To investigate the genetic relatedness between carbapenem-resistant Klebsiella pneumoniae(CRKP) strains isolated from intestinal colonization and subsequent bloodstream infections.

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

OBJECTIVES: This study aimed to explore the potential target and molecular mechanism of Eclipta prostrata L-Ligustrum Lucidum Ait (EPL-LLA) in the treatment of periodontitis by using network pharmacology and molecular docking technology, and to explore its biocompatibility, regulatory effects on inflammatory factors, and antioxidant acti-vity through in vitro experiments. METHODS: The active components and potential targets of EPL-LLA were screened and predicted through a variety of databases, and the intersection of EPL-LLA and periodontitis targets was selected. The protein interaction network (PPI) was analyzed by the string platform. The Metascape database was used for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The active ingredients from the top 6 degrees were docked with the core targets, and the results of binding energy were visualized. An in vitro cell model was established to evaluate the biocompatibility, modulation of inflammatory factors, and antioxidative effects of EPL-LLA through cell counting kit-8 (CCK-8), quantitative real-time polymerase chain reaction (qRT-PCR) and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe assays. RESULTS: Screening revealed 13 active components in EPL corresponding to 220 potential targets, 10 active components in LLA corresponding to 283 potential targets, and 1 643 periodontitis-related targets, with 91 shared targets among the three. GO analysis of the shared targets yielded 5 271 entries, while KEGG enrichment analysis indicated involvement in 253 signaling pathways. Molecular docking confirmed stable binding between the top 6 active components and core targets. CCK-8 assays demonstrated good biocompatibility of EPL-LLA at concentrations 0.02 mg/mL (P<0.05). qRT-PCR showed that EPL-LLA reduced the mRNA expression of pro-inflammatory factors in macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide while upregulating anti-inflammatory factor mRNA expression (P<0.05). DCFH-DA fluorescence probe assays confirmed the reactive oxygen species (ROS)-scavenging capacity of EPL-LLA (P<0.05). CONCLUSIONS EPL-LLA may treat periodontitis through multi-component, multi-target, and multi-pathway mechanisms, providing a theoretical basis for further research on its therapeutic potential.
Periodontitis/drug therapy* ; Molecular Docking Simulation ; Eclipta/chemistry* ; Humans ; Protein Interaction Maps ; Ligustrum/chemistry* ; Antioxidants/pharmacology* ; Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology

Thyroid-associated ophthalmopathy(TAO)is a progressive eye disease characterized by immune-mediated inflammation of the extraocular muscles and orbital connective tissue.TAO tends to have complex and diverse symptoms and signs,with the features of diversity and concealment,which seriously affect the quality of life of patients.The pathogenesis of TAO is closely associated with thyroid autoimmunity.This article reviews the pathogenesis,clinical features,and treatment of TAO.

Objective To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of ginsenoside Rh2(GRh2)in plasma of mice,so as to provide preclinical data support for the pharmacokinetic study and application of GRh2.Methods C57BL16 mice were given 7.5 mg/kg GRh2 by gavage.After administration,0.03 mL of whole blood was collected at 5 min,10 min,15 min,30 min,1 h,2 h,4 h,and 8 h.Then,the whole blood was centrifuged and the serum was treated with 0.1％formic acid acetonitrile,dried by nitrogen(40℃),and redissolved with 50.0 pL 50％methanol solution containing 100 ng/mL diclofenac sodium.After vortex mixing for 5 min at room temperature,it was put into the automatic sampler for sampling analysis.The chromatographic column was Waters BEHC18(2.1 mm × 50.0 mm,1.7 pm),the mobile phase was aqueous solution containing 0.1％formic acid and acetonitrile solution containing 0.1％formic acid at a flow rate of 0.60 mL/min,the column temperature was 40℃,and the injection volume was 1.00 pL.The electric spray ion source,positive ion mode and multiple reaction monitoring mode were performed.A standard curve was established to calculate blood drug concentration.The blood drug concentration-time curve was established according to the blood drug concentration,and the main pharmacokinetic parameters were calculated.Results The linear range of the standard curve of drug containing plasma was 100-40 000 ng/mL,and the correlation coefficient(r)was 0.996 0.After internal standard normalization,the matrix effect factors of GRh2 were 1.09,1.06,and 1.00(between 0.8 and 1.2),indicating no significant matrix effect.The precision and accuracy results showed that the average measured concentration of GRh2 samples at each concentration level was 103,333,23 800 and 35 000 ng/mL,the inter batch standard deviation was 6.47-1 120 ng/mL,the inter batch relative standard deviation was 1.5％-8.3％,and the inter batch accuracy deviation was 93.3％-111.1％.The long-term stability,short-term stability,repeated freeze-thaw property,and extraction recovery rate of GRh2 were all good.The pharmacokinetic parameters Tmax and Cmax of GRh2 in mice were(1.42±1.01)h and(1 251±495)ng/mL,respectively,indicating that the absorption and utilization rate of GRh2 in vivo was high and GRh2 had good drug performance.Conclusion The established LC-MS/MS method is accurate and reliable,and can be used to determine the concentration of GRh2 in mouse plasma and study its pharmacokinetic.

