The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Objective To investigate the neuroprotective effect of 7,8-dihydroxyflavone(7,8-DHF)on cerebral hemorrhage in mice by regulating the tyrosine kinase receptor B(TrkB)/brain derived neurotrophic factor(BDNF)signal pathway.Methods C57BL/6 mice were injected with bacterial collagenase V Ⅱ to establish cerebral hemorrhage model.The mice were randomly grouped into model group,control group(5 mg·kg-1 7,8-DHF),experimental group(1 mg·kg-1 K252a),and combined group(5 mg·kg-1 7,8-DHF+1 mg·kg-1 K252a),mice injected with normal saline were used as sham-operation group,with 10 mice in each group.After the treatment,the mice were scored for neurological function by Garcia method,brain water contents of the brain tissue were detected by the dry and wet weight method,the blood brain barrier permeability was examined using the Evans blue method,the neuronal apoptosis was detected by TUNEL method,and the protein expression levels of TrkB,phosphorylated TrkB(p-TrkB)and BDNF were detected by Western blot.Results The neurological function scores of control,experimental,combined,model and sham-operation groups were(15.47±1.55),(7.23±0.73),(10.55±1.06),(10.45±1.05)and(16.12±1.62)points;the brain water contents were(62.88±2.19)％,(83.77±3.11)％,(72.71±2.59)％,(72.88±2.61)％and(59.64±2.06)％;the Evans blue contents were(3.26±0.36),(16.23±1.63),(8.78±0.88),(9.47±0.95)and(1.02±0.11)μg·g-1;neuronal apoptosis rates were(9.82±0.99)％,(39.88±3.99)％,(22.15±2.24)％,(25.71±2.58)％and(6.46±0.65)％;p-TrkB/TrkB ratios were 1.01±0.11,0.21±0.03,0.48±0.05,0.49±0.05 and 1.03±0.11;the protein expression levels of BDNF were 1.15±0.12,0.18±0.02,0.46±0.05,0.42±0.05 and 1.18±0.12,respectively.The above indexes of sham-operation,control and experimental groups were compared with those of model group,and the above indexes of control and experimental groups were compared with those of combined group,the differences were statistically significant(all P＜0.05).Conclusion 7,8-DHF has neuroprotective effect on mice with intracerebral hemorrhage,and its mechanism may be related to the activation of TrkB/BDNF signal pathway.

Objective To quantitatively assess the influence of various factors on the pharmacokinetic parameters of propofol and to develop a propofol population pharmacokinetic model tailored for Chinese patients.Methods Thirty patients scheduled for selective abdominal surgeries received an anesthesia dose of propofol at 2.0 mg·kg-1.The concentration of propofol in collected venous blood samples was measured using liquid chromatography-tandem mass spectrometry.Polymorphisms in metabolizing enzyme genes were detected through Sanger sequencing technology.Pharmacokinetic parameters were computed,and models were constructed and evaluated using Phoenix Winnonlin software.Results Through software analysis,the drug's in vivo process was best described by a three-compartment model.The population mean values for the central compartment clearance rate(CL),shallow peripheral compartment clearance rate(Q2),deep peripheral compartment clearance rate(Q3),central compartment volume of distribution(V),shallow peripheral compartment volume of distribution(V2),and deep peripheral compartment volume of distribution(V3)were 1.71 L·min-1,1.31 L·min-1,1.51 L·min-1,5.92 L,19.86 L and 99.06 L,respectively.Body weight was identified as a significant covariate affecting CL and V,and was incorporated into the model.Conclusion The evaluation of the final model demonstrates its substantial predictive capability,offering directional guidance for the clinical administration of propofol.

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Objective To investigate the differentially expressed genes(DEGs)and their molecular interactions in unstable carotid atherosclerotic plaques.Methods Gene expression datasets related to carotid atherosclerotic plaques(GSE41571,GSE118481,and E-MTAB-2055)were downloaded from Gene Expression Omnibus(GEO)and European Bioinformatics Institute(EBI)ArrayExpress databases.The co-regulated DEGs in at least two datasets of unstable carotid plaques were merged and analyzed using Gene Ontology Biological Process(GO-BP),Kyoto Encyclopedia of Genes and Genomes(KEGG),Protein-Protein Interaction(PPI)Networks and subnetwork analysis,relationships between miRNAs/transcription factors and target genes,and drug-gene interaction database.Quantitative real-time PCR(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to detect the expression levels of some DEGs in carotid plaques and plasma from 58 patients with carotid atherosclerosis.Results GO enrichment analysis showed that DEGs in unstable carotid atherosclerotic plaques were mainly enriched in genes related to inflammatory response and extracellular matrix structure genes.KEGG enrichment analysis indicated that upregulated DEGs in unstable carotid plaques were enriched in extracellular matrix receptor(ECM-receptor)interaction,PI3K-Akt,Hippo and transforming growth factor-β(TGF-β)signaling pathways,while downregulated DEGs were primarily enriched in lysosomes,phagosomes,and chemokines processes.PPI network analysis suggested that COL1A2,COL4A2,insulin-like growth factor binding protein 6(IGFBP6),COL4A5,C1QA,CXCL10,CXCL2,CXCR4,and CSF1R may play important roles in PPI networks.Prediction of drug-gene interactions revealed that CSF1R had the most drug interaction,CXCL2 was most antagonized by drugs,and IGFBP6 was most activated by drugs.qRT-PCR showed that the expression level of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group(P<0.001).ELISA results showed that plasma concentration of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group(P<0.0001).Receiver operating characteristic(ROC)suggested that the area under the curve(AUC)for plasma IGFBP6 levels to identify unstable plaques was 0.894(95%CI 0.810-0.977),with a cutoff value of 142.08 ng/ml.Conclusion IGFBP6 may become an important biomarker for predicting unstable carotid atherosclerotic plaques.

Objective:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

As a normal physiological substance,D-galactose can induce a process similar to natural brain aging in vivo and in vitro when administered excessively,and thus it is widely used to induce brain aging models in China and abroad.The model of brain failure induced by D-galactose has the advantages of a short modeling time,low cost,and significant effect.However,the induction mechanisms are complex and diverse,and the relationships between the mechanisms are unclear,which limit the practical applications of the model.This article reviews the in vivo metabolism of D-galactose and the various mechanisms involved in the induction of brain aging,as well as the links between the mechanisms,to provide a reference for the application and development of this model and the in-depth study of brain aging.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.