Comparison between solid pseudopapillary neoplasms of the pancreas and pancreatic ductal adenocarcinoma with cystic changes using computed tomography.

BACKGROUND: Solid pseudopapillary neoplasms of the pancreas (SPN) share similar imaging findings with pancreatic ductal adenocarcinoma with cystic changes (PDAC with cystic changes), which may result in unnecessary surgery. AIM: To investigate the value of computed tomography (CT) in differentiation of SPN from PDAC with cystic changes. METHODS: This study retrospectively analyzed the clinical and imaging findings of 32 patients diagnosed with SPN and 14 patients diagnosed with PDAC exhibiting cystic changes, confirmed through pathological diagnosis. Quantitative and qualitative analysis was performed, including assessment of age, sex, tumor size, shape, margin, density, enhancement pattern, CT values of tumors, CT contrast enhancement ratios, "floating cloud sign," calcification, main pancreatic duct dilatation, pancreatic atrophy, and peripancreatic invasion or distal metastasis. Multivariate logistic regression analysis was used to identify relevant features to differentiate between SPN and PDAC with cystic changes, and receiver operating characteristic curves were obtained to evaluate the diagnostic performance of each variable and their combination. RESULTS: When compared to PDAC with cystic changes, SPN had a lower age (32 years vs 64 years, P < 0.05) and a slightly larger size (5.41 cm vs 3.90 cm, P < 0.05). SPN had a higher frequency of "floating cloud sign" and peripancreatic invasion or distal metastasis than PDAC with cystic changes (both P < 0.05). No significant difference was found with respect to sex, tumor location, shape, margin, density, main pancreatic duct dilatation, calcification, pancreatic atrophy, enhancement pattern, CT values of tumors, or CT contrast enhancement ratios between the two groups (all P > 0.05). The area under the receiver operating characteristic curve of the combination was 0.833 (95% confidence interval: 0.708-0.957) with 78.6% sensitivity, 81.3% specificity, and 80.4% accuracy in differentiation of SPN from PDAC with cystic changes. CONCLUSION: A larger tumor size, "floating cloud sign," and peripancreatic invasion or distal metastasis are useful CT imaging features that are more common in SPN and may help discriminate SPN from PDAC with cystic changes.

Case report: Near-fatal hypermagnesemia resulting from the use of Epsom salts in a patient with normal renal function.

Hypermagnesemia commonly occurs in patients with renal dysfunction. Diagnosing hypermagnesemia represents a challenge due to its rarity and the absence of routine monitoring of magnesium levels. Furthermore, the lack of awareness among clinicians regarding this uncommon condition frequently leads to delayed diagnoses. Few patients survive with a serum magnesium level exceeding 7 mmol/L. This article presents a case study of near-fatal hypermagnesemia resulting from the oral administration of Epsom salts in a patient with normal renal function. A 60-year-old female presented to the gastroenterology department on Oct. 6, 2023, with a 3-day history of black stools. She underwent subtotal gastrectomy in 2005 and has a stable history of nephrotic syndrome. To investigate the cause of her bleeding, electronic gastroscopy and colonoscopy were scheduled for Oct. 11, 2023. She experienced a sudden loss of consciousness 30 min after the ingestion of Epsom salts. The attending physician suspected a severe magnesium poisoning. She was promptly administered calcium gluconate, underwent tracheal intubation with ambu bag ventilation, and received early continuous renal replacement therapy (CRRT). Swift diagnosis and CRRT contributed to a reduction in her serum magnesium levels from an initial 8.71 mmol/L to 1.35 mmol/L, leading to a remarkable improvement in the toxic symptoms associated with hypermagnesemia. Subsequently, she was managed in the gastroenterology department, with gastroscopy revealing bleeding from the gastrointestinal anastomotic ulcer. Following conservative treatments including acid suppression, stomach protection, and hemostasis, her symptoms improved, and she was successfully discharged. This study aims to alert clinicians to the possibility of hypermagnesemia in individuals with normal renal function. Physicians should exercise caution when prescribing Epsom salts to patients with underlying gastrointestinal conditions. If necessary, alternative drug therapies may be considered to mitigate the risk of hypermagnesemia. Timely intervention is pivotal in averting life-threatening complications linked to hypermagnesemia.

Radial extracorporeal shockwave promotes osteogenesis-angiogenesis coupling of bone marrow stromal cells from senile osteoporosis via activating the Piezo1/CaMKII/CREB axis.