Objective:To investigate the efficacy and prognosis of biliary drainage via endoscopic retrograde cholangiopancreatography (ERCP) before steroid therapy in treating autoimmune pancreatitis (AIP) complicated with obstructive jaundice.Methods:A retrospective analysis was performed on clinical data of patients with AIP complicated with obstructive jaundice who received steroid therapy at the First Affiliated Hospital of Naval Medical University from 2010 to 2023. Patients were divided into a drainage group (receiving ERCP biliary drainage before steroid therapy) and a steroid group (receiving only steroid therapy). Short-term efficacy, long-term efficacy, hospitalization costs and postoperative complications of ERCP biliary drainage were compared between the two groups.Results:A total of 69 patients were included, with 32 in the drainage group, aged 62.78±11.21 years, which demonstrated significantly higher costs (34 816.57±11 688.85 yuan VS 16 518.50±6 544.37 yuan, t=7.0, P<0.001), with 25.00% (8/32) experiencing ERCP-related complications, compared with 37 patients in the steroid group, aged 55.41±2.15 years. There was no significant difference in hospitalization duration between the drainage group (10.38±4.56 days) and the steroid group (8.95±4.99 days, t=1.2, P=0.219). After 1 month of treatment, total bilirubin [118.5 (76.2, 309.3) μmol/L VS 48.7 (30.5, 148.4) μmol/L, U=1 728.5, P<0.001] and direct bilirubin [84.5 (47.7, 236.3) μmol/L VS 37.7 (18.3, 105.7) μmol/L, U=1 588.5, P=0.001] levels in the drainage group remained higher than those in the steroid group, while alanine aminotransferase levels were lower [74.0 (46.5,110.5) U/L VS 143.0 (51.0,253.5) U/L, U=769.0, P=0.006]. No significant differences were observed in these biochemical indices between the two groups at 4-month and 12-month follow-ups ( P>0.05). The recurrence rates were 28.1% (9/32) in the drainage group and 21.6% (8/37) in the steroid group, with no significant difference in recurrence rate between groups ( χ2=0.4, P=0.266). Conclusion:ERCP biliary drainage does not significantly improve long-term efficacy or reduce recurrence rates in AIP patients with obstructive jaundice. Instead, it increases the risk of postoperative complications and medical costs. Direct steroid therapy is safe and feasible for confirmed AIP with obstructive jaundice.

Image 1.

Purpose To explore the clinicopathological features and endoscopic manifestations of cap polyposis(CP).Methods Clinical,endoscopic,pathological,and follow-up data of 17 cases of CP were collected and ana-lyzed.Results There were 14 males and 3 females,aged 15-67 years,with a mean age of 36.5 years.The disease duration ranged from 2 weeks to 5 years,and most patients(64.7％,11/17)had symptoms for more than l year.The most common clinical manifestation was hematochezia(82.4％,14/17),while constipation was generally absent.En-doscopically,all lesions(100％,17/17)were located in the anal canal and lower rectum.The surface was invariably covered with a thick whitish exudate(100％,17/17),and annular growth was the most frequent pattern(76.5％,13/17).Pathologically,the mucosal layer was almost entirely replaced by granulation tissue,and the surface showed extensive inflammatory necrosis forming a cap-like structure.Conclusion CP predominantly occurrs in the anal canal and lower rectum of young men.The presence of abundant whitish exudate under endoscopy is differential diagnostic value.Complete endoscopic resection followed by pathological examination is required for definitive diagnosis.

