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.

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 explore the application of the first ventilatory threshold (VT1) and the second ventilatory threshold (VT2) in the classification of physical workload for plateau workers, to provide reference for formulating the classification in plateau.Methods:In August 2018, 88 male workers from substations at different altitudes (500 m, 2000 m, 3000 m and 4000 m) of a company were selected as study subjects by cluster sampling. They were divided into plain group and plateau groups.The intensities of workload were simulated by power bicycle, and physiologic parameters, including VO 2, heart rate (HR) and energy metabolic rate per body surface area (E/BSA) , were recorded in test system when reaching VT1, VT2 and peak oxygen uptake (VO 2Peak) . The ratios of VT1, VT2 and VO 2Peak to the quiet and work potential at different altitudes were compared. Results:In a quiet state, compared with the plain group, the HR and E/BSA of the workers in the 2000 m and 3000 m groups increased, and the differences were statistically significant ( P<0.05) . At VT2, compared with the plain group, the HR of the workers in the 4000 m group decreased, the difference was statistically significant ( P<0.05) . VO 2 and E/BSA of workers in each plateau group were lower than those in the plain group at VO 2Peak, and the differences were statistically significant ( P<0.05) . At VT2 and VO 2Peak, the ratios of VO 2, HR, and E/BSA relative to the quiet state of the workers in each plateau group were lower than those of the plain group, and the differences were statistically significant ( P<0.05) . In the quiet state and VT1, compared with the plain group, the remaining percentages of VO 2 and E/BSA of workers in each plateau group decreased, and the differences were statistically significant ( P<0.05) . Taking VT1, VT2 and VO 2Peak as cut-off points and VO 2, HR and E/BSA as indicators, the physical workload in plateau could be divided into four levels, namely medium, heavy, extremely heavy and extreme physical workload. Conclusion:It is practicable to use ventilatory threshold to classification of physical workload. VT1 and VT2 can be applied to the classification in plateau to supplement and optimize current national standard of physical workload.

Objective:To explore the application of the first ventilatory threshold (VT1) and the second ventilatory threshold (VT2) in the classification of physical workload for plateau workers, to provide reference for formulating the classification in plateau.Methods:In August 2018, 88 male workers from substations at different altitudes (500 m, 2000 m, 3000 m and 4000 m) of a company were selected as study subjects by cluster sampling. They were divided into plain group and plateau groups.The intensities of workload were simulated by power bicycle, and physiologic parameters, including VO 2, heart rate (HR) and energy metabolic rate per body surface area (E/BSA) , were recorded in test system when reaching VT1, VT2 and peak oxygen uptake (VO 2Peak) . The ratios of VT1, VT2 and VO 2Peak to the quiet and work potential at different altitudes were compared. Results:In a quiet state, compared with the plain group, the HR and E/BSA of the workers in the 2000 m and 3000 m groups increased, and the differences were statistically significant ( P<0.05) . At VT2, compared with the plain group, the HR of the workers in the 4000 m group decreased, the difference was statistically significant ( P<0.05) . VO 2 and E/BSA of workers in each plateau group were lower than those in the plain group at VO 2Peak, and the differences were statistically significant ( P<0.05) . At VT2 and VO 2Peak, the ratios of VO 2, HR, and E/BSA relative to the quiet state of the workers in each plateau group were lower than those of the plain group, and the differences were statistically significant ( P<0.05) . In the quiet state and VT1, compared with the plain group, the remaining percentages of VO 2 and E/BSA of workers in each plateau group decreased, and the differences were statistically significant ( P<0.05) . Taking VT1, VT2 and VO 2Peak as cut-off points and VO 2, HR and E/BSA as indicators, the physical workload in plateau could be divided into four levels, namely medium, heavy, extremely heavy and extreme physical workload. Conclusion:It is practicable to use ventilatory threshold to classification of physical workload. VT1 and VT2 can be applied to the classification in plateau to supplement and optimize current national standard of physical workload.

