BACKGROUND:Preliminary research by our group suggests that targeting fibroblast growth factor receptor 1(FGFR1)may be an effective strategy for treating RA. OBJECTIVE:To investigate the effects of an FGFR1 inhibitor(PD173074)on bone destruction in rats with collagen-induced arthritis. METHODS:Twenty-five female Sprague-Dawley rats were randomly divided into five groups:normal control group,model group,methotrexate group,low-dose PD173074 group,and high-dose PD173074 group.Except for the normal control group,rat models of type Ⅱ collagen-induced arthritis were made in each group.After successful modeling,rats were injected intraperitoneally with sterile PBS in the normal and model groups,1.04 mg/kg methotrexate in the methotrexate group,and 5 and 20 mg/kg in the low-dose group and high-dose PD173074 groups,once a week.After 4 weeks of drug administration,clinical symptoms and joint swelling in rats were observed.Micro-CT was used for three-dimensional reconstruction and analysis of the ankle joints.Pathological changes in the ankle joints were observed.Periarticular angiogenesis and the expression of receptor activator of nuclear factor-Κb ligand were detected.The expression levels of p-FGFR1,vascular endothelial growth factor A,and tartrate-resistant acid phosphatase in the synovial membrane were measured.Pathological changes in the liver,spleen,and kidney were observed and liver,spleen,and kidney indices were calculated. RESULTS AND CONCLUSION:PD173074 could alleviate clinical symptoms and joint swelling,delay bone loss,improve bone structure,reduce synovial invasion and cartilage bone erosion,reduce the number of periarticular osteoclasts,inhibit angiogenesis in synovial tissues,reduce the expression of receptor activator of nuclear factor-Κb ligand,and inhibit the expression of FGFR1 phosphorylated protein,tartrate-resistant acid phosphatase and vascular endothelial growth factor A.Pathologic observation of the liver,spleen and kidney in rats showed no obvious toxic side effects after PD173074 treatment.To conclude,the FGFR1 inhibitor can delay the progression of joint inflammation and bone destruction and inhibit angiogenesis in the rat model of type Ⅱ collagen-induced arthritis.The therapeutic effect of PD173074 has been preliminarily validated in the type Ⅱ collagen-induced arthritis model and may act by inhibiting FGFR1 phosphorylation,which provides a direction for the search of new therapeutic targets for rheumatoid arthritis.

BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

Objective To observe the value of AcoStream thrombus aspiration catheter for treating intermediate-high risk acute pulmonary embolism(APE).Methods Twenty-six patients with intermediate-high risk APE who underwent treatment with AcoStream thrombus aspiration catheter were retrospectively collected.The immediate technical success rate,procedure success rate and thrombus clearance rate of target vessels were recorded,as well as clinical success rate and complications in perioperative period and the recurrence of pulmonary embolism(PE)during follow-up.Results Among 26 patients with intermediate-high risk APE,the immediate technical success rate was 100%(26/26),the procedure success rate was 92.31%(24/26),and the immediate thrombus clearance rate of target vessels was 63.37%as median,including 16 cases(16/26,61.54%)achieved thrombus clearance rate grade Ⅱ or above.The perioperative period clinical success rate of treating intermediate-high risk APE was 96.15%(25/26).Two patients experienced transient arrhythmia and other 2 patients experienced worsening transient chest tightness during the procedure,and 1 case developed hematoma at the puncture site after treatment.During follow-up,no recurrence of symptomatic PE was observed.Conclusion AcoStream thrombus aspiration catheter was safe and effective for treating intermediate-high risk APE,worthy clinical promotion and application.

Objective To observe the value of AcoStream thrombus aspiration catheter for treating intermediate-high risk acute pulmonary embolism(APE).Methods Twenty-six patients with intermediate-high risk APE who underwent treatment with AcoStream thrombus aspiration catheter were retrospectively collected.The immediate technical success rate,procedure success rate and thrombus clearance rate of target vessels were recorded,as well as clinical success rate and complications in perioperative period and the recurrence of pulmonary embolism(PE)during follow-up.Results Among 26 patients with intermediate-high risk APE,the immediate technical success rate was 100%(26/26),the procedure success rate was 92.31%(24/26),and the immediate thrombus clearance rate of target vessels was 63.37%as median,including 16 cases(16/26,61.54%)achieved thrombus clearance rate grade Ⅱ or above.The perioperative period clinical success rate of treating intermediate-high risk APE was 96.15%(25/26).Two patients experienced transient arrhythmia and other 2 patients experienced worsening transient chest tightness during the procedure,and 1 case developed hematoma at the puncture site after treatment.During follow-up,no recurrence of symptomatic PE was observed.Conclusion AcoStream thrombus aspiration catheter was safe and effective for treating intermediate-high risk APE,worthy clinical promotion and application.

