Objective To investigate the effect of microglia activation regulated by C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1)pathway on memory function in hemorrhagic shock/resuscitation rats.Methods The experiment was divided into two parts.In the first part,the rats were randomly divided into sham group,model-0.5 hour group,model-1.5 hour group,model-3 hour group,10 rats in each group.There were differences in the time of hemorrhagic shock among each group.In the second part,rats were randomly divided into control group and CX3CL1 group,10 rats in each group.The rats in CX3CL1 group were treated with CX3CL1 protein factor(intraventricular injection),and the rats in control group were treated with saline.All rats were trained in Morris water maze experiments before model construction,and tests of Morris water maze experiments were carried out after 4 days of model construction.After completion,the whole brains were taken for HE staining and immunohistochemical staining.Cerebrospinal fluid was taken for detection of inflammatory cytokines,and hippocampus tissues were taken for Real-time PCR detection and Western blotting detection.Results Compared with the sham group,the escape latency of rats in model group increased,the number of platform crossings and the resident time in the third quadrant decreased.The neuronal state was impaired in HE staining in model group.In addition,compared with the sham group,the expression of ionized calcium binding adaptor molecule-1(Iba1)in the brain of the rats in model group increased,the contents of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the cerebrospinal fluid increased,and the M1-type microglia markers CD16,TNF-α,IL-1β and inducible nitric oxide synthase(iNOS)mRNA content increased.At the same time,compared with the sham group,the expressions of CX3CL1 and CX3CR1 in the brain of model group decreased,and the expressions of phosphorylated nuclear factor-κB(p-NF-κB)and nucleotide binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)increased.However,compared with the control group,rats in CX3CL1 group had reduced escape latency,increased platform crossing times and quadrantⅢresident time,and recovered neuronal states.In addition,the expression of Iba1 in the brain of CX3CL1 group decreased,the contents of TNF-α and IL-6 in the cerebrospinal fluid decreased,the mRNA contents of M1-type microglia markers like CD16,TNF-α,IL-1β and iNOS decreased,and the mRNA contents of markers of M2-type microglia glial like CD206,transforming growth factor-β(TGF-β),arginase-1(Arg1),Chitinase 3-like protein 1(Ym 1)increased.Conclusion CX3CL1 can help inhibit the excessive activation of microglia,induce the polarization of microglia to M2 type,inhibit the polarization of M1 type,reduce the release of inflammatory cytokines,and alleviate the memory function damage induced by hemorrhagic shock/resuscitation.

Objective This study analyzes the omics data resources in human-infecting coronavirus animal models collected from various public databases,focusing on data distribution,dataset quantity,data types,species,strains,and research content.It aims to enhance our understanding of biological characteristics and pathogenic mechanisms of coronaviruses,thereby providing a solid foundation for devising effective therapeutic strategies and preventive measures.Methods Query strategies,including specific virus names,time ranges,and inclusion and exclusion criteria,were defined to retrieve data from major public omics databases such as GEO and ArrayExpress.Secondary filtering was performed based on different field types to obtain a more accurate data list.An omics data text database was established for bibliometric analysis.Co-occurrence networks were constructed for the analysis of the correlation strengths between different research themes,technical methods,and involved species.The cell types,organs,and biological pathways involved in studies were examined to further elucidate the pathogenic interplay between pathogens and hosts.Results About twenty public databases containing coronavirus-related omics data were identified,with a primary focus on novel coronavirus infection.Commonly used species include humans,mice,hamsters,and monkeys,while the commonly used virus strains are Wuhan-Hu-1 and USA-WA1/2020.Lung tissues are primarily used in animal models such as mice,macaques,and ferrets,while airway epithelial cells and Calu-3 cells are predominantly employed in human-related studies.Expression profiling data indicate that gene pathways involved in inflammation,cytokine response,complement pathway,cell damage,proliferation,and differentiation are significantly upregulated after infection.Proteomics studies reveal significant changes in phosphoproteome,ubiquitinome,and total proteome of patient samples at different infection stages.Specific protein categories,including viral receptors and proteases,transcription factors,cytokines,proteins associated with coagulation system,angiogenesis-related proteins,and fibrosis markers,show alterations after coronavirus infection.In addition,metabolomics data suggest that phosphocholine,phosphoethanolamine,arachidonic acid,and oleic acid could serve as potential metabolic markers.Epigenomics research indicates m6A methylation plays a role in SARS-CoV-2 replication,infection,and transmission,affecting host cell-virus interactions.Among these,N,S,and non-structural proteins 2 and 3 exhibit the most significant ubiquitination.Trends in microbiomics research suggest that microbial communities in the gut and wastewater are emerging as new research focuses.Conclusion The data types of coronavirus omics are diverse,with a wide variety of models and cell types used.The selection of species and technical methods for modelling varies based on the characteristics of different viruses.Multi-omics data from animal models of coronavirus infection can reveal key interactions between hosts and pathogens,identifying biomarkers and potential therapeutic targets,and provide valuable information for a deeper understanding of biological characteristics and infection mechanisms of coronaviruses.