Objective:To evaluate the effect of edaravone on long-term cognitive function in elderly patients undergoing hip replacement.Methods:A total of 160 patients, aged≥65 yr, undergoing elective hip replacement, were divided into 2 groups ( n=80 each) using the random sequence generated by the McLeod-modified Wichmann-Hill pseudo-random number generator: edaravone group (group E) and control group (group C). Spinal-epidural anesthesia was applied in two groups.Edaravone 60 mg (in 100 ml of normal saline, infusion rate 200 ml/h) was intravenously infused from the time point immediately after achieving the anesthesia plane until the following 30 min.Serum chemokine ligand 13 (CXCL13) and interleukin-6 (IL-6) concentrations were detected by enzyme-linked immunosorbent assay before anesthesia, during surgery (30 min after skin incision), and at postoperative days 1, 3 and 7.The Confusion Assessment Method Scale in Chinese was used to detect the postoperative delirium at postoperative days 1, 2, 3 and 7, and the Telephone Interview for Cognitive Status-Modified and ADL score were adopted to assess the cognitive function and quality of daily living, respectively, and the occurrence of cognitive impairment was recorded at 1 and 12 months after surgery. Results:Compared with group C, the total Telephone Interview for Cognitive Status-Modified score and ADL score were significantly increased, the incidence of postoperative delirium and cognitive impairment was decreased, and the serum CXCL13 and IL-6 concentrations were decreased during surgery and at each time point after surgery in group E ( P<0.05). Conclusion:Edaravone can reduce inflammatory responses and improve long-term cognitive function in elderly patients undergoing hip replacement.

Objective To evaluate the correlation between the concentrations of matrix metalloproteinase-9 (MMP-9) and adiponectin (ADP) and postoperative delirium (POD) in perioperative serum of elderly patients undergoing lobectomy. Methods Seventy-three elderly patients undergoing lobectomy under general anesthesia, 38 males and 35 females, aged 65-80 years, BMI ＜ 24 kg/m2, falling into ASA physical status Ⅰ or Ⅱ, were selected in some suitable period. All patients were divided into POD group and non-POD group according to the Chinese Version of Consciousness Assessment Scale at 24 hours, 48 hours, and 72 hours after operation, and their blood samples were collected 5 minutes before induction of anesthesia (T0), at the time of tracheal extubation (T1) and at postoperative 24 hours (T2), 48 hours (T3), and 72 hours (T4) to determine the concentrations of MMP-9 and ADP in their serums. Results POD occurred in 19 patients, with the incidence rate of 17.8％. The concentrations of MMP-9 at T1-T4 were significantly higher than those before lobectomy in serums in POD group, while the concentrations of ADP in serums were significantly lower than those before lobectomy (P ＜ 0.05). The concentrations of MMP-9 in serums at T1 were significantly higher than those before lobectomy in non-POD group, while the concentrations of ADP in serums were significantly lower than those before lobectomy (P ＜ 0.05). In the comparison between the two groups, the concentrations of MMP-9 in POD group at T1-T4 were significantly higher than those in non-POD group, while the concentrations of ADP in POD group were significantly lower than those in non-POD group (P ＜ 0.05). Conclusion The serum level of MMP-9 is increased and ADP is decreased in perioperative, wich maybe involved in the pathophysiological process of POD in elderly patients undergoing lobectomy.

Objective To evaluate the relationship between perioperative peripheral blood Type 17 helper (Th17) cells and Th17-related cytokines and postoperative cognitive dysfunction (POCD) in elderly patients undergoing general anesthesia.Methods Ninety-six patients of both sexes,aged 65-86 yr,of American Society of Anesthesiologists physical status Ⅱ or m,scheduled for elective hip replacement under general anesthesia,were selected.At 3 days before operation and 1,2,3 and 7 days after operation,Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function,and fasting venous blood samples were taken for determination of the percentage of Th17 cells and serum interleukin-17 (IL-17) and IL-22 concentrations.The patients were divided into POCD group and non-POCD group according to whether the patients developed POCD at day 7 after operation or not.Pearson linear correlation of the percentage of Th17 cells and serum IL-17 and IL-22 concentrations with MoCA scores was analyzed.Results Twenty-six patients developed POCD (27.1％).The percentage of peripheral blood Th17 cells and serum IL-17 and IL-22 concentrations were significantly higher at each time point after operation than before operation in POCD group and at 1 and 2 days after operation than before operation in non-POCD group (P＜0.05).The percentage of peripheral blood Th17 cells and serum IL-17 and IL-22 concentrations were significantly higher at each time point after operation in POCD group than in non-POCD group (P＜0.05).The percentage of peripheral blood Thl7 cells was negatively correlated with MoCA scores (r =-0.867,P＜0.01) and serum IL-17 and IL-22 concentrations were negatively correlated with MoCA scores (r=-0.662 and-0.638,P＜0.01) in group POCD.Conclusion The development of POCD is related to the increase in the percentage of peripheral blood Th17 cells and concentrations of Th17-related cytokines IL-17 and IL-22 in elderly patients undergoing general anesthesia.

