Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

Chronic obstructive pulmonary disease （COPD）， as one of the three major causes of death， is a complex systemic disease with high prevalence， high mortality， high disability， frequent acute exacerbations， and a variety of pulmonary complications. The pathogenesis is complex. Western medicine has no effective specificity scheme for a complete cure. However， multiple-component and multiple-target characteristics of traditional Chinese medicine （TCM） demonstrate significant advantages in COPD treatment through multi-link， multi-pathway， and multi-mechanism intervention. Therefore， exploring the essence of COPD pathogenesis and discovering effective TCM treatment drugs through the application of TCM principles and prescriptions is a key focus of modern research. Animal models are of paramount importance in medical research. It is the first consideration to select appropriate animals， adopt reasonable modeling methods to replicate stable animal models that closely resemble the clinical manifestations and pathophysiological characteristics of COPD， and use appropriate evaluation methods to determine the success of COPD animal models in experimental research. The core of experimental research lies in observing the intervention effect of TCM on COPD animal models， exploring the specific pathways and regulatory mechanisms of TCM on COPD disease， and finding TCM monomers， single herbs， and TCM formulas with definite curative effects. At present， animal model research on COPD mainly involves model establishment， model evaluation， efficacy observation， mechanism exploration， and other aspects. In recent years， there has been no systematic organization， update， and reflection on the relevant research on TCM intervention in COPD animal models. This study reviewed the selection of animals for the COPD model， methods for establishing COPD animal models， model evaluation methods， and the intervention effects of TCM on COPD animal models. It aims to grasp the current research status and identify existing problems for further improvement， in order to provide evidence and support for scientific research and clinical treatment of COPD.

BACKGROUND:In the skeleton,various endogenous or exogenous stimuli cause imbalance in bone metabolism,leading to changes in bone mass and bone strength,which in turn cause a series of bone-related diseases such as osteoarthritis and osteoporosis.In this process,Forkhead box transcription factor O1(FoxO1)plays an important role,and FoxO1 can regulate bone metabolism by regulating oxidative stress,cell proliferation,differentiation and apoptosis. OBJECTIVE:This paper focuses on FoxO1,and by summarizing its upstream and downstream regulatory mechanisms,it provides new ideas for the future treatment of bone-related diseases. METHODS:The search terms"FoxO1,Bone"were used for literature retrieval in CNKI and WanFang Databases,and the search terms"FoxO1,Bone,Skeleton"were used in PubMed and Web of Science databases.The old,repetitive,poor quality and irrelevant papers were excluded,and 56 papers were finally included for review and analysis. RESULTS AND CONCLUSION:(1)FoxO1 promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts by increasing the expression of runt-related transcription factor 2,alkaline phosphatase and osteocalcin,and transforms bone marrow mesenchymal stem cells from lipogenic differentiation to osteogenic differentiation by inhibiting peroxisome proliferator-activated receptor γ,thereby increasing bone formation.In addition,FoxO1 may also affect bone formation by increasing the number of osteoblasts.(2)Inhibition of FoxO1 in bone marrow mononuclear macrophages can reduce the expression of macrophage colony-stimulating factor,receptor activator of nuclear factor-κB ligand and nuclear factor of activated T cells 1,promote the expression of FoxO1 in osteoclasts,and thus inhibit osteoclast differentiation.In addition,direct activation of FoxO1 also inhibits osteoclast differentiation and weakens osteoclast activity.(3)Upregulation of FoxO1 in chondrocytes can regulate chondrocyte homeostasis,protect chondrocytes from oxidative stress,and promote the expression of autophagy related genes and the secretion of proteoglycan 4 by chondrocytes.(4)This paper details the molecular mechanism of FoxO1 regulation in different bone cells in detail,and elaborates the key role of FoxO1 in the treatment of bone-related diseases more comprehensive and deeply,providing new ideas for the treatment of osteoarthritis,osteoporosis,delayed fracture healing and other bone-related diseases.

ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis （IPF）. MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation （30 patients） and control groups （30 patients）. All patients underwent standard Western medical therapy. Additionally，the observation group received Shenlong decoction granules，while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each，taken twice daily for three months. The indexes of the patients during the treatment cycle were observed，and the main indexes include traditional Chinese medicine （TCM） syndrome scores and 6 min walk test （6MWT）. The secondary indexes include pulmonary function test ［actual value/expected value of total lung volume （TLC%），actual value/expected value of vital capacity（FVC%），actual/predicted diffusing capacity of the lung for carbon monoxide（DLCO%），actual/predicted forced expiratory volume in one second （FEV₁%），and FEV₁/ forced vital capacity （FVC）］，blood gas analysis ［arterial blood diathesis partial pressure of oxygen （PaO₂），partial pressure of carbon dioxide （PaCO₂），and arterial oxygen saturation （SaO₂）］，serum inflammatory factors ［transforming growth factor-β₁ （TGF-β₁），interleukin-4 （IL-4），interleukin-13 （IL-13），interleukin-12 （IL-12），and gamma-interferon （IFN-γ）］，and quality of survival evaluation ［St George's Respiratory Questionnaire （SGRQ） score］. The patients' clinical manifestations were determined at the end of the treatment， and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study，comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period，the control group achieved a total effective rate of 33.33% （9/27），whereas the observation group demonstrated a total effective rate of 53.85% （14/26），which was statistically superior to the control group （χ²=4.034，P<0.05）. After the treatment，the TCM syndrome scores，6MWT，DLCO%，FEV₁%，PaO₂，PaCO₂，TGF-β₁，IL-4，IL-13，IL-12，and IFN-γ in the two groups were all significantly improved （P<0.01）. Compared with those in the control group after treatment at the same period，the TCM syndrome scores，6MWT，PaO₂，and PaCO₂ were significantly improved in the observation group after 60 days and 90 days of medication （P<0.01）. Three months after the end of medication，the SGRQ score in the observation group showed significant improvement when compared to that in the control group （P<0.05），and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF，enhance exercise tolerance，improve the quality of life，and have certain potential advantages in improving pulmonary function.

ObjectiveTo assess the therapeutic effectiveness and safety of the traditional Chinese medicine compound Shenlong decoction in addressing the symptoms of pulmonary deficiency and stasis in patients with idiopathic pulmonary fibrosis （IPF）. MethodsSixty eligible patients with lung deficiency and collateral stasis syndrome of IPF were randomly assigned to the observation （30 patients） and control groups （30 patients）. All patients underwent standard Western medical therapy. Additionally，the observation group received Shenlong decoction granules，while the control group received a placebo. Both treatments were packaged in four doses of 10.5 g each，taken twice daily for three months. The indexes of the patients during the treatment cycle were observed，and the main indexes include traditional Chinese medicine （TCM） syndrome scores and 6 min walk test （6MWT）. The secondary indexes include pulmonary function test ［actual value/expected value of total lung volume （TLC%），actual value/expected value of vital capacity（FVC%），actual/predicted diffusing capacity of the lung for carbon monoxide（DLCO%），actual/predicted forced expiratory volume in one second （FEV₁%），and FEV₁/ forced vital capacity （FVC）］，blood gas analysis ［arterial blood diathesis partial pressure of oxygen （PaO₂），partial pressure of carbon dioxide （PaCO₂），and arterial oxygen saturation （SaO₂）］，serum inflammatory factors ［transforming growth factor-β₁ （TGF-β₁），interleukin-4 （IL-4），interleukin-13 （IL-13），interleukin-12 （IL-12），and gamma-interferon （IFN-γ）］，and quality of survival evaluation ［St George's Respiratory Questionnaire （SGRQ） score］. The patients' clinical manifestations were determined at the end of the treatment， and the occurrence of adverse events was recorded. ResultsA total of 53 patients completed the study，comprising 27 in the control group and 26 in the observation group. Upon completion of the treatment period，the control group achieved a total effective rate of 33.33% （9/27），whereas the observation group demonstrated a total effective rate of 53.85% （14/26），which was statistically superior to the control group （χ²=4.034，P<0.05）. After the treatment，the TCM syndrome scores，6MWT，DLCO%，FEV₁%，PaO₂，PaCO₂，TGF-β₁，IL-4，IL-13，IL-12，and IFN-γ in the two groups were all significantly improved （P<0.01）. Compared with those in the control group after treatment at the same period，the TCM syndrome scores，6MWT，PaO₂，and PaCO₂ were significantly improved in the observation group after 60 days and 90 days of medication （P<0.01）. Three months after the end of medication，the SGRQ score in the observation group showed significant improvement when compared to that in the control group （P<0.05），and no severe adverse events were reported during the follow-up period. ConclusionCompound Shenlong decoction can alleviate clinical symptoms such as shortness of breath and wheezing in patients with lung deficiency and collateral stasis syndrome of IPF，enhance exercise tolerance，improve the quality of life，and have certain potential advantages in improving pulmonary function.