Radial extracorporeal shockwave (r-ESW) and bone marrow stromal cells (BMSCs) have been reported to alleviate senile osteoporosis (SOP), but its regulatory mechanism remains unclear. In this study, we firstly isolated human BMSCs from bone marrow samples and treated with varying r-ESW doses. And we found that r-ESW could enhance the proliferation of SOP-BMSCs in a dose-dependent manner by EdU assay. Subsequently, the impact of r-ESW on the proliferation, apoptosis and multipotency of BMSCs was assessed. And the outcomes of flow cytometry, Alizarin red S (ARS), and tube formation test demonstrated that the optimal shockwave obviously boosted SOP-BMSCs osteogenesis and angiogenesis but exhibited no significant impact on cell apoptosis. Additionally, the signaling of Piezo1 and CaMKII/CREB was examined by Western blotting, qPCR and immunofluorescence. And the results showed that r-ESW promoted the expression of Piezo1, increased intracellular Ca2+ and activated the CaMKII/CREB signaling pathway. Then, the application of Piezo1 siRNA hindered the r-ESW-induced enhancement ability of osteogenesis coupling with angiogenesis of SOP-BMSCs. The use of the CaMKII/CREB signaling pathway inhibitor KN93 suppressed the Piezo1-induced increase in osteogenesis and angiogenesis in SOP-BMSCs. Finally, we also found that r-ESW might alleviate SOP in the senescence-accelerated mouse prone 6 (SAMP6) model by activating Piezo1. In conclusion, our research offers experimental evidence and an elucidated underlying molecular mechanism to support the use of r-ESW as a credible rehabilitative treatment for senile osteoporosis.

Bilirubin influences the predictive effect of body mass index on hospital mortality in critically ill patients.

Introduction: Body mass index (BMI) can predict mortality in critically ill patients. Moreover, mortality is related to increased bilirubin levels. Thus, herein, we aimed to investigate the effect of bilirubin levels on the usefulness of BMI in predicting mortality in critically ill patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC IV) database. Patients were divided into two groups according to their total bilirubin levels within 24 h. Cox proportional hazard regression models were applied to obtain adjusted hazard ratios and 95 % confidence intervals for the correlation between BMI categories and hospital mortality. The dose-response relationship was flexibly modeled using a restricted cubic spline (RCS) with three knots. Results: Of the 14376 patients included, 3.4 % were underweight, 29.3 % were of normal body weight, 32.2 % were overweight, and 35.1 % were obese. For patients with total bilirubin levels <2 mg/dL, hospital mortality was significantly lower in patients with obesity than in normal body weight patients (p < 0.05). However, the opposite results were observed for patients with total bilirubin levels ≥2 mg/dL. The Cox proportional hazard regression models suggested that the risk of death was lower in patients with overweightness and obesity than in normal body weight patients when the total bilirubin levels were <2 mg/dL, but not in the other case (total bilirubin levels ≥2 mg/dL). RCS analyses showed that, for patients with total bilirubin levels <2 mg/dL, the risk of death gradually decreased with increasing BMI. Conversely, for patients with total bilirubin levels ≥2 mg/dL, this risk did not decrease with increasing BMI until reaching obesity, after which it increased rapidly. Conclusion: BMI predicted the risk of death differently in critically ill patients with different bilirubin levels.

Advancements in Chemical and Biosensors for Point-of-Care Detection of Acrylamide.

Acrylamide (AA), an odorless and colorless organic small-molecule compound found generally in thermally processed foods, possesses potential carcinogenic, neurotoxic, reproductive, and developmental toxicity. Compared with conventional methods for AA detection, bio/chemical sensors have attracted much interest in recent years owing to their reliability, sensitivity, selectivity, convenience, and low cost. This paper provides a comprehensive review of bio/chemical sensors utilized for the detection of AA over the past decade. Specifically, the content is concluded and systematically organized from the perspective of the sensing mechanism, state of selectivity, linear range, detection limits, and robustness. Subsequently, an analysis of the strengths and limitations of diverse analytical technologies ensues, contributing to a thorough discussion about the potential developments in point-of-care (POC) for AA detection in thermally processed foods at the conclusion of this review.

Loss of Smooth Muscle Tenascin-X Inhibits Vascular Remodeling Through Increased TGF-ß Signaling.

