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.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease. The pathogenesis of AIH remains unclear， but it is mainly autoimmune injury caused by the breakdown of autoimmune tolerance due to the abnormal activation of the immune system， while the specific molecular mechanism remains unknown. Recent studies have shown that abnormal amino acid metabolism plays an important role in the development and progression of AIH. This article reviews the research advances in amino acid metabolic reprogramming in AIH， in order to provide a theoretical basis for amino acid metabolism as a new target for the clinical diagnosis and treatment of AIH.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

ObjectiveTo observe the clinical efficacy of Shengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome. MethodA total of 90 patients suffering from carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome were randomly divided into a control group and an observation group， with 45 cases in each group. The control group was treated with polymyxin B， and the observation group was treated with Shengmaisan combined with polymyxin B. The treatment course of both groups was seven days. The infection-related indicators ［white blood cell （WBC） count， procalcitonin （PCT）， neutrophil apolipoprotein （HNL）］， inflammatory factors ［interleukin-6 （IL-6）， serum chemokine ligand 2 （CXCL2）］， and T lymphocyte subpopulations （CD3⁺， CD4⁺， CD8⁺， and CD4⁺/ CD8⁺ value）， acute physiological and chronic health Ⅱ （APACHE Ⅱ） score before and after treatment， as well as bacterial clearance rate and 28-day survival rate after treatment were observed. Result① The experiment was completed， and 81 cases were included， including 41 cases in the observation group and 40 cases in the control group. The general data of the two groups were comparable. ② The bacterial clearance rate of the observation group and the control group was 75.6% （31/41） and 52.5% （21/40）， respectively， and the observation group was higher than the control group （χ²=4.7， P<0.05）. ③ The WBC count， PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group and the control group all decreased after treatment （P<0.05）. Except for the WBC count， the PCT， HNL， IL-6， CXCL2， and APACHE Ⅱ scores of the observation group were lower than those of the control group （P<0.05）. ④ The values of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ in the observation group were increased after treatment （P<0.05）， and CD8⁺ was decreased （P<0.05）. In the control group， only CD3⁺ value was increased （P<0.05）. The values of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ in the observation group were higher than those in the control group， and the value of CD8⁺ was lower than that in the control group （P<0.05）. ⑤ The 28-day survival rate in the observation group was higher than that in the control group （χ²=4.3， P<0.05）. ConclusionShengmaisan combined with polymyxin B in the treatment of carbapenem-resistant gram-negative bacillus infection with sepsis complicated with severe acute respiratory distress syndrome can better clear bacteria， control infection， reduce the level of inflammatory factors， regulate the immune state of the body， and improve the short-term prognosis.

Objective:To investigate the impact of a pain management model based on clinical pathway (CP) refinement on postoperative pain relief, recovery, and cognitive function in patients undergoing orthopedic joint surgery.Methods:A total of 150 orthopedic joint surgery patients admitted to Handan Central Hospital from February 2018 to January 2021 were selected. They were randomly divided into an observation group (treated with a pain management model based on CP refinement) and a control group (treated with conventional pain management) using a random number table method, with 75 patients in each group. We compared the differences in pain relief, recovery, cognitive function, and postoperative complication rates between two groups of patients.Results:The Visual Analogue Scale (VAS) scores of the observation group patients at 2, 6, 12, and 24 hours after surgery were lower than those of the control group, and the differences were statistically significant (all P<0.05). 24 hours after surgery, the Japanese Orthopaedic Association (JOA) scores of both groups of patients decreased compared to before treatment, and the angle of straight leg elevation test increased compared to before treatment (all P<0.05). In addition, the JOA scores of the observation group were lower than those of the control group, and the angle of straight leg elevation test was greater than that of the control group, with statistical significance (all P<0.05). 24 hours after surgery, the Mini-mental State Examination (MMSE) scores of both groups of patients increased (all P<0.05), and the MMSE scores of the observation group were higher than those of the control group, with statistical significance (all P<0.05). The incidence of postoperative nausea and vomiting in the observation group was significantly lower than that in the control group, and the difference was statistically significant (all P<0.05). Conclusions:The analgesic model based on CP refined management has improved the postoperative analgesic effect, recovery, and cognitive function of patients undergoing orthopedic joint surgery. It is recommended to promote it clinically.

The nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome is an inflammatory protein complex, and can participate into the inflammatory response. Upon activation, these inflammasomes can lead to Caspase-1 activation, thereby inducing a cascade of inflammatory factor activation and further cell pyroptosis. Excessive activation of inflammasomes will induce the overexpression of inflammatory factors, persistently triggering immune dysregulation and inflammatory chain reactions, even causing severe damage. The recent studies have confirmed a close association between retinal diseases, such as diabetic retinopathy(DR), retinal ischemia-reperfusion injury(RIRI), and proliferative vitreoretinopathy(PVR)with immune dysregulation and inflammatory responses, which is serving as crucial factors in the progression of retinal diseases. This article reviews the NLRP3 inflammasome signaling pathway and its role in the occurrence and development of retinal diseases, in order to provide new ideas for the pathogenesis and prevention of retinal diseases.