ObjectiveTo clarify the neuroprotective effect of black Panacis Quinquefolii Radix（PQR） and explore its active ingredients， with the aim of establishing an activity-oriented quality evaluation method. MethodsTransgenic Tg（HuC∶EGFP） zebrafish was used to establish a neuronal injury model by aluminum chloride immersion. Different doses（10， 20 mg·L^-1） of PQR and black PQR ethanol extracts were administered. The neuroprotective effects of PQR and black PQR were compared by analyzing the fluorescent area and intensity of zebrafish neurons. Based on ultra-performance liquid chromatography（UPLC）， a fingerprint profile of black PQR was established， followed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential components were screened using the criteria of variable importance in the projection（VIP） value>1 and P<0.05. The neuroprotective activity of 14 batches of black PQR was assessed， and Spearman correlation analysis was used to identify saponins related to neuroprotective activity， which were then validated. Based on the above results， active marker components were determined， and an UPLC method was established for their quantitation with clear content limits. ResultsPharmacological efficacy results showed that both PQR and black PQR at different doses could significantly improved neuronal damage in zebrafish. At a dose of 20 mg·L^-1， black PQR demonstrated superior efficacy（P<0.05）. The fingerprint similarities of 14 batches of black PQR were>0.94， with 26 common peaks identified. Through comparison with the reference standards， 8 components were confirmed， including peak 1（ginsenoside Rg₁）， peak 2（ginsenoside Re）， peak 5（ginsenoside Rb₁）， peak 9（ginsenoside Rd）， peak 16［ginsenoside 20（S）-Rg₃］， peak 17［ginsenoside 20（R）-Rg₃］， peak 18（ginsenoside Rk₁）， and peak 19（ginsenoside Rg₅）. The results of PCA and OPLS-DA indicated that there were differences in saponins among black PQR samples from different origins， and 12 differential components were screened. All 14 batches of black PQR exhibited good protective effects on zebrafish neurons， with Shaanxi-produced black PQR showing superior protective effects compared to the other three production regions. Spearman correlation analysis revealed that a total of 11 components， including ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅， showed a significant positive correlation with the neuroprotective effect in zebrafish（P<0.05）. The activity validation results indicated that ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅ were the primary components responsible for the neuroprotective effects of black PQR. Quantitative analysis showed that the content of ginsenoside 20（S）-Rg₃ in 14 batches of black PQR ranged from 0.17% to 0.52%， and the repair rate of neuronal damage ranged from 42.77% to 97.83%. ConclusionBased on the fingerprint and neuronal protective activity， the spectrum-effect related quality control model of black PQR was established， with ginsenoside 20（S）-Rg₃ as the quality control index， and the neuronal damage repair rate≥60% as the evaluation standard， the minimum limit of ginsenoside 20（S）-Rg₃ in black PQR should be≥0.20%.