The interaction between Mycobacterium tuberculosis and host, as well as the regulation of some signaling pathways in the host, were involved in pathogen latency in macrophages. microRNAs (miRNAs) regulate the gene expression and biological functions, indicating that miRNAs played a regulatory role in bacterial infections. However, whether the host's miRNAs were also involved in the process of Mycobacterium tuberculosis infection had not been thoroughly studied. This study infected macrophages with pathogenic Mycobacterium tuberculosis strain H37Rv and low virulence strain H37Ra to explore the functional miRNAs. By identifying the expression profile of miRNAs in host cells after infection, the expression of 17 miRNAs significantly changed (P < 0.05) in the human macrophage THP-1 infected with highly pathogenic H37Rv strain (Rv), H37Rv inactivated strain (Rv-), and non-pathogenic H37Ra (Ra) strains respectively, indicating that host miRNAs may be involved in the interaction of Mycobacterium tuberculosis and host. Meanwhile, 10 types of miRNAs showed significant differences in cells infected with pathogenic and non-pathogenic Mycobacterium tuberculosis, suggesting that host miRNAs may play an important role in the pathogenicity and intracellular survival of Mycobacterium tuberculosis. Further study had found that miR-449a, miR-502-5p, and miR-708 were downregulated in cells infected with Mycobacterium marinum. Overexpression of these three miRNAs displayed the significant inhibitory effect on the growth of Mycobacterium marinum, indicating that miRNAs played a pivotal role in the interaction between the host and Mycobacterium marinum. This study provided the new insights into the pathogenesis of Mycobacterium tuberculosis and the treatment of tuberculosis.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

HDAC(histone deacetylase)is a class of epigenetic modifying enzymes that can deacetylate proteins by altering the acetylation status of histones in the nucleus,regulating promoter activation levels,and thereby affecting downstream gene expression.However,expression changes of HDACs during endo-thelial differentiation are still unclear.This study used a three-stage method to induce human induced pluripotent stem cells(hiPSCs)to differentiate into endothelial cells,and qRT-PCR was used to detect the expression changes of class I HDAC(HDAC1,2)and class Ⅱ HDAC(HDAC4,5)genes.It was found that HDAC5 exhibits significant expression changes during endothelial differentiation.It is downreg-ulated by 90％during the mesodermal differentiation stage(P＜0.01),upregulated by 3.7-fold during the vascular precursor stage(P＜0.01),and subsequently downregulated by 70％during the late stage of endothelial differentiation(P＜0.01).Immunoblotting experiments further confirmed that HDAC5 under-goes periodic expression changes during endothelial differentiation.Mechanistic studies have shown that HDAC5 downregulation during the differentiation stage of the mesoderm is mediated by Wnt signaling.CHIR99021 treatment and overexpression of Wnt3a can activate the Wnt signaling pathway,leading to HDAC5 downregulation.Inhibiting the Wnt signaling pathway through IWP-2 promotes the recovery of HDAC5 expression.In addition,it was found that HDAC5 is mainly localized in the nucleus,and IWP-2 restores HDAC5 expression,but it remains in the cytoplasm.Further research suggests that downregu-lation of HDAC5 during mesodermal differentiation may contribute to the expression of the mesodermal marker BraT.Treatment with the HDAC inhibitor BML210 can promote early mesodermal differentiation,interfere with endothelial differentiation of vascular precursor cells,and enhance late-stage endothelial differentiation.In conclusion,HDAC5 displays a stage-specific expression during endothelial differentia-tion,and Wnt signaling activation is the main mechanism regulating the downregulation of HDAC5 during the mesoderm stage.

