ObjectiveTo investigate the possible mechanism of Shenfuhuang Formula （参附黄配方） in prevention and treatment of epsis-associated encephalopathy from the perspective of brain genomics. MethodsC57BL/6 mice were randomly divided into sham surgery group， sepsis group， and Shenfuhuang group， with 20 mice in each group. The sepsis group and Shenfuhuang group were induced to develop sepsis by cecal ligation and puncture （CLP） procedure. At 4 hours after modelling， Shenfuhuang group were gavaged with 2.5 g/（kg·d） of Shenfuhuang Formula， 0.5 ml each time， at 12 hours intervals， for a total of 4 times after modelling. Sepsis group and sham surgery group were given 0.5 ml of purified water orally. At 48 hours after modeling， the transcriptome sequencing was used to explore the differential gene expression in the effects of Shenfuhuang Formula on the brain regions of septic mice， and real-time PCR and ELISA were later used to further validate the differential gene and proteins expression. ResultsA total of 4605 genes were differentially expressed in Shenfuhuang group compared with sepsis group， of which 2353 genes were up-regulated and 2252 genes were down-regulated. According to the results of previous publications， six key genes were screened， including serine/threonine-protein kinase （Nek1）， myelin-associated glycoprotein （Mag）， endothelial cell-specific tyrosine kinase receptor （Tek）， a disintegrin and metalloproteinase with thrombospondin motifs 20 （Adamts20）， lymphocyte antigen 86 （Ly86）， and E3 ubiquitin-protein ligase （Traip）. Further genetic and protein validation revealed that， compared to the sham surgery group， the mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip in the brain tissue of septic mice significantly reduced （P＜0.05）. In comparison to the sepsis group， Shenfuhuang group showed significantly increased mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip （P＜0.05）. ConclusionThe potential therapeutic targets of Shenfuhuang Formula for treating sepsis-associated encephalopathy may be related to the Nek1， Mag， Tek， Adamts20， Ly86， and Traip genes and their encoded proteins.

Alzheimer's disease (AD) is characterized by cognitive and functional deterioration, with pathological features such as amyloid-beta (Aβ) aggregates in the extracellular spaces of parenchymal neurons and intracellular neurofibrillary tangles formed by the hyperphosphorylation of tau protein. Despite a thorough investigation, current treatments targeting the reduction of Aβ production, promotion of its clearance, and inhibition of tau protein phosphorylation and aggregation have not met clinical expectations, posing a substantial obstacle in the development of drugs for AD. Recently, artificial intelligence (AI), computational biology (CB), and systems biology (SB) have emerged as promising methodologies in AD research. Their capacity to analyze extensive and varied datasets facilitates the identification of intricate patterns, thereby enriching our comprehension of AD pathology. This paper provides a comprehensive examination of the utilization of AI, CB, and SB in the diagnosis of AD, including the use of imaging omics for early detection, drug discovery methods such as lecanemab, and complementary therapies like phototherapy. This review offers novel perspectives and potential avenues for further research in the realm of translational AD studies.

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

Abstract Aspirin (ASA) is widely used for primary and secondary prevention of cardiovascular disease (CVD), but its strategy of application is highly controversial. Meanwhile, in terms of ASA prevention strategies for CVD, countries around the world are different. The United States is becoming increasingly cautious, while the European Union tends to focus on the benefits of ASA clinical use. China is concerned about the effectiveness of ASA in preventing CVD in the elderly. This article reviews relevant literature published domestically and internationally from 2005 to 2024 for the application of ASA in CVD prevention, ASA prevention strategies for CVD in main countries and the application of ASA in special groups such as chronic disease patients, which provides a basis for improving ASA prevention strategies for CVD and standardizing clinical application of ASA in China.

Visual hallucination(VH)is a common symptom of schizophrenia,the underlying mechanism has not been fully elucidated.It has been found that the dysfunction of dopamine(DA)system,the overactivation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate(AMPA)receptor in glutamate system and the dysfunction of γ-aminobutyric acid(GABA)ergic neurons can induce VH in patients with schizophrenia.In addition,abnormalities in brain structural and functional networks and visual networks are also closely related to the occurrence of VH.The purpose of this paper is to review the neurochemistry and nerve injury mechanism of VH in schizophrenic patients to deeply understand the characteristics of VH,and make more accurate judgment in the early diagnosis,condition evaluation and treatment plan of schizophrenic patients.

Objective:To evaluate the safety and feasibility of transumbilical single-port transabdominal preperitoneal hernioplasty plus cholecystectomy (SILS-TAPP+LC).Methods:The clinical data of 52 adult patients who underwent [SILS-(TAPP+LC)] from Mar, 2019 to Oct, 2021 at the Affiliated Hospital of Nantong University were retrospectively analyzed.The perioperative indicators, postoperative complications and follow-up data were analyzed.Results:All operations were successfully completed without conversion to open or multi-port laparoscopic surgery.The duration of surgery was (49.2 ± 7.5) min. Three patients experienced gallbladder rupture, and there was no bladder or intestinal injury during the surgery.During the 20-24 months of postoperative follow-up period,4 patient developed seroma in the postoperative period, 4 patients complained foreign body sense in the inguinal region, 3 patients reported chronic pain, but no other complications, such as biliary fistula, recurrence, mesh infection, or trocar hernia, were observed.Conclusion:SILS-(TAPP+LC) was a safe and feasible approach associated with little postoperative pain and rapid recovery.

