Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

OBJECTIVES: To study the effect of prophylactic phenytoin (PHT) or levetiracetam (LEV) on busulfan (BU) blood concentration in children undergoing hematopoietic stem cell transplantation. METHODS: Pediatric patients conditioned with BU plus cyclophosphamide and fludarabine at the First People's Hospital of Chenzhou from September 2023 to February 2025 were retrospectively included. Patients were grouped by prophylactic antiepileptic regimen into PHT (n=24) and LEV (n=26). BU blood concentrations at the end of infusion (0 hour) and at 1, 2, and 4 hours post-infusion were compared between groups. RESULTS: At 0 hour post-infusion, BU blood concentrations did not differ significantly between groups (P>0.05). At 1, 2, and 4 hours post-infusion, BU blood concentrations were higher in the LEV group than in the PHT group (P<0.05). The area under the concentration-time curve from 0 to ∞ (AUC_0-∞) was greater in the LEV group (P<0.001), and the attainment rate of AUC_0-∞ was higher in the LEV group than in the PHT group (73% vs 21%, P<0.001). No significant differences were observed between groups in time to hematopoietic engraftment or in the incidence of BU-related adverse drug reactions (P>0.05). CONCLUSIONS Compared with PHT, LEV prophylaxis is associated with higher BU blood concentration and a higher AUC_0-∞ attainment rate. There is no observed difference in BU efficacy or safety between PHT and LEV.
Humans ; Levetiracetam/therapeutic use* ; Busulfan/pharmacokinetics* ; Hematopoietic Stem Cell Transplantation ; Male ; Female ; Child ; Child, Preschool ; Phenytoin/pharmacology* ; Infant ; Retrospective Studies ; Anticonvulsants/pharmacology* ; Adolescent

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

The continuous accumulation of plastic waste such as polyethylene in the environment has caused serious environmental pollution issues.Considering the high similarity in the molecular structure of petroleum and polyolefin,it is feasible to apply rare earth-zeolite catalysts in polyolefin plastic upcycling,which is commonly used in fluid catalytic cracking(FCC)in the field of petroleum refining.In this study,Ce-modified HY(Ce-HY)zeolites were synthesized and characterized by a series of analytical methods,such as high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM),Fourier infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),etc.When introducing 5% Ce species into HY zeolites,the 5Ce-HY showed excellent catalytic performance in the catalytic cracking of low-density polyethylene(LDPE),which achieved 98.4% LDPE conversion with 91.5% selectivity of gaseous alkanes at 300℃,and 75.4% of them were isoparaffins.In addition,the effect of the location of rare earth species in Y zeolites on the catalytic performance was explored by fine X-ray diffraction(XRD)in the range of 11°-13°and in situ-Raman analyses.The Ce species located in the supercage of Y zeolites were more important,which enhanced the adsorption capacity and accessibility of substrate molecules,thus facilitating the entire catalytic cracking process.This method could be used to detect the location of rare earth elements in Y zeolites to understand the mechanism of rare earth catalysis.

Objective To investigate the mechanism by which artesunate(ART)attenuates intestinal mucosal barrier damage in acute graft-versus-host disease(aGVHD)and the synergistic effect of ART in combination with dexamethasone(DXM)in the treatment of aGVHD mice.Methods The aGVHD mouse model was established by bone marrow haematopoietic stem cell transplantation.The mice were divided into 9 groups,including normal mice control(Ctrl),aGVHD mice(aGVHD),normal mice receiving ART[30 mg/(kg·d)],aGVHD mice receiving low-dose ART[10 mg/(kg·d)],aGVHD mice receiving medium-dose ART[30 mg/(kg·d)],aGVHD mice receiving high-dose ART[50 mg/(kg·d)],aGVHD mice receiving DXM[20 mg/(kg·d)],aGVHD mice receiving ART[30 mg/(kg·d)]and DXM[20 mg/(kg·d)],and aGVHD mice receiving ART[30 mg/(kg·d)]and halved DXM[10 mg/(kg·d)].Survival rate and clinical parameters were assessed.HE staining and Alcian blue-periodic acid-Schiff(AB-PAS)staining were used to observe the histopathological changes in the intestinal mucosa of the mice;Real-time PCR,Western blotting and immunohistochemistry were used to detect the structure of the intestinal mucosal barrier,the T cell differentiation related transcription factors and cytokines,and the key enzymes of energy metabolism.Flow cytometry was used to detect the T helper cell 17(Th17)and regulatory T cells(Treg).Results After 30 days of ART treatment,aGVHD mice showed significant relief of systemic symptoms and increase in survival rate.In aGVHD mice treated with ART,the intestinal mucosal barrier structure was restored,and the intestinal mucosal permeability was reduced.The activity of AMP-activated protein kinase(AMPK)/mTOR pathway was inhibited,and the energy metabolism pattern of T cells was dominated by fatty acid synthesis.The balance of Th17/Treg was restored due to the decrease of Th 17 and the increase of Treg.The effect of ART+DXM treatment on aGVHD mice was comparable to that of DXM treatment alone,and the survival rate of mice was higher.In particular,the recovery of the intestinal mucosal barrier function was most obvious in the mice treated with ART+half-dose DXM.Conclusion ART reduces the immune injury of allo-T cells to the intestinal mucosal barrier by recovering the Th17/Treg balance,thus maintaining the integrity of the intestinal mucosal barrier function.The synergistic effect of ART and DXM combination treatment in aGVHD mice can reduce the incidence of DXM side effects by decreasing the dosage of DXM.

Antiviral drug research and development is an important research direction in the current and future biomedical field. The research and development of antiviral drugs not only requires the application of new strategies and new technologies, but also requires the complementary advantages and close cooperation of project teams. Based on the latest progress in this field and the author's drug research practice, this paper summarizes the underlying logic, innovative thinking and research paradigm of antiviral medicinal chemistry.

