OBJECTIVES: To investigate the role of sphingosine-1-phosphate receptor 5 (S1PR5) in modulating barrier function of mouse brain microvascular endothelial cells with oxygen-glucose deprivation and reoxygenation (OGD/R). METHODS: Mouse brain microvascular endothelial cells (bEnd.3) were exposed to OGD/R to induce barrier dysfunction following treatment with S1PR5-specific agonist A971432 or lentivirus-mediated transfection with a S1PR5-specific siRNA, a S1PR5-overexpressing plasmid, or their respective negative control sequences. The changes in viability and endothelial barrier permeability of the treated cells were evaluated with CCK-8 assay and FITC-dextran permeability assay; the levels of intracellular reactive oxygen species (ROS) and localization and expression levels of the proteins related with barrier function and oxidative stress were detected using immunofluorescence staining, DCFH-DA probe and Western blotting. RESULTS: S1PR5 activation obviously enhanced viability of bEnd.3 cells exposed to OGD/R (P<0.0001). Both activation and overexpression of S1PR5 reduced FITC-dextran leakage, while S1PR5 knockdown significantly increased FITC-dextran leakage in the exposed bEnd.3 cells. Activation and overexpression of S1PR5 both increased the cellular expressions of the barrier proteins ZO-1 and occludin, while S1PR5 knockdown produced the opposite effect. In cells exposed to OGD/R, ROS production was significantly reduced by S1PR5 activation and overexpression but increased following S1PR5 knockdown. Overexpression of S1PR5 obviously increased the expressions of the antioxidant proteins Nrf2, HO-1 and SOD2 in the exposed cells. CONCLUSIONS S1PR5 activation and overexpression significantly improve cell viability and reduce permeability of a mouse brain microvascular endothelial cell model of OGD/R, the mechanism of which may involve the reduction in ROS production and upregulation of the antioxidant proteins.
Animals ; Mice ; Oxidative Stress ; Endothelial Cells/cytology* ; Brain/blood supply* ; Reactive Oxygen Species/metabolism* ; Receptors, Lysosphingolipid/metabolism* ; Sphingosine-1-Phosphate Receptors ; Blood-Brain Barrier/metabolism* ; Glucose ; Cell Line ; Oxygen/metabolism* ; NF-E2-Related Factor 2/metabolism*

OBJECTIVE To quantitatively evaluate the effect on decolonization of gram-negative bacteria(GNB)and carbapenem-resistant gram-negative bacteria(CRGNB)in water sinks of neonatal wards and compare the decoloni-zation effects among the 500 mg/L,1000 mg/L of chlorine-containing disinfectants and 3％hydrogen peroxide so-lution.METHODS A total of 15 water sinks were chosen from West China Second University Hospital of Sichuan University as the research subjects,which were randomly divided into the 500 mg/L chlorine-containing disinfect-ant group,the 1000 mg/L chlorine-containing disinfectant group and the 3％hydrogen peroxide solution group.The bacterial colony counts of GNB and CRGNB as well as microbial diversity at the drain outlets were ob-served and compared before the intervention and after the disinfectants were continuously poured for 7 days.RESULTS There were GNB and CRGNB colonized at the drain outlets of water sinks in the neonatal wards under the mode of regular rinsing with 500 mg/L of chlorine-containing disinfectant,with Pseudomonadaceae dominant.There were no significant differences in the bacterial colony counts of GNB/CRGNB,Alpha diversity(Shannon index)and Beta diversity(Bray-Curtis distance)among the three types of disinfectants after the inter-vention for 7 days.CONCLUSIONS There are still large quantity of GNB and CRGNB colonized at the drain outlets of water sinks of neonatal wards after daily conventional treatment with 500 mg/L of chlorine-containing disinfect-ant.Neither the disinfectant with the concentration of chlorine increasing to 1000 mg/L nor 3％hydrogen peroxide solution can remarkably reduce the colonization or alter the microbial diversity.The optimal disinfection strategy should be formulated based on compound disinfectant,physical intervention and project reconstruction.

