Intrauterine fetal death due to rupture of umbilical vessels: a rare case of furcate cord insertion.

Furcate cord insertion refers to the separation of umbilical vessels before reaching the placenta, where the branching vessels normally attach at the edge of the placental parenchyma or near the placental membranes. This is an extremely rare abnormal umbilical cord insertion. This paper reported a case of a furcate cord insertion, where the rupture of exposed umbilical vessels led to intrauterine fetal death at full term. Through literature review, we analyzed the prenatal ultrasound characteristics and pregnancy outcomes of furcate cord insertions, with the aim to improve detection rates and reduce the risk of adverse pregnancy outcomes.

Retraction note: Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria.

[This retracts the article on p. 2173 in vol. 12, PMID: 38808336.].

Research progress on knowledge-attitude-practice of VTE prevention in hospitalized patients: A review.

This study analyzes and summarizes the assessment tools, current situation, and influencing factors of venous thromboembolism (VTE) prevention knowledge, attitudes, and practices (KAP) among patients. This study aimed to provide a reference basis for developing targeted health education plans and intervention strategies for patients to improve their knowledge and beliefs concerning VTE prevention. This study aimed to increase the implementation rate of VTE prevention measures and ultimately reduce the incidence of VTE.The current studies found that the factors influencing knowledge, attitude, and practice of VTE prevention in hospitalized patients include demographic factors (age, sex, education level, occupation), disease-related factors (treatment stage, injury site, and wards), and other factors (receiving VTE-related knowledge education and having medical workers at home).

Portal Venous and Hepatic Arterial Coefficients Predict Post-Hepatectomy Overall and Recurrence-Free Survival in Patients with Hepatocellular Carcinoma: A Retrospective Study.

Background: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy. Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models. Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534-2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290-1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149-2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380-2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005-2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236-2.263), higher BCLC stage (HR 1.516, 95% CI 1.300-1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198-2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060-1.997). Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients.

Unraveling anti-aging mystery of green tea in C. elegans: Chemical truth and multiple mechanisms.

Tea drinking impacts aging and aging-related diseases. However, knowledge of anti-aging molecules other than the major catechins in complex tea extracts remains limited. Here we used Caenorhabditis elegans to analyze the longevity effects of tea extracts and constituents comprehensively. We found that the hot water extract of green tea prolonged lifespan and heathspan. Further, the MeOH fraction prolonged lifespan significantly longer than other fractions. Correlation analysis between mass spectroscopic data and anti-aging activity suggests that ester-type catechins (ETCs) are the major anti-aging components, including 4 common ETCs, 6 phenylpropanoid-substituted ester-type catechins (PSECs), 5 cinnamoylated catechins (CCs), 7 ester-type flavoalkaloids (ETFs), and 4 cinnamoylated flavoalkaloids (CFs). CFs (200 µM) are the strongest anti-aging ETCs (with the longest 73% lifespan extension). Green tea hot water extracts and ETCs improved healthspan by enhancing stress resistance and reducing ROS accumulation. The mechanistic study suggests that they work by multiple pathways. Moreover, ETCs modulated gut microbial homeostasis, increased the content of short-chain fatty acids, and reduced fat content. Altogether, our study provides new evidence for the anti-aging benefits of green tea and insights into a deep understanding of the chemical truth and multi-target mechanism.

Radiomics in esophagogastric junction cancer: A scoping review of current status and advances.

PURPOSE: This scoping review aimed to understand the advances in radiomics in esophagogastric junction (EGJ) cancer and assess the current status of radiomics in EGJ cancer. METHODS: We conducted systematic searches of PubMed, Embase, and Web of Science databases from January 18, 2012, to January 15, 2023, to identify radiomics articles related to EGJ cancer. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies using the Radiomics Quality Score (RQS) and the METhodological RadiomICs Score (METRICS) tool, respectively. RESULTS: A total of 120 articles were retrieved from the three databases, and after screening, only six papers met the inclusion criteria. These studies investigated the role of radiomics in differentiating adenocarcinoma from squamous carcinoma, diagnosing T-stage, evaluating HER2 overexpression, predicting response to neoadjuvant therapy, and prognosis in EGJ cancer. The median score percentage of RQS was 34.7% (range from 22.2% to 38.9%). The median score percentage of METRICS was 71.2% (range from 58.2% to 84.9%). CONCLUSION: Although there is a considerable difference between the RQS and METRICS scores of the included literature, we believe that the research value of radiomics in EGJ cancer has been revealed. In the future, while actively exploring more diagnostic, prognostic, and biological correlation studies in EGJ cancer, greater emphasis should be placed on the standardization and clinical application of radiomics.

