Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Objective To investigate the correlation between platelet-to-albumin ratio(PAR)and occurrence of cerebral infarction after left atrial appendage closure(LAAC)in patients with non-valvular atrial fibrillation(NVAF).Methods A retrospective study was conducted on 259 NVAF patients undergoing LAAC in our department between 2019 and 2023.According to occurrence of cerebral infarction after LAAC or not,they were divided into a control group(241 cases)and a study group(18 cases).Their general data were collected,and Cox proportional hazards regression model was used to identify the risk factors for cerebral infarction.ROC curve was plotted to assess the predictive value of PAR for cerebral infarction in NVAF patients after LAAC,and the AUC value was calculated.Kaplan-Meier survival curve was drawn to analyze the incidence of cerebral infarction after LAAC in NVAF patients with different PAR values.Results The study group had significantly advanced age,higher SBP at admission,increased WBC,neutrophil,monocyte and platelet counts,longer thrombin time,elevated international normalized ratio(INR)and high-sensitivity C-reactive protein(hs-CRP)level,and higher PAR than the control group(P＜0.05,P＜0.01).Multivariate Cox regression analysis showed that PAR(HR=2.286,95％CI:1.182-4.420,P＜0.05)was an independent risk factor for cerebral infarction in NVAF patients after LAAC.ROC curve indicated that the AUC value of PAR in predicting cerebral infarction after LAAC in NVAF patients was 0.721(95％CI:0.586-0.856,P＜0.01),with an optimal cut-off value of 4.137,a sensitivity of 66.39％,and a specificity of 77.78％.Kaplan-Meier survival curve revealed that the higher the PAR value was,the higher the risk of cerebral infarction was(P＜0.01).Conclusion PAR is significantly correlated with cerebral infarction in NVAF patients after LAAC.The higher the PAR,the higher the risk of cerebral infarction,demonstrating its predictive value and being worthy of clinical promotion.

Objective:To investigate the influencing factors of major adverse cardiovascular events (MACE) in maintenance hemodialysis (MHD) patients, and to construct and verify the nomogram.Methods:The clinical data of 240 patients with MHD admitted to the First Affiliated Hospital of Hebei North University from July 2022 to October 2023 were retrospectively analyzed. According to whether the patients had MACE, they were divided into two groups, namely the occurrence group (with MACE, n=55) and the non-occurrence group (without MACE, n=185). After comparing the clinical data of the two groups, The independent risk factors of MHD patients with MACE were screened by binary logistic regression analysis, and the risk nomogram prediction model was constructed according to the risk factors, and the prediction efficiency of the model was analyzed by Bootstrap method. Results:There were significant differences in age, dialysis age, hyperlipidemia, hyperuricemia and hemodialysis flux between the two groups (all P<0.05). Binary logistic regression model analysis showed that dialysis age >12 months, combined with hyperlipidemia, combined with hyperuricemia, and low throughput hemodialysis were independent risk factors for MHD patients with MACE (all P<0.05). The neomorph risk prediction model was constructed based on independent risk factors. The area under the curve (AUC) of the prediction model was 0.842(95% CI: 0.789-0.896), the specificity was 69.1%, the sensitivity was 89.7%, the cutoff value was 13.128, and the Yoden index was 0.588, suggesting that the accuracy of the model was good. Conclusions:Dialysis age >12 months, combined with hyperlipidemia, combined with hyperuricemia and low throughput hemodialysis are independent risk factors for MACE in MHD patients. Intervention and control of risk factors can reduce the incidence of MACE.

Objective:To assess the predictive value of acute liver failure (ALF) for sepsis-free survival (SFS) in burn patients and to identify associated risk factors.Methods:A retrospective cohort study was conducted on burn patients meeting inclusion criteria from the 2014 Kunshan aluminum dust explosion disaster (August 2, 2014 - April 13, 2015). Eligible patients were stratified into ALF and non-ALF groups based on the development of ALF. Demographic characteristics, total burn surface area, organ dysfunction, time to sepsis onset, and clinical outcomes were collected and compared between groups. Kaplan-Meier survival analysis and multivariate Cox regression were performed to assess the impact of ALF on SFS. A nomogram model was constructed for individualized risk prediction.Results:Among 185 enrolled patients (ALF group:21, non-ALF group:164), ALF incidence was 11.35%. The ALF group demonstrated higher mortality (85.71% vs. 34.15%, P<0.001) and SFS failure rates (100.00% vs. 61.59%, P<0.001) compared to non-ALF patients. Multivariate Cox analysis identified ALF as an independent sepsis predictor ( HR=1.68, 95% CI: 1.00-2.80, P<0.05). Time-dependent ROC analysis showed AUCs of 0.626, 0.714, 0.703, and 0.706 for SFS prediction at 2, 4, 8, and 12 weeks respectively. The nomogram model demonstrated that ALF combined with other parameters effectively predicted sepsis risk within 2-12 weeks post-injury. ALF development showed significant associations with concurrent organ dysfunction including acute kidney injury, acute heart failure, and acute respiratory distress syndrome (all P<0.001). A higher proportion of ALF patients received hemodialysis ( P<0.001) and pre-hospital central venous catheterization ( P=0.017). Conclusions:ALF independently predicts SFS failure and correlates strongly with poor prognosis in burn patients. Early ALF recognition and targeted interventions may facilitate sepsis risk stratification and precision prevention strategies.