OBJECTIVE To quantitatively evaluate the effect on decolonization of gram-negative bacteria(GNB)and carbapenem-resistant gram-negative bacteria(CRGNB)in water sinks of neonatal wards and compare the decoloni-zation effects among the 500 mg/L,1000 mg/L of chlorine-containing disinfectants and 3％hydrogen peroxide so-lution.METHODS A total of 15 water sinks were chosen from West China Second University Hospital of Sichuan University as the research subjects,which were randomly divided into the 500 mg/L chlorine-containing disinfect-ant group,the 1000 mg/L chlorine-containing disinfectant group and the 3％hydrogen peroxide solution group.The bacterial colony counts of GNB and CRGNB as well as microbial diversity at the drain outlets were ob-served and compared before the intervention and after the disinfectants were continuously poured for 7 days.RESULTS There were GNB and CRGNB colonized at the drain outlets of water sinks in the neonatal wards under the mode of regular rinsing with 500 mg/L of chlorine-containing disinfectant,with Pseudomonadaceae dominant.There were no significant differences in the bacterial colony counts of GNB/CRGNB,Alpha diversity(Shannon index)and Beta diversity(Bray-Curtis distance)among the three types of disinfectants after the inter-vention for 7 days.CONCLUSIONS There are still large quantity of GNB and CRGNB colonized at the drain outlets of water sinks of neonatal wards after daily conventional treatment with 500 mg/L of chlorine-containing disinfect-ant.Neither the disinfectant with the concentration of chlorine increasing to 1000 mg/L nor 3％hydrogen peroxide solution can remarkably reduce the colonization or alter the microbial diversity.The optimal disinfection strategy should be formulated based on compound disinfectant,physical intervention and project reconstruction.

Objective To explore the key genes and long non-coding RNAs(lncRNAs)associated with Parkinson's disease(PD).Methods Peripheral blood plasma samples were collected from 6 PD patients and 6 healthy individuals.The mRNA and lncRNA expression profiles were detected using ceRNA microarray technology,and the differentially expressed genes were analyzed using bioinformatics methods.The differentially expressed mRNAs transcribed within 10 kb upstream or downstream of the differentially expressed lncRNAs were defined as potential cis-regulatable(Cis)target genes of the lncRNAs.A PD-specific protein-protein interaction network(PPI)was constructed.Competitive endogenous RNA(ceRNA)networks were also constructed using the differential lncRNAs with mRNAs and known microRNAs.Using MPP+-treated SH-SY5Y cells as a PD cell model,the expressions of the key lncRNAs and their functions were examined.Results We identified 316 genes and 986 lncRNAs showing significant differential expressions in PD patients(P<0.05).The differentially expressed mRNAs and the potential cis-regulatable target genes of these lncRNAs were functionally annotated using GO and KEGG enrichment analysis,and the targeting relationship of the differentially expressed mRNAs and lncRNAs with microRNAs were predicted.Analysis of the ceRNA networks constructed based on the differentially expressed lncRNAs suggested that lnc-MTG2-1:1,lnc-CTSD-5:1,lnc-PCCA-3:1,lnc-VTCN1-3:1,lnc-ZNF25-7:1,and lnc-DAZ3-1:1 might be the key lncRNAs in PD.In MPP+-treated SH-SY5Y cells,the expression of lnc-CTSD-5:1 showed the most significant changes,and silencing lnc-CTSD-5:1 obviously restored the expression level of tyrosine hydroxylase.Conclusion PD patients have significant changes in plasma lncRNA expression profile,and the differentially expressed genes and lncRNAs found in this study may provide new clues for exploring the pathogenesis and identifying potential biomarkers of PD.