Effect of alveolar ridge preservation at periodontally compromised molar extraction sockets: A retrospective cohort study.

BACKGROUND: To date, the clinical evidence regarding the effectiveness of alveolar ridge preservation (ARP) in restricting alveolar bone height and width change after extraction at periodontally compromised molar extraction sockets still remains controversial. This retrospective cohort study aims to evaluate the effect of ARP in molars extracted for periodontal reasons. METHODS: Retrospective data were collected from patient electronic records from January 2019 to December 2023. Patients with Stage III/IV periodontitis who underwent extraction of molars for periodontal reasons were screened for eligibility. The outcomes included the horizontal and vertical dimensions of alveolar bone. The need for additional augmentation procedure during implantation was also evaluated. A linear regression model was used to adjust for known confounders. RESULTS: A total of 80 sockets were included in this study, of which 27 sockets received ARP therapy after extraction while 53 sockets experienced natural healing (NH). ARP resulted in significantly less bone height change in the periodontally compromised molar sites compared to the NH group (p < 0.001). In sockets displaying a height disparity of >2 mm between the buccal and palatal/lingual walls, the ARP group exhibited advantageous outcomes in terms of ridge width change, surpassing the NH group (p = 0.004). Moreover, the percentage for additional augmentation was significantly reduced in the ARP compared to the NH group (p = 0.006). Age, sex, smoking, jaw, location, and buccal wall thickness did not show any significant effect on bone height change. CONCLUSION: ARP had benefits on limiting ridge resorption subsequent to molar extraction for periodontal reasons.

Analysis of the current status of "pseudo" unplanned endotracheal extubation in ICU patients in China's tertiary hospitals.

To analyze the current status of "pseudo" unplanned endotracheal extubation in ICU patients in China's tertiary hospitals and to provide a reference for improving the quality of medical care. Through the National Nursing Quality Data Platform, unplanned endotracheal extubation data reported by ICUs in China's tertiary hospitals from 2019 to 2022 were analyzed. The situation of reported hospitals, causes, and the current status of "pseudo" unplanned endotracheal extubation in ICU patients was analyzed. The indicator of unplanned endotracheal extubation in ICUs of China's tertiary hospitals is mainly from first-class tertiary hospitals (74.9%), most of which are self-extractions by patients (74.6%). The proportion of "pseudo" unplanned endotracheal extubation is 45.1%. "Pseudo" unplanned endotracheal extubation is common in the ICUs of China's tertiary hospitals. As such, management blind spots deserve attention from managers and clinical staff.

An insight into trichomes-deficiency and trichomes-rich black teas by comparative metabolomics: The impact of oxidized trichomes on metabolic profiles and infusion color.

Tea trichomes were regarded as an essential evaluation index for reflecting tea flavor quality in terms of aroma and influence on infusion color. This study reveals the impact of golden oxidized trichomes on the color, volatile and non-volatile metabolites of black teas through comparative metabolomics combined quantitative analysis on hongbiluo (trichomes-deficiency black teas), hongjinluo (trichomes-rich black teas), and trichomes (from hongjinluo). Forty-six volatile components were detected using headspace solid-phase microextraction gas chromatography-mass spectrometry, while the results suggested that the contribution of trichomes to black teas is limited. A total of 60 marker non-volatile compounds were identified, including catechins, catechin oxidation products, flavonoid glycosides, organic acids, hydrolysable tannins and amino acids. Notably, p-coumaroyl-kaempferol glucosides, and catechin dimers demonstrated high levels in independent trichomes and showed a positive correlation with the brightness and yellow hue of black tea infusions, specifically kaempferol 3-O-di-(p-coumaroyl)-hexoside. Furthermore, results from fractional extraction analysis of separated trichomes provided that N-ethyl-2-pyrrolidinone-substituted epicatechin gallates, acylated kaempferol glycosides, and chromogenic catechins dimers, such as theaflavins, were primary color contributors in oxidized trichomes. Especially, we found that epicatechin gallate (ECG) and its derivates, 3'-O-methyl-ECG and N-ethyl-2-pyrrolidinone-substituted ECG, highly accumulated in trichomes, which may be associated with the varieties of hongbiluo and hongjinluo black teas. Eventually, addition tests were applied to verify the color contribution of trichome mixtures. Our findings employed comprehensive information revealing that golden oxidized trichomes contributed significantly to the brightness and yellow hue of black tea infusion, but their contribution to the aroma and metabolic profile is limited. These findings may contribute to the effective modulation of the infusion color during black tea production by regulating the proportion of tea trichomes or screening trichomes-rich or deficiency varieties.