Objective To evaluate the effect of thoracic paravertebral block combined with general anesthesia on postoperative cognitive dysfunction (POCD) in elderly patients undergoing pulmonary lobecto-my. Methods A total of 120 elderly patients of both sexes, aged 65-81 yr, of American Society of Anes-thesiologists physical status Ⅱ or Ⅲ, with New York Heart Association Ⅰor Ⅱ, were divided into 3 groups (n＝40 each) using a random number table method: anesthesia group (group GA), epidural block combined with general anesthesia group (group EG), and paravertebral block combined with general anes-thesia group (group PG). In group PG, paravertebral block was performed under ultrasound guidance, 0. 25% ropivacaine 20 ml was injected after the paravertebral catheter was placed, and anesthesia was in-duced after confirming the plane of block. In group EG, epidural block was performed with 2% lidocaine 3 ml after epidural puncture was successfully performed at L6,7interspace, epidural 0. 375% ropivacaine 8-15 ml was intermittently injected, and anesthesia was induced after confirming the height of block. Anes- thesia was induced with IV midazolam 0. 05-0. 10 mg∕kg, etomidate 0. 3 mg∕kg, sufentanil 0. 4 μg∕kg and rocuronium 0. 6 mg∕kg. The patients were tracheally intubated and mechanically ventilated. The develop-ment of POCD was recorded at 1 day before operation and 7 days after operation. Blood samples were col-lected from the internal jugular vein before anesthesia, at 15 min after skin incision and at 7 days after oper-ation for determination of serum adiponectin ( ADP) and S-100β protein concentrations. Results Com-pared with group GA, the incidence of POCD was significantly decreased, and the serum S-100β protein concentrations were decreased and serum ADP concentrations were increased at 15 min after skin incision and 7 days after operation in PG and EG groups ( P＜0. 05). Compared with group EG, the incidence of POCD was significantly decreased, and the serum S-100β protein concentrations were increased and serum ADP concentrations were decreased at 15 min after skin incision and 7 days after operation in group PG (P＜0. 05). Conclusion Thoracic paravertebral block combined with general anesthesia induces better efficacy in decreasing the occurrence of POCD than general anesthesia alone or combination of epidural block and general anesthesia in elderly patients undergoing pulmonary lobectomy, which is related to the decreased concentrations of blood ADP in elderly patients undergoing pulmonary lobectomy.

Objective To discuss the optical coherence tomography (OCT)characteristics in patients with syphilitic chorioretinitis.Methods This was a retrospective cohort study.58 patients (88 eyes) with syphilitic chorioretinitis were included.The fluorescence fundus angiography (FFA),indocyanine green angiography (ICGA) and OCT examination were performed,and the rapid plasma regain test (RPR) and treponema pallidum particle agglutination test (TPPA) were also made.The treatment response and follow up results were analyzed.Results In this study,87 eyes represented as needle like projections of the retinal pigment epithelium,86 eyes represented as retinal external membrane and myoid,ellipsoid structure was unclear or disappear,68 eyes represented as high reflection points within the vitreous body,16 eyes represented as shallow retinal detachment.After treatment,the needle like projections of the retinal pigment epithelium were fully restored in 79 eyes,retinal external membrane and myoid,ellipsoid structure were partial displayed in 62 eyes,and shallow retinal detachment were fully restored in 16 eyes.Conclusion The manifestations of OCT in patients with syphilitic chorioretinitis include needle like projections of the retinal pigment epithelium,unclear or disappear retinal external membrane and myoid,ellipsoid structure,high reflection points within the vitreous body and shallow retinal detachment.The above manifestations of OCT can be recovered significantly with treatment.