BACKGROUND: Vascular smooth muscle cells (VSMCs) are highly plastic. Vessel injury induces a phenotypic transformation from differentiated to dedifferentiated VSMCs, which involves reduced expression of contractile proteins and increased production of extracellular matrix and inflammatory cytokines. This transition plays an important role in several cardiovascular diseases such as atherosclerosis, hypertension, and aortic aneurysm. TGF-ß (transforming growth factor-ß) is critical for VSMC differentiation and to counterbalance the effect of dedifferentiating factors. However, the mechanisms controlling TGF-ß activity and VSMC phenotypic regulation under in vivo conditions are poorly understood. The extracellular matrix protein TN-X (tenascin-X) has recently been shown to bind TGF-ß and to prevent it from activating its receptor. METHODS: We studied the role of TN-X in VSMCs in various murine disease models using tamoxifen-inducible SMC-specific knockout and adeno-associated virus-mediated knockdown. RESULTS: In hypertensive and high-fat diet-fed mice, after carotid artery ligation as well as in human aneurysmal aortae, expression of Tnxb, the gene encoding TN-X, was increased in VSMCs. Mice with smooth muscle cell-specific loss of TN-X (SMC-Tnxb-KO) showed increased TGF-ß signaling in VSMCs, as well as upregulated expression of VSMC differentiation marker genes during vascular remodeling compared with controls. SMC-specific TN-X deficiency decreased neointima formation after carotid artery ligation and reduced vessel wall thickening during Ang II (angiotensin II)-induced hypertension. SMC-Tnxb-KO mice lacking ApoE showed reduced atherosclerosis and Ang II-induced aneurysm formation under high-fat diet. Adeno-associated virus-mediated SMC-specific expression of short hairpin RNA against Tnxb showed similar beneficial effects. Treatment with an anti-TGF-ß antibody or additional SMC-specific loss of the TGF-ß receptor reverted the effects of SMC-specific TN-X deficiency. CONCLUSIONS: In summary, TN-X critically regulates VSMC plasticity during vascular injury by inhibiting TGF-ß signaling. Our data indicate that inhibition of vascular smooth muscle TN-X may represent a strategy to prevent and treat pathological vascular remodeling.

Biological functions and therapeutic potential of SRY related high mobility group box 5 in human cancer.

Cancer is a heavy human burden worldwide, with high morbidity and mortality. Identification of novel cancer diagnostic and prognostic biomarkers is important for developing cancer treatment strategies and reducing mortality. Transcription factors, including SRY associated high mobility group box (SOX) proteins, are thought to be involved in the regulation of specific biological processes. There is growing evidence that SOX transcription factors play an important role in cancer progression, including tumorigenesis, changes in the tumor microenvironment, and metastasis. SOX5 is a member of SOX Group D of Sox family. SOX5 is expressed in various tissues of human body and participates in various physiological and pathological processes and various cellular processes. However, the abnormal expression of SOX5 is associated with cancer of various systems, and the abnormal expression of SOX5 acts as a tumor promoter to promote cancer cell viability, proliferation, invasion, migration and EMT through multiple mechanisms. In addition, the expression pattern of SOX5 is closely related to cancer type, stage and adverse clinical outcome. Therefore, SOX5 is considered as a potential biomarker for cancer diagnosis and prognosis. In this review, the expression of SOX5 in various human cancers, the mechanism of action and potential clinical significance of SOX5 in tumor, and the therapeutic significance of Sox5 targeting in cancer were reviewed. In order to provide a new theoretical basis for cancer clinical molecular diagnosis, molecular targeted therapy and scientific research.

Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

The Efficacy and Safety of Anlotinib Plus Etoposide with Cisplatin/Carboplatin in the First-Line Treatment of Lung Cancer: A Phase II Clinical Study.

Background: The primary aim of this phase II clinical study was to assess the safety and efficacy of combining anlotinib, etoposide, and platinum-based drugs as a first-line treatment for ES-SCLC. Methods: Patients underwent the standard chemotherapeutic regimen, consisting of four courses of etoposide plus cisplatin/carboplatin. Additionally, each patient received a 2-week intervention with anlotinib (12 mg/day, once daily). Anlotinib was continued until disease progression, occurrence of unbearable adverse events (AEs), or withdrawal from the research. Progression-free survival (PFS) served as the primary prognostic measure. Secondary measures included the disease control rate (DCR), objective response rate (ORR), overall survival time (OS), and the incidence of AEs. Results: The DCR and ORR were 97.6% and 91.0%, respectively. Estimated PFS and OS were 5.0 months (95% CI: 1.0-10.8 months) and 13.0 months (95% CI: 8.4-18.6 months), respectively. No unexpected adverse effects were reported during the trial. The most common adverse reactions included anemia (42.22%), hypertension (53.33%), alopecia (40.00%), elevated transaminase (24.40%), and elevated alkaline phosphatase (24.44%). Sixteen cases (35.56%) were classified as AEs of grades 3-5. No deaths attributed to treatment-related causes occurred in any patient during the trial. Conclusion: Combination chemotherapy is currently the first-line therapy for extensive small-cell lung cancer (ES-SCLC). Combining anlotinib with conventional platinum-based chemotherapy demonstrated promising therapeutic outcomes and prognosis in the management of ES-SCLC.