This study was aimed at understanding the serotypes,virulence,drug resistance,and genetics of the pathogenic genes from 29 strains of foodborne Listeria monocytogenes in Guizhou Province in 2022.The minimum inhibitory concentration(MIC)values against eight antibiotics were determined with the microbroth dilution method,and whole genome sequencing was performed on 29 L.monocytogenes strains isolated from food microbiology and foodborne disease surveillance efforts in the province in 2022.The genome sequences were assembled,and bioinformatics analyses were conducted to examine genealogy,serogroups,sequence analysis(ST type),clonal groups(CC type),resistance genes,and virulence genes.A total of 29 strains of L.monocytogenes had resistance to zero to eight antibiotics,and carried six resistance genes.All strains of L.monocytogenes carried fosX,mprF,Lin,and norB.The 29 strains of L.monocytogenes belonged to 2 lineages(Ⅰ and Ⅱ):17 strains belonged to lineage Ⅱ,which was the dominant strain,and 12 strains belonged to lineage Ⅰ.The strains were classified into 13 ST types,among which ST8 was dominant,accounting for 31.03％(9/29 strains),and was followed by ST619 and ST121,accounting for three strains each.The strains were di-vided into four serogroups,with 15 strains in serogroups 1/2a and 3a;11 strains in serogroups 1/2b,3b,and 7;2 strains in serogroups 1/2c and 3c;and 1 strain in serogroups 4b,4d,and 4e.The strains were divided into 12 CC types,and one unsub-divided CC type,ST2348,among which CC8 was dominant,accounting for 27.59％(nine strains).A total of 25 virulence genes were found,which belonged to three virulence islands(LIPI-1,LIPI-2,and LIPI-3)and 23 CL types,including one or two strains each,and three CL types including two strains each.Foodborne L.monocytogenes in Guizhou Province has a low level of drug resistance,carries a high number of virulence genes,and shows genetic diversity in serogroups and molecular phe-notypes.These findings should strengthen the continuous surveillance efforts for Listeria monocytogenes.

This study was aimed at studying the phenotypic and molecular characteristics of a Salmonella Grumpensis isolate from a patient with diarrhea in Shanghai,to provide evi-dence for the prevention of salmonellosis.Biochemical identifi-cation,serum agglutination testing,antimicrobial susceptibility testing,and whole genome sequencing(WGS)were performed on isolate 2023JD76.Global Salmonella Grumpensis genome sequences were searched and downloaded for serotyping predic-tion,multilocus sequence typing(MLST),prediction of anti-microbia resistance genes and virulence genes,and phylogenetic analysis of 2023JD76.The 2023JD76 strain was identified as Salmonella Grumpensis(13,23:d:1,7)with ST2060,and was susceptible to 20 antimicrobial agents.Strain 2023JD76 carried the aminoglycoside resistance gene aac(6')-Iaa and five types of virulence genes:the adhesion genes csg and rat;the secretion and transport genes sip and inv;the typhoid toxin genes cdt and plt;the invasive gene nutrient metabolism factor mgt;and the antimicrobial peptide resistance factor mig.Global S.Grumpensis strains harbored ten types of antimicrobial resistance genes whose prevalence ranged from 58.33％to 100％.The global genome sequences of S.Grumpensis were divided into two lineages.Lineage I was dominated by ST751(88.89％,16/18),and lineage Ⅱ was dominated by ST2060(89.47％,17/19).The genome sequence of strain 2023JD76 belonged to lineage Ⅱ,and was closely related to the genome sequences from human fecal and human cerebrospinal fluid.This study provides the first report of a S.Grumpensis isolate from the stool of a patient with diarrhea in China.Considerable variability in antimicrobial resistance genes was observed among genome sequences from different sources,and the strains harbored a substantial number of virulence genes.Enhanced surveillance should be emphasized to prevent a potential risk of global dissemination.

Aim To investigate the effects of berberine(BBR)combined with 5'-n-ethylformamidoadenosine(NECA)on myocardial H9c2 and HL-1 cell damage induced by hypoxia/reoxygenation(H/R).Methods H9c2 and HL-1 cells were divided into the Control group,BBR group,NECA group,combined administra-tion group,H/R group,BBR+H/R group,NECA+H/R group,and combined administration+H/R group.CCK-8 was used to detect cell viability in each group.The TMRE kit was used to detect MMP.DCFH-DA was used to detect ROS content.The Mito SOX Red fluorescent probe was used to detect mitochondrial su-peroxide.The expressions of COX Ⅳ,Tom20,and Tim23 were detected by Western blot.The expression of COX Ⅳ and Tom20 genes was detected by qRT-PCR.Results In H9c2 cells,the cell viability and TMRE fluorescence intensity in the H/R group were significantly decreased compared with the Control group.The protein expressions of COX Ⅳ,Tom20,and Tim23,gene expressions of COX Ⅳ and Tom20,ROS,and mitochondrial superoxide contents were significant-ly increased.Compared with the H/R group,the cell viability of BBR and NECA were enhanced after ad-ministration alone.The contents of ROS and mitochon-drial superoxide were significantly decreased.In HL-1 cells,cell viability in the H/R group was significantly decreased compared with the Control group.The con-tents of ROS and mitochondrial superoxide were signifi-cantly increased.Compared with the H/R group,BBR and NECA alone and combined administration en-hanced cell viability.The contents of ROS and mito-chondrial superoxide were significantly decreased.Conclusion The administration of BBR and NECA a-lone or in combination can reduce the production of mi-tochondrial superoxide and cell ROS,thereby allevia-ting mitochondrial damage,alleviating oxidative stress damage,and ultimately reducing H/R-induced myocar-dial cell damage.