Objective Five chloroplast(cp)genomes from members of genus Polygonatum were assembled by hybrid assembly technique,and their intraspecic and interspecific differences were analyzed by comparative genomic method.Codon usage patterns and influencing factors were determined,and the cp genome data were applied to understand the phylogenomic relationships in the entire genus Polygonatum along with the available data.Methods In this study,the chloroplast genomes of 5 species of genus Polygonatum were assembled using Unicycler software.Sequence alignment,collinearity analysis,boundary analysis and other methods were used to evaluate the interspecific differences of these five species.Nucleotide polymorphism analysis was used to discover the high-variation sites of the five species and their related species,predict the distribution of different long repeat sequences and SSRs,and then analyze the use bias of Polygonatum code.Finally,phylogenetic tree was constructed with the coding sequences of other 47 genus Polygonatum and their closely related species to explore their phylogenetic relationships in this study.Results ①Chloroplast genomes of 155 408-155 623 bp were assembled from five species of Polygonatum.A total of 132-133 genes were annotated,and 369 long repeats and 1553 simple repeats were detected.②The contraction and expansion of chloroplast genomes in 8 species were not obvious at the IRs boundary,and the size and distribution of individual genes at the LSC-IRs-SSC boundary,such as ndhF gene and ycf1 gene,were slightly different.No interspecific or intraspecific rearrangement was observed in 8 species.③ The high-variation regions of the 8 chloroplast genomes are mainly located in two single-copy regions,the duplicate copy region is relatively conserved,and the coding region is more conserved than the non-coding region.High nucleotide polymorphic loci rps16-trnQ,trnS-trnG,trnTUGU-trnL,ndhF-rpl32 and rpl32-trnL are located in the single copy region and most of them are gene spacer regions.④ The codon preference results showed that the codon preference of the five species was similar and mainly affected by selection pressure,and the third base of the codon played A dominant role and mainly ended in A/U.RSCU clustering heat map shows that PK and PZ,PCB and PS have close relationship.⑤ Phylogenetic trees divided 52 species into five branches:Ⅰ,Ⅱ,Ⅲ,ⅣandⅤ.PS,PK,PCB,PCZ and PZ were divided into ⅣandⅤbranches,among which PK and PZ were most closely related,while PCZ was more distant than the other four,was divided into the Ⅴbranch alone.Conclusion This study provided a reference for the phylogenetic research and molecular marker development of the medicinal plants of the Polygonum genus.

Objective To establish a rat model of acclimatization to motion sickness(MS)induced by rotational stimulation.Methods To determine the stimulation conditions of MS,SD rats were divided into a static control group(SCG)and a single rotation stimulation group(SRG)before being subjected to the motion sickness index(MSI)measurement,open-field experiment and Morris water maze experiment after rotational stimulation to verify the feasibility of MS being induced in rats.Morris water maze experiments were performed to find out whether rotational stimulation could be used to induce MS in rats.During experiments on acclimatization,the SD rats were divided into the control group(Ctrl),one day of rotational stimulation group(Day1),three days of continuous rotational stimulation group(Day3),and seven days of continuous rotational stimulation group(Day7)before the changes in the MSI and behavior of these rats were recorded so as to explore the relationship between continuous stimulation and MS acclimatization in rats.Results After rotational stimulation,the rats showed a significant increase in the number of fecal pellets(P<0.0001)and in the MSI(P<0.0001)compared with the SCG.In the open field experiment,the rats showed a significant decrease in the spontaneous activity time(AT)(P<0.0001),total spontaneous activity distance(TD)(P<0.001)and distance moved by the center point per second(DMCPS)(P<0.001).The time taken to climb onto the platform(latency to find the platform,LP)(P<0.0001)and the total distance to the platform(distance to the platform,DP)(P<0.001)were significantly increased during the Morris water maze experiment.Acclimatization experiments revealed a significant increase in MSI and in the number of fecal pellets in the Day1 and Day3 groups of rotational stimulation compared to the Ctrl group(P<0.0001).AT(P<0.01),TD(P<0.05)and DMCPS(P<0.01)were significantly decreased,while LP and DP were significantly increased(P<0.0001),but there was no statistically significant difference in indices compared with the Day7 group(P>0.05).Conclusion Sinusoidal stimulation can induce MS in rats,and twice-a-day,continuous rotational stimulation for seven days can lead to acclimatization.The rat MS model can be assessed via behavioral experiments.