Tumor necrosis factor-α(TNF-α)is involved in the regulation of multiple biological processes such as the proliferation,invasion,migration,and chemotherapy resistance of hepatocellular carcinoma(HCC)cells through TNF receptor-mediated signaling pathways.At the same time,TNF-α also plays a role in inducing the apoptosis of HCC cells.Some TNF-α inhibitors have been shown to inhibit the progression of HCC and prolong survival time.At present,the potential mechanism of action of TNF-α in HCC remains unclear,and exploration of the interaction between TNF-α and HCC can help to determine the potential therapeutic targets for HCC.This article summarizes the latest research advances in the mechanism of action of TNF-α in HCC and introduces the possibility of targeting TNF-α as a treatment method for HCC,in order to provide a theoretical basis for the prevention and treatment of liver cancer and drug research and development.

Objective To systematically analyze and identify key risk factors for postoperative pulmonary hemorrhage u-sing a combination of the random forest(RF)model and traditional logistic regression analysis,so as to provide data support for clinical practice.Methods This study included patients who underwent needle biopsy of lung masses from January 2020 to December 2023 in the Department of Interventional Therapy,Cancer Hospital,Tianjin Medical University.There were 844 cases,including 387 males and 457 females,ranging in age from 39 to 82 years.Clinical data and puncture-related characteristics were collected,including tumor size,puncture depth,puncture angle,presence of emphysema,lesion loca-tion in the lung,body position during puncture,whether the puncture passed through the interlobar fissure,and the number of punctures.The RF model was used to rank the importance of all variables,identifying those with the highest predictive value.Subsequently,a multivariate logistic regression model was applied to the top-ranked important variables to further e-valuate their independent impact on postoperative pulmonary hemorrhage.Results The RF model results showed that tumor size and puncture depth had the highest importance in predicting the risk of postoperative pulmonary hemorrhage.Multivari-ate logistic regression analysis further confirmed that smaller tumor size(HR:0.980,95％CI:0.971-0.989,P＜0.05)was significantly associated with a lower risk of hemorrhage,while greater puncture depth(HR:1.146,95％CI:1.063-1.235,P＜0.05)was closely related to a higher risk of hemorrhage.Additionally,other factors such as puncture angle,age,lesion location in the lung and presence of emphysema showed some influence but did not reach statistical significance in the multi-variate analysis.Conclusion This study successfully identified tumor size and puncture depth as independent risk factors for postoperative pulmonary hemorrhage by combining the RF model with multivariate logistic regression analysis.The appli-cation of the RF model improved the accuracy of feature selection,allowing us to focus on the most contributory predictive variables.These findings provide important support for preoperative risk assessment,suggesting that clinicians should priori-tize these key factors in preoperative evaluations to develop safer and more effective surgical plans,thereby reducing the risk of postoperative hemorrhage and other complications.

Objective To explore the independent risk factors that affect the overall survival(OS)of elderly patients with hepatocellular carcinoma(HCC,≥60 years old)and build a nomogram prediction model.Methods Clinical data of all elderly patients with HCC from the SEER database from 2005 to 2020 were downloaded from SEER database.In accordance with the inclusion and exclusion criteria,the screened patients were randomly assigned to a training group(70%)and a validation group(30%).The independent risk factors of elderly patients with HCC were determined by univariate and multivariate Cox regression analyses and further validated by Kaplan-Meier survival analysis.On the basis of the determined variables,nomograms were developed and verified to predict the OS of elderly patients with HCC at 6,12,and 24 months.The consistency index(C index),calibration curve,receiver's operating characteristic(ROC)curve,and area under curve(AUC)were used to evaluate the prediction efficiency and discrimination ability of the prediction model,and decision curve analysis(DCA)was used to evaluate the potential clinical application value of the nomogram.Results A total of 1134 elderly patients with HCC were included,with 793 in the training group and 341 in the validation group.Seven variables,including age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy,were identified as independent prognostic factors of this population.The constructed nomogram shows excellent prediction performance,with C indices of 0.745 in the training group and 0.704 in the validation group.The AUC values of the training group at 6,12,and 24 months were 0.785,0.788,and 0.798,respectively,and those of the validation group were 0.780,0.725,and 0.607,respectively.The calibration curve shows good consistency from the predicted survival probability to the actual probability.The ROC curve and DCA show that the nomogram proposed in this study has good prediction ability.Conclusion Age,clinical grade,clinical stage,M stage,tumor size classification,and radiotherapy are important influencing factors for the survival of elderly patients with HCC.The prediction model of prognosis nomogram constructed in this study has good predictive value,and it can be used to predict the OS of elderly patients with HCC,which could be helpful for individualized survival assessment and clinical management of these patients.