The biofilms formed by pathogenic microorganisms seriously threaten human health and significantly enhance drug resistance, which urgently call for developing drugs specifically targeting on biofilms. Chitooligosaccharides extracted from shrimp and crab shells are natural alkaline oligosaccharides with excellent antibacterial effects. Nevertheless, their inhibition efficacy on biofilms still needs to be improved. Spirulina (SP) is a microalga with negatively charged surface, and its spiral structure facilitates colonization in the depth of the biofilm. Therefore, the complex of Spirulina and chitooligosaccharides may play a synergistic role in killing pathogens in the depth of biofilm. This research first screened chitooligosaccharides with significant bactericidal effects. Subsequently, Spirulina@Chitooligosaccharides (SP@COS complex was prepared by combining chitooligosaccharides with Spirulina through electrostatic adsorption. The binding of the complex was characterized by zeta potential, z-average size, and fluorescence labeling. Ultraviolet-visible spectroscopy (UV-Vis) showed the encapsulation efficiency and the drug loading efficiency reached up to 90% and 16%, respectively. The prepared SP@COS2 exhibited a profound synergistic inhibition effect on bacterial and fungal biofilms, which was mainly achieved by destroying the cell structure of the biofilm. These results demonstrate the potential of Spirulina-chitooligosaccharides complex as a biofilm inhibitor and provide a new idea for addressing the harm of pathogenic microorganisms.
Humans ; Spirulina ; Anti-Bacterial Agents/chemistry* ; Chitosan/pharmacology* ; Biofilms ; Chitin/pharmacology*

OBJECTIVES: This study aimed to observe the clinical and immune response characteristics of vaccinated persons infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Yangzhou, China. METHODS: We extracted the medical data of 129 patients with delta-variant infection who were admitted to Northern Jiangsu People's Hospital (Yangzhou, China) between August and September, 2021. The patients were grouped according to the number of vaccine doses received into an unvaccinated group: a one-dose group and a two-dose group. The vaccine used was SARS-CoV-2-inactivated vaccine developed by Sinovac. We retrospectively analyzed the patients' epidemiological, clinical, laboratory, and imaging data. RESULTS: Almost all patients with delta-variant infection in Yangzhou were elderly, and patients with severe/critical illness were over 70 years of age. The rates of severe/critical illness (P=0.006), fever (P=0.025), and dyspnea (P=0.045) were lower in the two-dose group than in the unvaccinated group. Compared to the unvaccinated group, the two-dose group showed significantly higher lymphocyte counts and significantly lower levels of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer during hospitalization and a significantly higher positive rate of immunoglobulin G (IgG) antibodies at admission (all P<0.05). The cumulative probabilities of hospital discharge and negative virus conversion were also higher in the two-dose group than in the unvaccinated group (P<0.05). CONCLUSIONS Two doses of the SARS-CoV-2-inactivated vaccine were highly effective at limiting symptomatic disease and reducing immune response, while a single dose did not seem to be effective.
Aged ; Aged, 80 and over ; Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Critical Illness ; Immunity ; Retrospective Studies ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects* ; Viral Vaccines/adverse effects*

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Objective:To investigate the local consistency of inferior colliculus and ventrolateral orbital cortex by resting-state functional magnetic resonance imaging (fMRI) in rats with noise induced deafness and its relationship with anxiety- and depression-like behavior.Methods:Twenty-four clean grade male four-weeks old SD rats were randomly divided into noise group and control group with 12 rats in each group.Rats in the noise group were exposed to 122 dB broadband strong noise for 2 hours to induce severe bilateral hearing loss, while rats in the control group were placed in a quiet environment. Hearing thresholds were assessed by auditory brainstem response (ABR) test. The open field test (OFT) was conducted to examine anxiety-depression related behavior, and the local consistency in the rat brain was evaluated by fMRI.SPM12 software was used to process fMRI data, and Pearson correlation analysis was conducted by SPSS 22.0 software to calculate the correlation between fMRI data and behavior.Results:The results of ABR showed that the full band hearing threshold of rats in the noise group was higher than that of rats in the control group ((85.417±6.463) dB, (20.083±8.853) dB, t=46.168, P<0.001). And compared with control group, the rats in the noise group showed obvious anxiety-depression-like behavior in the open field test, that was, low activity level.The results of OFT showed that the total distance ((39.912±5.696) m, (47.993±10.820)m, t=-2.289, P=0.032), average moving speed ((13.306±1.900)cm/s, (15.998±3.607)cm/s, t=-2.290, P=0.032) and standing times ((13.333±5.960), (23.500±7.323), t=-3.730, P=0.001) of the rats in the noise group were all lower than those in the control group. Compared with the control group, the local consistency of hypothalamus in the noise group was significantly enhanced, while the local consistency of ventrolateral orbital cortex was significantly reduced, and the abnormal neural activity was lateralized. The correlation analysis showed that the neural activity of the inferior colliculus was negatively correlated with the total distance of rats in the noise group moving in the open field( r=-0.691, P=0.013), while the neural activity of the ventrolateral orbital cortex was not significantly correlated with the anxiety-depression-like behavior in the open field. Conclusions:The neural activity of inferior colliculus is closely related to anxious-depression behavior in rats with noise-induced deafness, while the ventrolateral orbital cortex may be related with other behaviors.