ObjectiveTo investigate the features of liver histopathological damage in patients with indeterminate phase of chronic HBV infection， as well as the timing for initiating antiviral therapy in such patients. MethodsA retrospective screening was performed for the patients with chronic HBV infection who were hospitalized in The Fifth Medical Center of Chinese PLA General Hospital and underwent liver biopsy from March 2018 to April 2022， among whom the patients who met the criteria for indeterminate phase defined in Chinese guidelines for chronic hepatitis B prevention and treatment （2022 edition） were enrolled， and their clinical data were collected. Liver histopathological stage was determined using the Scheuer scoring system， with stages 0 — 4 for inflammation grade （G） and stages 0 — 4 for fibrosis degree （S）， and the patients were divided into groups based on the presence of significant necroinflammation （≥G2） and significant liver fibrosis （≥S2）. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A Spearman’s rank correlation analysis was used to investigate the correlation between liver histopathology and clinical factors， and the Logistic regression model was used to identify the independent influencing factors for significant necroinflammation and liver fibrosis. ResultsA total of 271 patients with indeterminate phase of chronic HBV infection were enrolled， among whom 61 （22.5%） had significant necroinflammation （≥G2） and 124 （45.8%） had significant liver fibrosis （≥S2）. The Logistic regression analysis showed that alanine aminotransferase ≥30 U/L （for male patients） or ≥19 U/L （for female patients） （odds ratio ［OR］=2.69， 95% confidence interval ［CI］： 1.39 — 5.21， P=0.003）， HBV DNA ≥2 000 IU/mL （OR=2.75， 95%CI： 1.38 — 5.48， P=0.004）， and liver stiffness measurement （LSM） ≥6.0 kPa （OR=4.57， 95%CI： 2.17 — 9.62， P<0.001） were independent risk factors for significant inflammation. HBV DNA ≥2 000 IU/mL （OR=1.82， 95%CI： 1.01 — 3.32， P=0.049） and LSM ≥6.0 kPa （OR=2.06， 95%CI： 1.23 — 3.43， P=0.006） were independent influencing factors for significant liver fibrosis. ConclusionAmong the patients with indeterminate phase of chronic HBV infection， a substantial proportion of patients have significant liver histopathological damage. Antiviral therapy should be initiated in a timely manner for patients with high-risk factors.

The advancement of medical technology has led to significant progress in the research of standardized surgical procedures for colorectal cancer, resulting in enhanced treatment regimens from preoperative to postoperative stages. Standardized surgical procedures are crucial for improving patient survival rates, reducing recurrence rates, minimizing complications, and improving quality of life. This article summarizes the latest research results on the classification, surgical methods, and adjuvant therapy of colorectal cancer surgery; analyzes and explores standardized surgical treatment strategies; and aims to provide reference and guidance for the clinical management of colorectal cancer.

Cardiovascular disease is the leading cause of death worldwide,with atherosclerosis(AS)-its core pathological manifestation-representing a multifactorial-driven chronic inflammatory disorder.The pathogenesis of AS involves intricate pathological mechanisms including dyslipidemia,inflammatory cascades,and plaque vulnerability,whose complexity necessitates animal models capable of accurately recapitulating specific pathological features.Genetically engineered murine models have emerged as pivotal tools for deciphering AS mechanisms,owing to their genetic manipulability,phenotypic traceability,and molecular conservation with human pathophysiology.This review provides a systematic overview of current methodologies for establishing AS mouse models,with particular emphasis on evaluating the pathological fidelity of dietary induction approaches,genetic modification strategies[notably apolipoprotein E(ApoE)-/-and low density lipoproteins receptor(LDLr)-/-models],and physical injury paradigms.