BACKGROUND:In clinical practice,Cibotium barometz and Epimedium have shown significant efficacy in the treatment of rheumatoid arthritis,but the complex active ingredients contained in the two have an unclear mechanism of action at the molecular level for the treatment of rheumatoid arthritis. OBJECTIVE:Based on network pharmacology and molecular docking technology,to establish a collagen-induced arthritis model and to verify the potential targets and pathways of Cibotium barometz and Epimedium in the treatment of rheumatoid arthritis,providing reliable experimental evidence for the use of clinical formulas with Cibotium barometz and Epimedium as the main components. METHODS:Utilizing traditional Chinese medicine research platforms,traditional Chinese medicine encyclopedias,and databases of traditional Chinese medicine and chemical components from the Shanghai Institute of Organic,effective ingredients were retrieved and identified.3D molecular formulas were obtained from the PubChem platform and target predictions were made using PharmMapper and SwissTargetPrediction.Disease targets for rheumatoid arthritis were obtained from gene databases such as DrugBank,GeneCards,and OMIM.The intersections of targets and Cibotium barometz and Epimedium were plotted using VENNY 2.1 after calibration with the Uniport database.A protein-protein interaction network graph was constructed using the STRING platform.Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the Metascape platform for data visualization.A four-layered network model of traditional Chinese medicine,ingredients,targets,diseases,and pathways was constructed using Cytoscape 3.9.0.The main effective ingredients were docked with core targets using AutoDock-Vina software to explore the best binding targets.A type II collagen+adjuvant-induced arthritis rat model was established,and the effects of Cibotium barometz and Epimedium on relevant pathway targets and inflammatory cell factors were observed after 21 days of intervention. RESULTS AND CONCLUSION:A total of 28 active ingredients from Cibotium barometz and Epimedium were selected,yielding 288 intersection targets for rheumatoid arthritis.The main ingredients included isobavachalcone,cibotium,and epimedium.The main targets included protein kinase 1 for serine/threonine(AKT1),tumor necrosis factor,and vascular endothelial growth factor A.Gene ontology analysis yielded 2 232 biological processes,mainly related to serine protein phosphorylation,positive regulation of serine/threonine protein kinase,and reactive oxygen metabolism.Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 202 pathways,mainly involving the PI3K/AKT signaling pathway and epidermal growth factor receptor signaling pathway,which may exert therapeutic effects by regulating synovial cell apoptosis and proliferation and suppressing inflammatory factors.Molecular docking results showed the strongest binding activity and stable structure of Cibotium barometz and Epimedium with AKT1 and estrogen receptor transcription factor 1,which was closely related to apoptosis and proliferation and inflammatory signaling pathways such as PI3K/AKT.Cibotium barometz and Epimedium reduced the expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the serum of collagen-induced arthritis rat models.Cibotium barometz and Epimedium reduced the expression of p-PI3K,p-AKT,and p-FOXO1 in the synovium of collagen-induced arthritis rat models.The results indicate that the combination of Cibotium barometz and Epimedium may exert therapeutic effects by inhibiting the proliferation of synovial cells and suppressing the expression of inflammatory factors via the PI3K/AKT/FOXO1 signaling pathway.This may be closely related to the occurrence of inflammation and bone destruction in rheumatoid arthritis,and provides a reference for the rational use and development of new drugs in clinical practice.

Objective To evaluate the performance of Xpert C. difficile multiplex real-time PCR assay for diagnosis of Clostridium difficile infections in Chinese hospital settings. Methods This study was performed in Huashan Hospital, Ruijin Hospital, Beijing Hospital, Nanfang Hospital and Sir Run Run Shaw Hospital using a standard study protocol. Unique unformed stools from patients with acute hospital-acquired diarrhea were simultaneously analyzed by toxigenic anaerobic cultures and the Xpert C. difficile assay. All specimens displaying discordant results between the Xpert assay and toxigenic culture were sent for Sanger tcdB gene sequencing. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), total concordance rate, and 95％ confidence interval (CI) were calculated before and after resolution of discordant results using SAS 9.3. Results A total of 745 stool specimens were collected and 46 were excluded due to failure of C. difficile recovery. The remaining 699 specimens were included. Compared to the results of toxigenic culture, the sensitivity, specificity, PPV, and NPV of Xpert C. difficile assay were 94.1％ (144/153)(95％CI:89.1％-97.3％), 93.2％ (509/546)(95％CI:96.7％-99.2％), 79.6％ (144/181)(95％CI:72.9％-85.2％)and 98.3％ (509 / 518) (95％CI: 96.7％-99.2％), respectively. Both methods had a Kappa of 0.819. Xpert C. difficile assay showed sensitivity of 98.4％(62/63) (95％ CI: 90.3％-99.9％) and specificity of 93.2％(509/546) (95％ CI: 90.8％-95.2％) for toxin A-negative toxin B-positive strains. After the discordant results resolved by tcdB gene sequencing, PCR assay provided better performance with high sensitivity, specificity, positive predictive value, and negative predictive value [98.8％ (171 / 173), 98.1％ (516 / 526), 94.5％ (171/181) and 99.6％ (516/518), respectively]. Conclusions Compared to the results of toxigenic culture, the sensitivity, specificity and NPV of Xpert C. difficile assay were 94.1％ (144/153) and 93.2％(509/546), respectively. With the results available within 1 h, Xpert C. difficile assay provides prompt and precise laboratory diagnosis in Chinese clinical settings.