Post-stroke cognitive impairment(PSCI)is a prevalent functional impairments following stroke that seriously affects patients'quality of life and daily activities.Studies indicate a close relationship between intestinal microflora dysbiosis and central nervous system diseases.Intestinal microflora profoundly impacts on human physiological health,contributing to the stability of nervous,metabolic and immune systems through regulation of the gut-brain axis.An increasing number of studies confirmed the important role of the gut microbiome-gut-brain axis in the occurrence and development of stroke and its associated PSCI,and regulation of microbiome-gut-brain could be potential target to treatment of PSCI.This review summarizes research progress on gut microbiome-gut-brain axis and PSCI to provide a reference for exploration of related mechanisms and clinical prevention and treatment strategies.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To analyze associated factors and adverse pregnancy outcomes of postpartum hemorrhage in the caesarean section of puerperae with different types of placenta previa. Methods: This retrospective research was a case-control study. Puerperae with cesarean section of placenta previa from January 2019 to December 2020 in Women's Hospital, School of Medicine, Zhejiang University were collected and divided into the<1 000 ml control group or ≥1 000 ml postpartum hemorrhage group according to the amount of blood loss during cesarean section. Differences in continuous variables were analyzed by t-test and categorical variables were analyzed by χ² test. The risk factors of postpartum hemorrhage were analyzed by logistic multivariate regression. Results: A total of 962 puerperae were enrolled with 773 cases in the control group and 189 cases in the postpartum hemorrhage group. The incidence of gestational weeks, gravidity, parity, induced abortion, placental accreta and preoperative hemoglobin<110 g/L was significantly different between two groups in different types of placenta previa (P<0.001). Logistic multivariate regression model analysis showed that the independent risk factors of postpartum hemorrhage in the caesarean section of low-lying placenta included placental accreta (OR=12.713, 95%CI: 4.296-37.625), preoperative hemoglobin<110 g/L (OR=2.377, 95%CI: 1.062-5.321), and prenatal vaginal bleeding (OR=4.244, 95%CI: 1.865-9.656). The independent risk factors of postpartum hemorrhage in the caesarean section of placenta previa included once induced abortion (OR=2.789, 95%CI:1.189-6.544), induced abortion≥2 (OR=2.843, 95%CI:1.101-7.339), placental accreta (OR=6.079, 95%CI:3.697-9.996), HBsAg positive (OR=3.891, 95%CI:1.385-10.929), and placental attachment to the anterior uterine wall (OR=2.307, 95%CI:1.285-4.142). The rate of postpartum hemorrhage and premature delivery in puerperae with placenta previa was higher than that in puerperae with low-lying placenta (P<0.001). Conclusions: The associated factors of postpartum hemorrhage in puerperae with different types of placenta previa are different. Placenta accreta is the common risk factor of postpartum hemorrhage in puerperae with low-lying placenta and placenta previa.
Female ; Pregnancy ; Humans ; Cesarean Section ; Postpartum Hemorrhage/surgery* ; Pregnancy Outcome ; Retrospective Studies ; Case-Control Studies ; Placenta Previa/surgery* ; Placenta ; Risk Factors

OBJECTIVES: To compare the efficacy of needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training in the treatment of post-stroke cognitive impairment (PSCI). METHODS: A total of 206 patients with PSCI were randomized into a needle retaining group (103 cases, 9 cases dropped out) and an electroacupuncture group (103 cases, 6 cases dropped out). In addition to the conventional basic medical treatment and the rehabilitation treatment, in the needle retaining group, electroacupuncture at Shenting (GV 24) and Baihui (GV 20) was applied, with continuous wave of 50 Hz in the first 15 min and with disperse-dense wave of 2 Hz/50 Hz in the last 15 min, the needles were continuously retained for 1 h after electroacupuncture, during which cognitive training was adopted; in the electroacupuncture group, cognitive training was performed after the same electric stimulation exerted for 30 min, without additional needles retaining. The treatment was given once a day, 5 times a week for totally 8 weeks in the two groups. Before and after 8-week treatment, the TCM syndrome score was observed; before and after 4,8-week treatment, the scores of mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and ability of daily living were observed in the two groups. The clinical efficacy of the two groups was evaluated after 8-week treatment. RESULTS: After 8-week treatment, the TCM syndrome scores were increased compared with those before treatment in both groups (P<0.05); the TCM syndrome score in the needle retaining group was higher than that in the electroacupuncture group (P<0.05).After 4,8-week treatment, the scores of MMSE, MoCA and ability of daily living were increased compared with those before treatment in both groups (P<0.05); MMSE, MoCA scores after 4,8-week treatment and ability of daily living score after 8-week treatment in the needle retaining group were higher than those in the electroacupuncture group (P<0.05). The total effective rate was 90.4% (85/94) in the needle retaining group, which was superior to 82.5% (80/97) in the electroacupuncture group (P<0.05). CONCLUSIONS Both needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training can effectively treat PSCI, improve the clinical symptom, cognitive function and ability of daily living in PSCI patients. Needle retaining after electroacupuncture combined with cognitive training has a better therapeutic effect.
Humans ; Electroacupuncture ; Acupuncture Therapy ; Cognitive Training ; Acupuncture Points ; Cognitive Dysfunction/therapy* ; Stroke/complications* ; Treatment Outcome