ObjectiveTo assess the quality consistency of black Panacis Quinquefolii Radix（bPQR） decoction pieces prepared by atmospheric and pressurized steaming processes based on chromaticity-chemical composition-vasoactive inhibition. The ultimate goal was to screen the pressurized steaming process yielding quality equivalent to atmospheric steaming， and optimize the processing technology of bPQR. MethodsThe bPQR decoction pieces were prepared using both atmospheric and pressurized steaming processes， and the chromaticity values［lightness value（L^*）， red/green chromaticity value（a^*）， yellow/blue chromaticity value（b^*）， total chromaticity value（E^*ab）］ were measured. High performance liquid chromatography（HPLC） was employed to establish fingerprint profiles for the decoction pieces， and cluster analysis was conducted on chromaticity values and the common peak areas in fingerprint profiles to elucidate the quality relationships between the decoction pieces processed by different methods. The optimal atmospheric steaming of bPQR decoction pieces was determined through zebrafish angiogenesis inhibition experiments. The contents of ginsenosides Rg₁， Re， Rb₁， 20（S）-Rg₃， Rk₁ and Rg₅ in the decoction pieces were quantified， and Spearman correlation analysis was employed to investigate the relationship between saponin content， chromaticity， and angiogenesis inhibition activity during the steaming process. By integrating the consistency of chromaticity， saponin components and angiogenesis inhibition activity， pressurized steaming conditions with quality equivalent to the atmospheric pressure method were selected. ResultsCompared with the atmospheric steaming method， pressurized steaming resulted in faster color darkening and higher conversion rates of ginsenosides in bPQR decoction pieces. Moreover， the neovascularization inhibitory activity of bPQR decoction pieces continued to increase with the deepening of processing. Based on the effectiveness and safety， the optimal process for preparing bPQR decoction pieces with neovascularization inhibitory activity was determined to be atmospheric steaming for 21 h. All six ginsenosides tested exhibited strong to extremely strong correlations with both the chromaticity values of the decoction pieces and their neovascularization inhibitory activities. Among them， ginsenosides Rg₁， Re and Rb₁ exhibited positive correlations with chromaticity values and negative correlations with zebrafish angiogenesis inhibition activity. Conversely， ginsenosides 20（S）-Rg₃， Rk₁ and Rg₅ showed negative correlations with chromaticity values and positive correlations with zebrafish angiogenesis inhibition activity. By integrating chromaticity values， cluster analysis results， as well as the results of activity， it was determined that the quality of bPQR decoction pieces steamed under pressurized conditions of 110 ℃（0.045 MPa） for 5 h and 115 ℃（0.07 MPa） for 3 h was highly consistent with that obtained by atmospheric steaming for 21 h. ConclusionThe preparation of bPQR decoction pieces by pressurized steaming has the advantages of short preparation time， low energy consumption， and rapid saponin conversion rate， making it a viable alternative to atmospheric steaming for preparing bPQR decoction pieces. Meanwhile， the evaluation method based on chromaticity-chemical composition-activity can provide a more scientific and effective explanation of change rules in the quality during traditional Chinese medicine processing， and offer a new model for optimizing processing technology and enhancing quality control.

Objective To explore the value of blood inflammatory load in predicting overall survival of elderly patients with epithelial ovarian cancer(EOC).Methods Elderly patients with EOC were selected,and their clinical data and peripheral blood parameters were collected.We constructed an inflammation-related blood scoring system using univariate and multivariate Cox regression analysis.The Kaplan-Meier method was used for survival analysis.We used Cox proportional hazards analysis to identify the independent prognostic factors.A nomogram model was constructed based on independent prognostic factors,and the receiver operating characteristic curve,C-index,and calibration curve were used to evaluate the model.Results Patients with high blood inflammatory load had worse prognosis(P=0.002).Compared with the low inflammatory load group,patients with high inflammatory load had later clinical stages and larger ascites volume(P<0.05).Cox regression analysis showed that ACCI,CA125,residual lesions,and blood score were independent factors affecting overall survival(P<0.05).Conclusion The blood inflammatory load is the biomarker for the prognosis of elderly patients with EOC.Scoring the inflammatory load in the blood can assist in efficacy monitoring and treatment intervention of ovarian cancer patients.

Objective:To develop and evaluate the efficacy and safety of a three-dimensional (3D) digestive endoscope for gastric endoscopic submucosal dissection (ESD) through animal experiments.Methods:Two Dutch pigs were utilized from the Zhengzhou University Animal Experiment Center for the study. ESD procedures were performed by two senior endoscopists, one using 3D glasses and the other utilizing a 3D high-definition head display. The success of ESD was assessed based on predefined criteria, including completion of surgical steps, complete detachment of the presumptive lesion, and effective bleeding control during and after the surgery. The number of successful procedures and incidences of perforation were recorded. The stereoscopic experience of the endoscopists, including both the primary endoscopist and the assistant, was also evaluated. Furthermore, the assessment encompassed any reported symptoms of eye discomfort, such as eye fatigue, ocular pain, and blurred vision. Additionally, the confidence level of the endoscopists in the mechanical aspects of the operation, as well as encountered issues during the endoscopic procedures, were documented.Results:Two ESD were successful and no perforation occurred. Feedback from endoscopists suggested that 3D digestive endoscopy offered clear images with enhanced three-dimensionality during surgery, clear sense of distance and layering, allowing for a precise judgment of bleeding points, which surpassed 2D capabilities. No eye discomfort was experienced by endoscopists or assistants during or after the procedures. While endoscopists exhibited high confidence in 3D digestive endoscopy, they noted issues with image blurring when the camera was positioned less than 10 mm from the gastrointestinal tract wall.Conclusion:Preliminary results show that 3D digestive endoscopes can provide excellent stereo imaging, improved positioning accuracy, and safety during live animal stomach ESD procedures, without significantly increasing endoscopists' eye discomfort. Nevertheless, efforts are needed to address image blurring concerns when the camera is close to the gastrointestinal tract wall.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.