Objective To investigate the role of spo0A gene in growth and sporulation of Clostridium difficile clinical isolates. Methods ClosTron gene knock-out system was used to knock out the spo0A gene of C. difficile strain C25. Bacterial growth curve was plotted by measuring D600 with spectrophotometer in different phases of bacterial growth. Malachite green staining technique was used to count the number of vegetative cells and spores under optical microscope. The sporulation rate was calculated. Results The spo0A mutant and its C25 parental strain showed similar patterns of growth. However, after knock-out of spo0A gene, an asporogenous phenotype was built, while the parental strain could produce spores as usual.Conclusions The spo0A gene plays a key role in sporulation but not growth of C. difficile strain.

Objective To explore a method for establishing the hamster model of Clostridium difficile-associated diarrhea (CDAD)and the indicators for its evaluation.Methods Clindamycin was administered to hamsters subcutaneously (day 1),and 24 h later infected with C.difficile clinical isolates KH1 (ribotype 027,106-108 CFU/mL)or SH9 (ribotype 001 ,108-1010 CFU/mL)by gavage.Animals were observed for CDAD symptoms such as diarrhea,weight loss and death.At the end of ob-servation period (day 7 or death),the cecum was collected from each animal for histological evaluation of inflammation.Results Following a single dose of 100 mg/kg clindamycin subcutaneously,all the animals challenged with KH1 (108 CFU/mL)devel-oped diarrhea and then died within 5 days.All the hamsters challenged with SH9 (1010 CFU/mL)developed diarrhea as well but only 66.7% died at the end of observation period.Among other groups,only one or none developed diarrhea and then died. The symptoms of hamsters with diarrhea included loose stool,wet tail and weight loss.On histological examination,conges-tion,hemorrhage and neutrophil infiltration of the mucosa were observed in the hamsters died of CDAD.Conclusions We have successfully established a hamster CDAD model that allows for future investigations.

Objective To determine the in vitro antibacterial activity of levornidazole against 375 anaerobic isolates.Methods Agar dilution method was used to determine the minimum inhibitory concentrations (MICs)of levornidazole,3 comparators (metronidazole,ornidazole and dextrornidazole)against 375 anaerobic isolates.Results For anaerobic gram-negative and gram-positive bacilli,and anaerobic gram-positive cocci,levornidazole displayed activity similar to or slightly higher than that of met-ronidazole,ornidazole and dextrornidazole.Levornidazole showed good activity against B.fragilis,Bacteroides thetaiotaomi-cron ,Clostridium difficile ,Clostridium perfringens ,and Peptostreptococcus magnus .The MIC90 value of levornidazole a-gainst the above-mentioned anaerobes was 0.5,1,0.25,2 and 1 mg/L,respectively.However,levornidazole and the compa-rators had poor antibacterial activity against Veillonella spp.among anaerobic gram-negative cocci.Conclusions The in vitro anti-anaerobic activity of levornidazole is similar to or slightly higher than that of metronidazole, ornidazole and dex-trornidazole.Levornidazole has good activity against both gram-negative and gram-positive anaerobic bacilli,and gram-positive anaerobic cocci,suggesting its promising clinical use.

Objective To evaluate the in vitro antibacterial activity of fusidic acid against P.acnes.Methods Fifty strains of P.acnes were clinically isolated from Huashan Hospital,Fudan University from March to September 2013.The minimum inhibitory concentrations (MICs) of several antibacterial agents including fusidic acid against these P.aches isolates were determined by using the agar dilution method according to the recommendations of Clinical and Laboratory Standards Institute (CLSI).Data were analyzed using the WHONET 5.4 software.Results Among the 50 P.acnes isolates,90％ were sensitive to fusidic acid,90％ to moxifloxacin,54％ to clindamycin,46％ to erythromycin,but 100％ were resistant to metronidazole.The minimum concentration required to inhibit the growth of 50％ organisms (MIC50) and 90％ organisms (MIC90) were 0.5 and 1.0 mg/L respectively for fusidic acid,whereas clindamycin and erythromycin both showed higher MIC90 values (＞ 128 mg/L).At the concentration of 128 mg/L,clindamycin inhibited the growth of 70％ of the P.acnes isolates,and erythromycin inhibited the growth of 48％ of them,while the growth of all the isolates was inhibited by fusidic acid at 2 mg/L.Conclusion Fusidic acid exhibits excellent antibacterial activity against clinical isolates of P.acnes in vitro.