Effects of baculovirus infection on intestinal microflora of BmNPV resistant and susceptible strain silkworm.

Bombyx mori L. (Lepidoptera: Bombycidae) nucleopolyhedrovirus (BmNPV) is a serious pathogen causing huge economic losses to sericulture. There is growing evidence that the gut microbiota of silkworms plays a critical role in shaping host responses and interactions with viral infection. However, little is known about the differences in the composition and diversity of intestinal microflora, especially with respect to silkworm strain differences and BmNPV infection-induced changes. Here, we aim to explore the differences between BmNPV-resistant strain A35 and susceptible strain P50 silkworm and the impact of BmNPV infection on intestinal microflora in different strains. The 16S rDNA sequencing analysis revealed that the fecal microbial populations were distinct between A35 and P50 and were significantly changed post BmNPV infection in both strains. Further analysis showed that the BmNPV-resistant strain silkworm possessed higher bacterial diversity than the susceptible strain, and BmNPV infection reduced the diversity of intestinal flora assessed by feces in both silkworm strains. In response to BmNPV infection, the abundance of Muribaculaceae increased in P50 and decreased in A35, while the abundance of Enterobacteriaceae decreased in P50 and increased in A35. These results indicated that BmNPV infection had various effects on the abundance of fecal microflora in different silkworm strains. Our findings not only broadened the understanding of host-pathogen interactions but also provided theoretical help for the breeding of resistant strains and healthy rearing of silkworms based on symbiotic bacteria.

Bone-metastatic lung adenocarcinoma cells bearing CD74-ROS1 fusion interact with macrophages to promote their dissemination.

Approximately 40% of patients with lung adenocarcinoma (LUAD) often develop bone metastases during the course of their disease. However, scarcely any in vivo model of LUAD bone metastasis has been established, leading to a poor understanding of the mechanisms underlying LUAD bone metastasis. Here, we established a multiorgan metastasis model via the left ventricular injection of luciferase-labeled LUAD cells into nude mice and then screened out lung metastasis (LuM) and bone metastasis (BoM) cell subpopulations. BoM cells exhibited greater stemness and epithelial-mesenchymal transition (EMT) plasticity than LuM cells and initially colonized the bone and subsequently disseminated to distant organs after being reinjected into mice. Moreover, a CD74-ROS1 fusion mutation (C6; R34) was detected in BoM cells but not in LuM cells. Mechanistically, BoM cells bearing the CD74-ROS1 fusion highly secrete the C-C motif chemokine ligand 5 (CCL5) protein by activating STAT3 signaling, recruiting macrophages in tumor microenvironment and strongly inducing M2 polarization of macrophages. BoM cell-activated macrophages produce a high level of TGF-ß1, thereby facilitating EMT and invasion of LUAD cells via TGF-ß/SMAD2/3 signaling. Targeting the CD74-ROS1/CCL5 axis with Crizotinib (a ROS1 inhibitor) and Maraviroc (a CCL5 receptor inhibitor) in vivo strongly impeded bone metastasis and secondary metastasis of BoM cells. Our findings reveal the critical role of the CD74-ROS1/STAT3/CCL5 axis in the interaction between LUAD bone metastasis cells and macrophages for controlling LUAD cell dissemination, highlighting the significance of the bone microenvironment in LUAD bone metastasis and multiorgan secondary metastasis, and suggesting that targeting CD74-ROS1 and CCL5 is a promising therapeutic strategy for LUAD bone metastasis.

A combination technique of strip free gingival grafts and xenogeneic collagen matrix in augmenting keratinized mucosa around dental implants: a single-arm clinical trial.