Construction of a novel aminofluorene-based ratiometric near-infrared fluorescence probe for detecting carboxylesterase activity in living cells.

Herein, we constructed a novel aminofluorene-based fluorescence probe (FEN-CE) for the detection of carboxylesterase (CE) in living cells by a ratiometric near-infrared (NIR) fluorescence signal. FEN-CE with NIR emission (650 nm) could be hydrolyzed specifically by CE and transformed to FENH with the release of the self-immolative group, which exhibited a red-shifted emission peak of 680 nm. In addition, FEN-CE showed high selectivity for CE and was successfully used in the detection of CE activity in living cells through its ratiometric NIR fluorescence signals.

Low-Temperature and High-Efficiency Solid-Phase Amplification Based on Formamide.

The thermal stability of DNA immobilized on a solid surface is one of the factors that affects the efficiency of solid-phase amplification (SP-PCR). Although variable temperature amplification ensures high specificity of the reaction by precisely controlling temperature changes, excessively high temperatures during denaturation can negatively affect DNA stability. Formamide (FA) enables DNA denaturation at lower temperatures, showing potential for SP-PCR. Research on FA's impacts on DNA microarrays is still limited, necessitating further optimization in exploring the characteristics of FA in SP-PCR according to particular application needs. We immobilized DNA on a chip using a crosslinker and generated DNA microarrays through bridge amplification based on FA denaturation on our automated reaction device. We optimized the denaturation and hybridization parameters of FA, achieving a maximum cluster density of 2.83 × 104 colonies/mm2. Compared to high-temperature denaturation, FA denaturation required a lower template concentration and milder reaction conditions and produced higher cluster density, demonstrating that FA effectively improves hybridization rates on surfaces. Regarding the immobilized DNA stability, the FA group exhibited a 45% loss of DNA, resulting in a 15% higher DNA retention rate compared to the high-temperature group, indicating that FA can better maintain DNA stability. Our study suggests that using FA improves the immobilized DNA stability and amplification efficiency in SP-PCR.

Identification of disease-specific genes related to immune infiltration in nonalcoholic steatohepatitis using machine learning algorithms.

To identify disease signature genes associated with immune infiltration in nonalcoholic steatohepatitis (NASH), we downloaded 2 publicly available gene expression profiles, GSE164760 and GSE37031, from the gene expression omnibus database. These profiles represent human NASH and control samples and were used for differential genes (DEGs) expression screening. Two machine learning methods, the Least Absolute Shrinkage and Selection Operator regression model and Support Vector Machine Recursive Feature Elimination, were used to identify candidate disease signature genes. The CIBERSORT deconvolution algorithm was employed to analyze the infiltration of 22 immune cell types in NASH. Additionally, we constructed a NASH cell model using HepG2 cells treated with oleic acid and free fatty acids. The construction of the cell model was verified using oil red O staining, and Western blotting was used to detect the protein expression of the disease signature genes in both control and model groups. As a result, a total of 262 DEGs were identified. These DEGs were primarily associated with metal ion transmembrane transporter activity, sodium ion transmembrane transporter protein activity, calcium ion, and neuroactive ligand-receptor interactions. FOS, IGFBP2, dual-specificity phosphatase 1 (DUSP1), and IKZF3 were identified as disease signature genes of NASH by the least absolute shrinkage and selection operator and Support Vector Machine Recursive Feature Elimination algorithms for DEGs analysis. The receiver operating characteristic curves showed that FOS, IGFBP2, DUSP1, and IKZF3 had good diagnostic value (area under receiver operating characteristic curve > 0.8). These findings were validated in the GSE89632 dataset and through cellular assays. Immunocyte infiltration analysis revealed that NASH was associated with CD8 T cells, CD4 T cells, follicular helper T cells, resting NK cells, eosinophils, regulatory T cells, and γδ T cells. The FOS, IGFBP2, DUSP1, and IKZF3 genes were specifically associated with follicular helper T cells. Lipid droplet aggregation significantly increased in HepG2 cells treated with oleic acid and free fatty acids, indicating successful construction of the cell model. In this model, the expression of FOS, IGFBP2, and DUSP1 was significantly decreased, while that of IKZF3 was significantly elevated (P < .01, P < .001) compared with the control group. Therefore, FOS, IGFBP2, DUSP1, and IKZF3 can be considered as disease signature genes associated with immune infiltration in NASH.

