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.

ObjectiveTo explore the mechanism by which modified Shaofu Zhuyutang inhibits angiogenesis in endometriosis via the vascular endothelial growth factor （VEGF）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/endothelial nitric oxide synthase （eNOS）-nitric oxide （NO） signaling pathway. MethodsEighty-four female SD rats were randomly assigned into blank， sham operation， model， positive control （gestrinone， 0.25 mg·kg^-1）， high-， medium-， and low-dose （30， 15， 7.5 g·kg^-1， respectively） traditional Chinese medicine （TCM， modified Shaofu Zhuyutang） groups. A rat model of endometriosis was established by the autotransplantation method. After successful modeling， rats in the drug intervention groups were administrated with corresponding agents by gavage， and those in the blank， sham operation， and model groups received an equal volume of distilled water. After 28 days of gavage， rats were administrated with oxytocin， and the number and latency period of writhing responses were observed. Serum samples from each group， ectopic lesions from modeling groups， and uteri from blank and sham operation groups were collected. Hematoxylin-eosin staining was used to observe the pathological morphology of endometriotic lesions. Immunohistochemistry was employed to observe the expression of angiogenesis-specific markers cluster of differentiation 34 antigen （CD34） and friend leukemia virus integration-1 （FLI-1）. Enzyme-linked immunosorbent assay and the nitrate reductase method were employed to determine the serum levels of VEGF and NO， respectively. Western blot was employed to measure the protein levels of VEGF， PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， eNOS， and phosphorylated eNOS （p-eNOS）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to determine the mRNA levels of VEGF， PI3K， Akt， and eNOS. ResultsThe blank group and the sham operation group had no significant changes in the number and latency period of writhing responses， serum VEGF and NO levels， protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and mRNA levels of VEGF， PI3K， Akt， and eNOS. The model group showed an increase in the number and a reduction in the latency period of writhing responses， enlargement of ectopic endometrial tissue in the abdominal wall， with stromal hyperplasia， glandular dilation， and increased vasculature. In addition， the modeling led to increased positive expression of CD34 and FLI-1， elevated serum VEGF and NO levels， and up-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS （P<0.01）. Compared with the model group， the gestrinone and high-， medium-， and low-dose TCM groups showed a significant reduction in the number of writhing responses， a significant prolongation of the latency period， reduced ectopic endometrial tissue in the abdominal wall， alleviated pathological damage， and reduced positive expression of CD34 and FLI-1. The gestrinone group and the high- and medium-dose TCM groups showed lowered serum VEGF and NO levels as well as down-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS. Moreover， the low-dose TCM group showed reductions in the serum VEGF level， the protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and the mRNA levels of VEGF and eNOS （P<0.05， P<0.01）. ConclusionModified SShaofu Zhuyutang can inhibit angiogenesis in endometriosis by antagonizing the abnormal activation of the VEGF/PI3K/Akt/eNOS-NO signaling pathway， thereby preventing the occurrence， development， and deterioration of endometriosis.

ObjectiveTo explore the mechanism by which modified Shaofu Zhuyutang inhibits angiogenesis in endometriosis via the vascular endothelial growth factor （VEGF）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/endothelial nitric oxide synthase （eNOS）-nitric oxide （NO） signaling pathway. MethodsEighty-four female SD rats were randomly assigned into blank， sham operation， model， positive control （gestrinone， 0.25 mg·kg^-1）， high-， medium-， and low-dose （30， 15， 7.5 g·kg^-1， respectively） traditional Chinese medicine （TCM， modified Shaofu Zhuyutang） groups. A rat model of endometriosis was established by the autotransplantation method. After successful modeling， rats in the drug intervention groups were administrated with corresponding agents by gavage， and those in the blank， sham operation， and model groups received an equal volume of distilled water. After 28 days of gavage， rats were administrated with oxytocin， and the number and latency period of writhing responses were observed. Serum samples from each group， ectopic lesions from modeling groups， and uteri from blank and sham operation groups were collected. Hematoxylin-eosin staining was used to observe the pathological morphology of endometriotic lesions. Immunohistochemistry was employed to observe the expression of angiogenesis-specific markers cluster of differentiation 34 antigen （CD34） and friend leukemia virus integration-1 （FLI-1）. Enzyme-linked immunosorbent assay and the nitrate reductase method were employed to determine the serum levels of VEGF and NO， respectively. Western blot was employed to measure the protein levels of VEGF， PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， eNOS， and phosphorylated eNOS （p-eNOS）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to determine the mRNA levels of VEGF， PI3K， Akt， and eNOS. ResultsThe blank group and the sham operation group had no significant changes in the number and latency period of writhing responses， serum VEGF and NO levels， protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and mRNA levels of VEGF， PI3K， Akt， and eNOS. The model group showed an increase in the number and a reduction in the latency period of writhing responses， enlargement of ectopic endometrial tissue in the abdominal wall， with stromal hyperplasia， glandular dilation， and increased vasculature. In addition， the modeling led to increased positive expression of CD34 and FLI-1， elevated serum VEGF and NO levels， and up-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS （P<0.01）. Compared with the model group， the gestrinone and high-， medium-， and low-dose TCM groups showed a significant reduction in the number of writhing responses， a significant prolongation of the latency period， reduced ectopic endometrial tissue in the abdominal wall， alleviated pathological damage， and reduced positive expression of CD34 and FLI-1. The gestrinone group and the high- and medium-dose TCM groups showed lowered serum VEGF and NO levels as well as down-regulated protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS and mRNA levels of VEGF， PI3K， Akt， and eNOS. Moreover， the low-dose TCM group showed reductions in the serum VEGF level， the protein levels of VEGF， p-PI3K/PI3K， p-Akt/Akt， and p-eNOS/eNOS， and the mRNA levels of VEGF and eNOS （P<0.05， P<0.01）. ConclusionModified SShaofu Zhuyutang can inhibit angiogenesis in endometriosis by antagonizing the abnormal activation of the VEGF/PI3K/Akt/eNOS-NO signaling pathway， thereby preventing the occurrence， development， and deterioration of endometriosis.

ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Cardiovascular diseases （CVD），a group of common diseases in clinical practice，are witnessing a steady rise in both incidence and mortality rates，posing a challenge to public health. Gualou Xiebai Banxiatang，originating from Synopsis of the Golden Chamber （《金匮要略》），was initially used to treat severe cases of chest impediment. The formula consists of Trichosanthis Fructus，Allii Macrostemonis Bulbus，Pinelliae Rhizoma，and Baijiu. It has a wide range of clinical applications，with therapeutic effects including moving Qi to relieve depression，activating Yang to dissipate mass，and expelling phlegm to alleviate chest congestion. In recent years，clinical research has confirmed that Gualou Xiebai Banxiatang，with or without modification，used alone or in combination with Western medicine，has definite effects in the treatment of CVD such as hyperlipidemia，coronary atherosclerotic heart disease，hypertension，heart failure，and arrhythmia. It can alleviate disease symptoms and reduce the risk of re-hospitalization. Basic research indicates that the mechanisms of Gualou Xiebai Banxiatang include improving endothelial functions，exhibiting anti-inflammatory properties，countering oxidative stress，preventing apoptosis，inhibiting ventricular remodeling，regulating mitochondrial functions，improving hemorheology，and modulating autophagy and neurotransmitters. This article reviews relevant articles in recent years with focuses on the compatibility，clinical application，and mechanism of Gualou Xiebai Banxiatang. This review is expected to provide a theoretical basis for the mechanism research and clinical application of this formula in treating CVD and to offer ideas and reference for in-depth research.

Eight compounds were isolated and purified from the ethyl acetate part of 70% acetone extract of Rehmannia glutinosa by various chromatographic techniques such as silica gel, MCI gel CHP-20, ODS, Toyopearl HW-40C, combined with TLC and semi-preparative HPLC. Their structures were elucidated by modern spectroscopy techniques (NMR, MS, UV, IR), and identified as neomartynoside A (1), osmanthuside B₆ (2), martynoside (3), isomartynoside (4), (E)-p-hydroxycinnamic acid (5), caffeic acid (6), ferulic acid (7), and methyl caffeate (8). Compound 1 is a new phenylethanol glycoside, which was identified as neomartynoside A. Compound 2 was isolated from Rehmannia glutinosa for the first time. In addition, compounds 2, 6 and 7 significantly increased relative glucose consumption, showing potential hypoglycemic activity.

Objective: To explore the impact of household tobacco smoke exposure on adolescents attempted smoking behavior, so as to provide a reference for tobacco control policy formulation and evaluation. Methods: From September to November 2023, a stratified cluster random sampling method was employed to select 7 841 middle and high school students from 10 monitoring sites (districts/counties) in Beijing for a questionnaire survey. Rao-Scott Chi square test was used to assess differences in proportions across subgroups, and complex sampling design based multivariate Logistic regression analysis was conducted to explore the influence of parental smoking and secondhand smoke (SHS) exposure at home on adolescents attempted smoking behavior. Results: About 47.17% of adolescents reported to have at least one parent smoked, with 42.36% reported of having only the father smoked, 0.73% reported of having only the mother smoked, and 4.08% reported of having both parents smoked. About 34.66% of middle and high school students were reported SHS exposure at home in the past 7 days, with 10.98%, 4.79% and 18.89% reported SHS exposure for 1-2, 3-4 and 5-7 days. Compared to adolescents with non smoking parents, those with a smoking father or both smoking parents had higher rates of attempted smoking [ OR (95% CI )=1.45(1.06-1.98), 3.73(2.18-6.37), P < 0.05 ]. Compared to adolescents without SHS exposure at home in the past 7 days, those exposed for 3-4 or 5- 7 days had higher rates of attempted smoking [ OR (95% CI )=2.21(1.27- 3.84 ), 2.46(1.58-3.83), P <0.01]. Conclusions Household tobacco smoke exposure is associated with adolescent attempted smoking behavior. Parents should quit smoking and prohibit smoking at home to create a smoke free environment for adolescents.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.