BACKGROUND: The aim of this study was to assess the outcomes of the combination technique of strip free gingival grafts (SFGG) and xenogeneic collagen matrix (XCM) in augmenting the width of keratinized mucosa (KMW) around dental implants, and compare its efficacy with the historical control group (FGG). METHODS: Thirteen patients with at least one site with KMW ≤ 2 mm after implant surgery were included and received SFGG in combination with XCM. Another thirteen patients with the same inclusion and exclusion criteria from the previous trial received FGG alone. The same outcomes as the previous trial were evaluated. KMW, thickness of keratinized mucosa (KMT), gingival index (GI) and probing depth (PD) were measured at baseline, 2 and 6 months. Postoperative pain, patient satisfaction and aesthetic outcomes were also assessed. RESULTS: At 6 months after surgery, the combination technique could attain 3.3 ± 1.6 mm of KMW. No significant change could be detected in GI or PD at 6 months compared to those at 2 months (p > 0.05). The postoperative pain and patient satisfaction in VAS were 2.6 ± 1.2 and 9.5 ± 1.2. The total score of aesthetic outcomes was 3.8 ± 1.2. In the historical FGG group, 4.6 ± 1.6 mm of KMW was reported at 6 months, and the total score of aesthetic outcomes was higher than the combination technique (4.8 ± 0.7 vs. 3.8 ± 1.2, p < 0.05). CONCLUSIONS: The combination technique of SFGG and XCM could increase KMW and maintain peri-implant health. However, this combination technique was associated with inferior augmentation and aesthetic outcomes compared with FGG alone. TRIAL REGISTRATION: This clinical trial was registered in the Chinese Clinical Trial Registry with registration number ChiCTR2200057670 on 15/03/2022.

Metabolic profiling of peri-implant crevicular fluid in peri-implantitis.

OBJECTS: This study aims to explore the etiology of peri-implantitis by comparing the metabolic profiles in peri-implant crevicular fluid (PICF) from patients with healthy implants (PH) and those with peri-implantitis (PI). MATERIALS AND METHODS: Fifty-six patients were enrolled in this cross-sectional study. PICF samples were collected and analyzed using both non-targeted and targeted metabolomics approaches. The relationship between metabolites and clinical indices including probing depth (PD), bleeding on probing (BOP), and marginal bone loss (MBL) was examined. Additionally, submucosal microbiota was collected and analyzed using 16S rRNA gene sequencing to elucidate the association between the metabolites and microbial communities. RESULTS: Significant differences in metabolic profiles were observed between the PH and PI groups, with 179 distinct metabolites identified. In the PI group, specific amino acids and fatty acids were significantly elevated compared to the PH group. Organic acids including succinic acid, fructose-6-phosphate, and glucose-6-phosphate were markedly higher in the PI group, showing positive correlations with mean PD, BOP, and MBL. Metabolites that increased in the PI group positively correlated with the presence of Porphyromonas and Treponema and negatively with Streptococcus and Haemophilus. CONCLUSIONS: This study establishes a clear association between metabolic compositions and peri-implant condition, highlighting enhanced metabolite activity in peri-implantitis. These findings open avenues for further research into metabolic mechanisms of peri-implantitis and their potential therapeutic implications.

P4HA2 activates mTOR via hydroxylation and targeting P4HA2-mTOR inhibits lung adenocarcinoma cell growth.

Mammalian target of rapamycin (mTOR) kinase functions as a central regulator of cell growth and metabolism, and its complexes mTORC1 and mTORC2 phosphorylate distinct substrates. Dysregulation of mTOR signaling is commonly implicated in human diseases, including cancer. Despite three decades of active research in mTOR, much remains to be determined. Here, we demonstrate that prolyl 4-hydroxylase alpha-2 (P4HA2) binds directly to mTOR and hydroxylates one highly conserved proline 2341 (P2341) within a kinase domain of mTOR, thereby activating mTOR kinase and downstream effector proteins (e.g. S6K and AKT). Moreover, the hydroxylation of P2341 strengthens mTOR stability and allows mTOR to accurately recognize its substrates such as S6K and AKT. The growth of lung adenocarcinoma cells overexpressing mTORP2341A is significantly reduced when compared with that of cells overexpressing mTORWT. Interestingly, in vivo cell growth assays show that targeting P4HA2-mTOR significantly suppresses lung adenocarcinoma cell growth. In summary, our study reveals an undiscovered hydroxylation-regulatory mechanism by which P4HA2 directly activates mTOR kinase, providing insights for therapeutically targeting mTOR kinase-driven cancers.

Dual-energy CT Portal Venography: Clinical Application Values and Future Opportunities.

Standard multidetector computed tomography (MDCT) uses a single X-ray tube to emit a mixed energy X-ray beam, which is received by a single detector. The difference is that dual-energy CT (DECT), a new equipment in recent years, employs a single X-ray tube or two X-ray tubes to emit two single-energy X-ray beams, which are received by a single or two detectors. The application of dual-energy technology to portal venography has become one of the research hotspots. This paper will elaborate on the clinical application values of DECT portal venography in improving portal vein image quality, distinguishing the nature of portal vein thrombus, reducing contrast agent dose and radiation dose, and will discuss the possibility of its movement from research to routine practice and future development opportunities.