Objective To explore the key genes and long non-coding RNAs(lncRNAs)associated with Parkinson's disease(PD).Methods Peripheral blood plasma samples were collected from 6 PD patients and 6 healthy individuals.The mRNA and lncRNA expression profiles were detected using ceRNA microarray technology,and the differentially expressed genes were analyzed using bioinformatics methods.The differentially expressed mRNAs transcribed within 10 kb upstream or downstream of the differentially expressed lncRNAs were defined as potential cis-regulatable(Cis)target genes of the lncRNAs.A PD-specific protein-protein interaction network(PPI)was constructed.Competitive endogenous RNA(ceRNA)networks were also constructed using the differential lncRNAs with mRNAs and known microRNAs.Using MPP+-treated SH-SY5Y cells as a PD cell model,the expressions of the key lncRNAs and their functions were examined.Results We identified 316 genes and 986 lncRNAs showing significant differential expressions in PD patients(P<0.05).The differentially expressed mRNAs and the potential cis-regulatable target genes of these lncRNAs were functionally annotated using GO and KEGG enrichment analysis,and the targeting relationship of the differentially expressed mRNAs and lncRNAs with microRNAs were predicted.Analysis of the ceRNA networks constructed based on the differentially expressed lncRNAs suggested that lnc-MTG2-1:1,lnc-CTSD-5:1,lnc-PCCA-3:1,lnc-VTCN1-3:1,lnc-ZNF25-7:1,and lnc-DAZ3-1:1 might be the key lncRNAs in PD.In MPP+-treated SH-SY5Y cells,the expression of lnc-CTSD-5:1 showed the most significant changes,and silencing lnc-CTSD-5:1 obviously restored the expression level of tyrosine hydroxylase.Conclusion PD patients have significant changes in plasma lncRNA expression profile,and the differentially expressed genes and lncRNAs found in this study may provide new clues for exploring the pathogenesis and identifying potential biomarkers of PD.

Septic shock has always been a challenging problem for people,with a high incidence rate and mortality.After decades of development,significant progress has been made in the pathophysiology and clinical aspects of septic shock.The"Surviving Sepsis Campaign"guidelines provide a suitable approach to directing treatment,enabling earlier recognition of septic shock and reducing its mortality rate.However,there are still many challenges,such as refractory septic shock(RSS)and multiple organ failure.Over the past decade,extracorporeal membrane oxygenation(ECMO)technology has been increasingly applied in the treatment of critically ill patients.Whether ECMO can be considered as a salvage treatment for RSS is increasingly being considered.This report presents the experience of successfully treating a patient with RSS using ECMO in our department.For the management of RSS,it is recommended to consider ECMO as a worthwhile option,providing some practical experience for the treatment of RSS with ECMO.

Objective To analyze the causes of acute intestinal obstruction after intracerebral hemorrhage,and the therapeutic effect of rectal dripping with Dachengqi decoction and Fusu agent on acute intestinal obstruction complicated with septic shock.Methods The clinical data of a patient with acute intestinal obstruction complicated with septic shock after intracerebral hemorrhage,who was admitted to the Hospital of Chengdu University of Traditional Chinese Medicine(TCM)on March 5,2022,were retrospectively analyzed.The study aimed to observe the effects of rectal dripping with TCM on the recovery of intestinal function and improvement of shock.Results The patient was a 52-year-old male who underwent"left temporal craniotomy intracranial decompression,craniocerebral hematoma removal,cerebrospinal fluid leak repair"on February 19,2022 due to cerebral hemorrhage.On the 7th day after operation,the patient had hiccups and abdominal distension,and after treatment,the patient developed fever,consciousness disorders,hypotension and other symptoms.Abdominal CT showed extensive intestinal fluid,gas and expansion.Hemodynamic monitoring indicated high discharge and low resistance,intra-abdominal pressure was 21 cmH2O(1 cmH2O≈0.098 kPa),and laboratory examination showed increased inflammatory indexes and abnormal biochemical indexes.The western medicine diagnosis was acute intestinal obstruction complicated with septic shock,and the symptomatic treatments such as organ support(lung,circulation,kidney),anti-infection,fluid resuscitation,analgesia and sedation were given.The TCM diagnosis was intestinal knot(yangming visceral substantive,sudden collapse of yang-qi),with treatment principles focusing on tongfu heat relief,wenshen qianyang,Dachengqi decoction and Fusu agent was added and reduced according to the syndrome differentiation,with medications administered rectally.After the use of TCM decoction,the patient's defecation volume increased significantly,the intra-abdominal pressure decreased to the normal range,abdominal distension was significantly reduced,and the shock was relieved.On the 17th day after the operation,the patient's symptoms improved,the respiratory cycle was stable,and the patient was successfully transferred out of intensive care unit(ICU).Conclusion The treatment of acute intestinal obstruction complicated with septic shock by rectal dripping with Dachengqi decoction and Fusu agent can quickly relieve the condition and promote the recovery of intestinal function.