Objective:To elucidate the causal association between gut microbiota and osteoporosis, we conducted a two-sample Mendelian randomization(MR)analysis to evaluate the causality between gut microbiota and osteoporosis.Methods:We assessed genome-wide association study (GWAS)summary statistics for gut microbiota and osteoporosis in older patients to perform the MR analysis.Independent single nucleotide polymorphisms closely associated with 211 gut bacterial taxa were identified as instrumental variables.The summary statistic data for osteoporosis were obtained from the latest release from the FinnGen consortium as the outcome of interest.Two-sample MR was performed to evaluate the causal effect of gut microbiota on osteoporosis, including the inverse-variance-weighted(IVW)method, weighted median method, MR-Egger, mode-based estimation, and MR-PRESSO.A series of sensitivity analyses were conducted to validate the robustness of the results.The robustness of the estimation was assessed through a series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plot to evaluate the causal association. Results:The population primarily consisted of individuals from Europe, with a total sample size of 7 300, including 1 762 males and 5 538 females, and average ages of 65.6 years for males and 67.8 years for females, respectively.The mean ages of the 5 538 patients were 65.6 years for males and 67.8 years for females, respectively.Through MR analysis in this study, 10 intestinal flora(comprising 1 class, 7 genera, and 2 orders)were identified as being associated with senile osteoporosis.Notably, the phylum Firmicutes( OR=1.324, P=0.019), Clostridium difficile( OR=1.274, P=0.038), fecal coliforms( OR=1.565, P=0.009), Verrucomicrobium( OR=1.231, P=0.033), and Selenomonas( OR=1.324, P=0.019)may serve as risk factors for senile osteoporosis.Conversely, Coprococcus( OR=0.620, P=0.024), Haemophilus( OR=0.815, P=0.016), Prevotella( OR=0.813, P=0.027), Sellimonas( OR=0.858, P=0.034), and RF9( OR=0.821, P=0.021)may function as protective factors against senile osteoporosis. Conclusions:This study suggests a causal relationship between the Firmicutes phylum and its nine subgroups and senile osteoporosis, thereby providing new insights into the mechanisms by which gut microbiota mediate senile osteoporosis and confirming the significant role of gut microbiota in this condition.

Objective To explore the correlation between systemic inflammatory response index(SIRI)and the prognosis of elderly heart failure(HF)patients.Methods A retrospective study was conducted on 300 elderly HF patients with complete medical records hospitalized in our de-partment from January to December 2022.During the follow-up period for 1 year in different ways,46 of them were lost,and 254 were finally included.Baseline data,complete blood count at admission,and results of auxiliary examinations,and medicine adherence after discharge were col-lected and recorded.According to the occurrence of major adverse cardiovascular events(MACE),the subjected patients were divided into a MACE group(96 cases)and a non-MACE group(158 cases).The baseline data and relevant examination indicators were compared between the two groups,and the relevant factors for the occurrence were analyzed by using logistic regression.ROC curve analysis was employed to assess the predictive value of SIRI for MACE occurrence.Results The MACE group had significantly advanced age,larger proportion of diabetes mellitus,higher neutrophil and platelet counts,and elevated D-dimer level,but lower standardized medication rate when compared with the non-MACE group(P＜0.05,P＜0.01).The SIRI level was obviously higher in the MACE group than the non-MACE group[1.70(1.13,2.33)vs 1.29(0.85,2.06),P=0.002].Multivariate logistic regression analysis showed that atrial fibrillation,standardized medi-cation,mononuclear cells,and SIRI were independent risk factors for the occurrence of MACE in elderly HF patients(P＜0.05,P＜0.01).ROC curve analysis indicated that the AUC value of SIRI in predicting the occurrence of MACE was 0.614(95％CI:0.544-0.683),with a sensitivity of 0.813 and a specificity of 0.437.Conclusion SIRI is significantly correlated with the occurrence of MACE in elderly HF patients,and has a certain predictive value for their prognosis.

The specific mechanisms of interferon regulatory factor 8(IRF8)in porcine intestinal in-nate immunity and resistance to enteric virus infection remain to be elucidated.To investigate the immunoregulatory role of IRF8,establishing an IRF8 gene knockout porcine intestinal epithelial cell(IPEC-J2)monoclonal cell line is of significant importance.This study initially aimed to obtain recombinant adeno-associated virus rAAV-sgIRF8-eGFP capable of knocking out the IRF8 gene through co-transfection of HEK-293T cells with three plasmids.Subsequently,IPEC-J2 cells were infected with the virus,and those expressing eGFP were selected by flow cytometry and cultured to form monoclonal cell lines.These cell lines were then identified by Sanger sequencing and West-ern blot techniques.Lastly,qPCR analysis was used to measure the expression levels of interferon factors IFN-α,IFN-β,IFN-γ and IFN-λ,providing preliminary insights into the impact of IRF8 gene knockout on IPEC-J2 cell immunity.The results demonstrated successful generation of rAAV-sgIRF8-eGFP,which successfully infected IPEC-J2 cells leading to eGFP fluorescence.Flow cytometry followed by cell culture led to the establishment of two monoclonal cell lines,IRF8-KO1 and IRF8-KO3.Sanger sequencing revealed a five-base deletion in IRF8-KO1 and a seven-base dele-tion in IRF8-KO3.Western blot confirmed the absence of IRF8 protein expression in IRF8-KO1,making it an ideal candidate monoclonal cell line.qPCR analysis of interferon factors indicated sig-nificant decrease in IFN-γ(P＜0.05)and IFN-λ(P＜0.01)transcription level in IRF8-knockout cells,while the transcription levels of IFN-α and IFN-β remained relatively unchanged.This study successfully established an IRF8 gene knockout IPEC-J2 monoclonal cell line,providing a founda-tion for further research on IRF8-related porcine intestinal immune regulation and mechanisms of intestinal virus infection.