The Association of Serum Complement C1q with Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Coronary artery disease (CAD) is one of the leading causes of death in middle-aged and elderly people, and its incidence has been increasing in recent years. An in-depth understanding of the pathogenesis of CAD is important to ensure the health of CAD patients. Objective: To analyze the association of serum complement C1q with CAD," you could say something like "The objective of this meta-analysis is to investigate the relationship between serum complement C1q levels and the presence of CAD, aiming to provide insights for clinical diagnosis and treatment. Methods: Relevant studies on C1q and CAD were searched in PubMed, Web of Science and other literature databases. Two research team members independently cross-screened the literature according to the inclusion-exclusion criteria and assessed the literature quality. RevMan5.3 software was used for statistical analysis. Results: Three references were finally included, all of which had a Newcastle-Ottawa Scale (NOS) score ≥6, indicating high quality. A total of 2065 subjects were studied, including 1249 in the experimental group (CAD patients) and 816 in the control group (healthy population). Through the meta-analysis, it was found that the experimental group (CAD patients) had higher serum C1q than the control group (healthy controls) (P < .05). According to subgroup analysis, age, sex, sample size, diabetes mellitus (with/without), and serum complement C1q detection methods were not factors affecting the heterogeneity of the literature, and more data are needed for verification. Validation analysis with the fixed-effect model also showed higher C1q expression in the experimental group (P < .05). The graph of the funnel plot was basically symmetrical, suggesting low publication bias. Conclusions: Serum complement C1q is elevated in CAD patients, but its mechanism of action may have a dual effect, but further research is needed to understand its precise role and clinical implications.

Revealing the variances in color formation and bioactivities of seven catechin monomers throughout the enzymatic reaction by colorimetric and mass spectrometry.

The capacity differences of seven catechin monomers to produce colors after treating with catechin-free extract were investigated. After 240-min reaction, only (-)-epicatechin (EC) and (+)-catechin (C) presented obvious luminous red color with L* values of 63.32-71.73, a* values of 37.13-46.44, and b* values of 65.64-69.99. Meanwhile, the decrease rate of EC and C was 43.52 %-50.35 %, which were significantly lower than those of other catechin monomers (85.91 %-100 %). The oxidized products of catechin monomers were analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry coupled with diode array detector, wherein dehydro-dimers and -trimers (oxidative coupling products of catechins' A-B ring) were found to be the major chromogenic compounds of EC and C. Additionally, the antioxidant capacity of catechin monomers only decreased after 30-min reaction, while along with further enzymatic reaction, catechin monomers presented comparable oxyradical scavenging ability (e.g., the DPPH inhibitory rates of catechin monomers were in the range of 24.42 %-50.77 %) to vitamin C (positive control, DPPH inhibitory rate was 27.66 %). Meanwhile, the inhibitory effects of most catechin monomers on α-glucosidase were enhanced in different degrees. These results provided basis for the development of enzymatically-oxidized catechin monomers as functional food color additives.

Deficiency of the HGF/Met pathway leads to thyroid dysgenesis by impeding late thyroid expansion.

The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.

Reprogramming fibroblast into human iBlastoids.

The study of early human embryogenesis has relied on the use of blastocysts donated to research or simple stem cell culture systems such as pluripotent and trophoblast stem cells, which have been seminal in shedding light on many key developmental processes. However, simple culture systems lack the necessary complexity to adequately model the spatiotemporal, cellular and molecular dynamics occurring during the early phases of embryonic development. As such, an in vitro model of the human blastocyst is advantageous in many aspects to decipher human embryogenesis. Here we describe a step-by-step protocol for the generation of induced blastoids (iBlastoids), an in vitro integrated model of the human blastocyst derived via somatic reprogramming. This protocol details the workflow for reprogramming of human dermal fibroblasts and subsequent generation of iBlastoids using the reprogramming intermediates, which together takes ~27 days (21 days for reprogramming and 6 days for iBlastoid generation). We also discuss several characterization/functional assays that can be used on the iBlastoids. We believe that a person trained in cell culture with ~1 year of experience with human somatic cell and reprogramming/cell differentiation assays would be able to perform this protocol. In short, the iBlastoids present an alternative tool as a model to the blastocyst to facilitate the scientific community in the exploration of early human development.

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. METHODS: C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. RESULTS: CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. CONCLUSIONS: Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.