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.

AIM:To explore the impact of sphingosine 1-phosphate receptor 5(S1PR5)on lipopolysaccha-ride(LPS)-induced neuroinflammation and cognitive-behavioral impairments in mice,alongside the anti-inflammatory im-pacts on BV2 cells and associated mechanisms.METHODS:(1)C57BL/6 wild-type(WT)mice and homozygous S1PR5 knockout(KO)mice were utilized and categorized into WT control,WT-LPS,S1PR5 KO control,and S1PR5 KO-LPS groups using the random number method.Neuroinflammatory models in mice were induced by a single intraperitoneal injection of 5 mg/kg LPS in the WT-LPS and S1PR5 KO-LPS groups,while an equivalent volume of saline was injected in-to the WT control and S1PR5 KO control groups.Following 7 days of modeling,the Morris water maze test was conducted,followed by the collection of brain tissues from each group of mice.Hippocampal tissue sections were stained with Nissl.The mRNA expression levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in hippocampal tis-sues were determined using RT-qPCR.Western blot and tissue immunofluorescence techniques were employed to assess the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in hippocampal tissues.(2)The BV2 cells underwent LPS stimulation to induce an inflammatory response and were treated with either the S1PR5 ago-nist A971432 or lentiviral overexpression of S1PR5.The effects of S1PR5 agonism or overexpression on S1PR5,IL-1β,IL-6,TNF-α,and CD206 were assessed using RT-qPCR.Additionally,CD206 expression was examined via cellular im-munofluorescence.Western blot was employed to analyze the protein levels of microglia polarization markers CD206,in-ducible nitric oxide synthase(iNOS),cyclooxygenase 2(COX2),and NLRP3,as well as p-NF-κB,cleaved caspase-1,and IκBα.RESULTS:(1)Findings from in vivo experiments indicated that S1PR5 KO notably exacerbated LPS-induced memory impairments in mice,alongside increased mRNA levels of IL-1β and IL-6,and increased protein levels of NLRP3 in the hippocampus.(2)The presence of S1PR5 in BV2 cells remained unaffected by variations in A971432 concentration and exposure duration.(3)Activation of S1PR5 or its overexpression significantly mitigated LPS-induced expression of IL-1β,IL-6,and TNF-α,while concurrently enhancing CD206 expression in BV2 cells at the mRNA level.At the protein level,it led to a noteworthy increase in CD206 expression,indicative of M2-type macrophages,and a reduction in the ex-pression of iNOS and COX2,markers of M1-type macrophages.Furthermore,it downregulated NLRP3,p-NF-κB,and cleaved caspase-1 expression,while upregulating IκBα expression.CONCLUSION:S1PR5 deficiency exacerbates cog-nitive deficits in mice by promoting neuroinflammatory responses induced by LPS.

Background: and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. Methods: This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. Results: Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). Conclusion In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.