adult mice with obesity (high-fat diet (HFD) and Chow groups). We identified differentially expressed genes (DEGs) and module genes using Limma and weighted gene co-expression network analysis (WGCNA), conducted functional enrichment analysis, and employed a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to pinpoint candidate hub genes for diagnosing obesity-associated risk in offspring of maternal obesity. We constructed a nomogram receiver operating characteristic (ROC) curve to evaluate the diagnostic value. Additionally, we analyzed immune cell infiltration to investigate immune cell dysregulation in maternal obesity. Furthermore, we verified the expression of the candidate hub genes both in vivo and in vitro. RESULTS: The GSE135830 dataset revealed 2868 DEGs between the mHFD offspring and the mChow group and 2627 WGCNA module genes related to maternal obesity. The overlap of DEGs and module genes in the offspring with maternal obesity in GSE135830 primarily enriched in neurodevelopment and immune regulation. In the GSE127056 dataset, 133 DEGs were identified in the hypothalamus of HFD-induced adult obese individuals. A total of 13 genes intersected between the GSE127056 adult obesity DEGs and the GSE135830 maternal obesity module genes that were primarily enriched in neurodevelopment and the immune response. Following machine learning, two candidate hub genes were chosen for nomogram construction. Diagnostic value evaluation by ROC analysis determined Sytl4 and Kncn2 as hub genes for maternal obesity in the offspring. A gene regulatory network with transcription factor-miRNA interactions was established. Dysregulated immune cells were observed in the hypothalamus of offspring with maternal obesity. Expression of Sytl4 and Kncn2 was validated in a mouse model of hypothalamic inflammation and a palmitic acid-stimulated microglial inflammation model. CONCLUSION: Two candidate hub genes (Sytl4 and Kcnc2) were identified and a nomogram was developed to predict obesity risk in offspring with maternal obesity. These findings offer potential diagnostic candidate genes for identifying obesity-associated risks in the offspring of obese mothers.

A late eating midpoint is associated with increased risk of diabetic kidney disease: a cross-sectional study based on NHANES 2013-2020.

BACKGROUND: Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. METHODS: The National Health and Nutrition Examination Survey (2013-2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were the specific diagnostic criteria for DKD. RESULTS: In total, details of 2194 subjects with diabetes were collected for analysis. The overall population were divided into four subgroups based on the eating midpoint quartiles. The prevalence of DKD varied noticeably (P = 0.037) across the four categories. When comparing subjects in the second and fourth quartiles of eating midpoint to those in the first one, the odds ratios (ORs) of DKD were 1.31 (95% CI, 1.03 to 1.67) and 1.33 (95% CI, 1.05 to 1.70), respectively. And after controlling for potential confounders, the corresponding ORs of DKD in the second and fourth quartiles were 1.42 (95% CI, 1.07 to 1.90) and 1.39 (95% CI, 1.04 to 1.85), respectively. CONCLUSIONS: A strong correlation was found between an earlier eating midpoint and a reduced incidence of DKD. Eating early in the day may potentially improve renal outcomes in patients with diabetes.

Ultra-high b-value DWI accurately identifies isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas.

OBJECTIVES: To distinguish isocitrate dehydrogenase (IDH) genotypes and tumor subtypes of adult-type diffuse gliomas based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5) in 2021 using standard, high, and ultra-high b-value diffusion-weighted imaging (DWI). MATERIALS AND METHODS: This prospective study enrolled 70 patients with adult-type diffuse gliomas who underwent multiple b-value DWI. Apparent diffusion coefficient (ADC) values including ADCb500/b1000, ADCb500/b2000, ADCb500/b3000, ADCb500/b4000, ADCb500/b6000, ADCb500/b8000, and ADCb500/b10000 in tumor parenchyma (TP) and contralateral normal-appearing white matter (NAWM) were calculated. The ADC ratios of TP/NAWM were assessed for correlations with IDH genotypes, tumor subtypes, and Ki-67 status; diagnostic performances were compared. RESULTS: All ADCs were significantly higher in IDH mutant gliomas than in IDH wild-type gliomas (p < 0.01 for all); ADCb500/b8000 had the highest area under the curve (AUC) of 0.866. All ADCs were significantly lower in glioblastoma than in astrocytoma (p < 0.01 for all). ADCs other than ADCb500/b1000 were significantly lower in glioblastoma than in oligodendroglioma (p < 0.05 for all). ADCb500/b8000 and ADCb500/b10000 were significantly higher in oligodendroglioma than in astrocytoma (p = 0.034 and 0.023). The highest AUCs were 0.818 for ADCb500/b6000 when distinguishing glioblastoma from astrocytoma, 0.979 for ADCb500/b8000 and ADCb500/b10000 when distinguishing glioblastoma from oligodendroglioma, and 0.773 for ADCb500/b10000 when distinguishing astrocytoma from oligodendroglioma. Additionally, all ADCs were negatively correlated with Ki-67 status (p < 0.05 for all). CONCLUSION: Ultra-high b-value DWI can reliably separate IDH genotypes and tumor subtypes of adult-type diffuse gliomas using WHO CNS5 criteria. CLINICAL RELEVANCE STATEMENT: Ultra-high b-value diffusion-weighted imaging can accurately distinguish isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas, which may facilitate personalized treatment and prognostic assessment for patients with glioma. KEY POINTS: • Ultra-high b-value diffusion-weighted imaging can accurately distinguish subtle differences in water diffusion among biological tissues. • Ultra-high b-value diffusion-weighted imaging can reliably separate isocitrate dehydrogenase genotypes and tumor subtypes of adult-type diffuse gliomas. • Compared with standard b-value diffusion-weighted imaging, high and ultra-high b-value diffusion-weighted imaging demonstrate better diagnostic performances.