A Microfluidic Chip for Single-Cell Capture Based on Stagnation Point Flow and Boundary Effects.

The capture of individual cells using microfluidic chips represents a widely adopted and efficient approach for investigating the biochemical microenvironment of singular cells. While conventional methods reliant on boundary effects pose challenges in precisely manipulating individual cells, single-cell capture grounded in the principle of stagnation point flow offers a solution to this limitation. Nevertheless, such capture mechanisms encounter inconsistency due to the instability of the flow field and stagnation point. In this study, a microfluidic device for the stable capture of single cells was designed, integrating the principle of fluid mechanics by amalgamating stagnation point flow and boundary effects. This innovative microfluidic chip transcended the limitations associated with single methodologies, leveraging the strengths of both stagnation point flow and boundary effects to achieve reliable single-cell capture. Notably, the incorporation of capture ports at the stagnation point not only harnessed boundary effects but also enhanced capture efficiency significantly, elevating it from 31.9% to 83.3%, thereby augmenting capture stability. Furthermore, computational simulations demonstrated the efficacy of the capture ports in entrapping particles of varying diameters, including 9 µm, 14 µm, and 18 µm. Experiment validation underscored the capability of this microfluidic system to capture single cells within the chip, maintaining stability even under flow rate perturbations spanning from 60 µL/min to 120 µL/min. Consequently, cells with dimensions between 8 µm and 12 µm can be reliably captured. The designed microfluidic system not only furnishes a straightforward and efficient experimental platform but also holds promise for facilitating deeper investigations into the intricate interplay between individual cells and their surrounding microenvironment.

Radiomic signatures associated with tumor immune heterogeneity predict survival in locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma (lrNPC) is limited due to their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in lrNPC. METHODS: This multicenter, retrospective study included 921 patients with lrNPC. A machine learning signature and nomogram based on pretreatment MRI features were developed for predicting overall survival (OS) in a training cohort and validated in two independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index (C-index) and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA sequencing (RNA-seq) analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving C-indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables significantly improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with significantly distinct OS rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-seq analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: An MRI-based radiomic signature predicted OS more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for lrNPC patients.

A Multiplex Recombinase-Aided qPCR Assay for Highly Sensitive and Rapid Detection of khe, blaKPC -2, and blaNDM -1 Genes in Klebsiella pneumoniae.

OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.

Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment.

BACKGROUND: The cognitive impairment in type 2 diabetes mellitus (T2DM) is a multifaceted and advancing state that requires further exploration to fully comprehend. Neuroinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease. AIM: To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment. METHODS: To identify differentially expressed genes (DEGs) between T2DM and controls, we used data from the Gene Expression Omnibus database GSE125387. To identify T2DM module genes, we used Weighted Gene Co-Expression Network Analysis. All the genes were subject to Gene Set Enrichment Analysis. Protein-protein interaction network construction and machine learning were utilized to identify three hub genes. Immune cell infiltration analysis was performed. The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis. Validation experiments including reverse transcription quantitative real-time PCR, Western blotting and immunohistochemistry were conducted both in vivo and in vitro. To identify potential drugs associated with hub genes, we used the Comparative Toxicogenomics Database (CTD). RESULTS: A total of 576 DEGs were identified using GSE125387. By taking the intersection of DEGs, T2DM module genes, and immune-related genes, a total of 59 genes associated with the immune system were identified. Afterward, machine learning was utilized to identify three hub genes (H2-T24, Rac3, and Tfrc). The hub genes were associated with a variety of immune cells. The three hub genes were validated in GSE152539. Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro, consistent with the bioinformatics analysis. Additionally, 11 potential drugs associated with RAC3 and TFRC were identified based on the CTD. CONCLUSION: Immune-related genes that differ in expression in the hippocampus are closely linked to microglia. We validated the expression of three hub genes both in vivo and in vitro, consistent with our bioinformatics results. We discovered 11 compounds associated with RAC3 and TFRC. These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.

Association Between Preoperative Sleep Disturbance and Postoperative Delirium in Elderly: A Retrospective Cohort Study.

Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.