Biocompatible formulation of a hydrophobic antimicrobial peptide L30 through nanotechnology principles and its potential role in mouse pneumonia model infected with Staphylococcus aureus.

Hydrophobic antimicrobial peptide L30, a potential antibiotic candidate, has poor water solubility and hemolytic activity. Herein, a biocompatible nano-formulation composed of liposomes and dendritic mesoporous silica encapsulation (LDMSNs@L30) was constructed for L30 to solve the limits for its clinical development. The characterization, antimicrobial activity and therapeutic effect of LDMSNs@L30 on Staphylococcus aureus 9 (cfr+) infected mice models were investigated. LDMSNs@L30 displayed a smooth, spherical, and monodisperse nanoparticle with a hydrodynamic diameter of 177.40 nm, an encapsulation rate of 56.13%, a loading efficiency of 32.26%, a release rate of 66.5%, and effective slow-release of L30. Compared with free L30, the formulation could significantly increase the solubility of L30 in PBS with the maximum concentration from 8 µg/mL to 2.25 mg/mL and decrease the hemolytic activity of hydrophobic peptide L30 with the HC5 from 65.36 µg/mL to more than 500 µg/mL. The nano delivery system LDMSNs@L30 also exhibited higher therapeutic effects on mice models infected with S. aureus 9 (cfr+) than those of free L30 after 7 days of treatment by reducing the lung inflammation and the inflammatory cytokines levels in plasma, showing better health score and pulmonary pathological improvement. Our research suggests that nano-formulation can be expected to be a promising strategy for peptide drugs in therapeutic applications.

The bidirectional associations between sarcopenia-related traits and cognitive performance.

While many studies have sought to explore the degree to which sarcopenia-related traits are associated with cognitive performance, these studies have yielded contradictory results without any clear indication of the causality of such relationships. In efforts to better understand associations between sarcopenia-related traits and cognitive ability, a series of multivariate linear regression assessments were carried out upon datasets derived through the National Health and Nutrition Examination Survey (NHANES). Of these, cognitive performance was assessed by the Digit Symbol Substitution Test (DDST), the Consortium to Establish a Registry for Alzheimer's Disease Immediate Recall Test (CERAD-IR), Delayed Recall Test (CERAD-DR) and Animal Fluency Test (AFT). Causal relationships between the two were further inferred via a two-sample Mendelian randomization (MR) analysis approach. Sarcopenia-related traits considered in these assessments included walking speed, appendicular skeletal muscle mass (ASM), and hand grip strength (HGS). Walking speed, ASM, and HGS were all significantly independently related to cognitive scores following adjustment for covariates. MR assessments also identified that each 1-SD higher walking speed and appendicular lean mass were causally and respectively associated with a 0.34 [standard error (SE) = 0.09; p < 0.001)] standardized score higher and a 0.07 (SE = 0.01; p < 0.001) standardized score higher cognitive score, whereas a higher hand grip strength was positively associated with a better cognitive performance. Reverse MR assessments also yielded similar findings. These data suggest that lower walking speed, muscle strength, and muscle mass were all closely related to lower cognitive performance irrespective of gender, and that there may be a mutually reinforcing relationship among these variables.