ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.

Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Objective:To investigate the effects of lipids and lipopolysaccharide (LPS) in Artemisia pollen on the induction of allergic rhinitis in a murine model. Methods:BALB/c mice were randomly divided into seven groups using the random number table method as follows: defatted pollen group (TZ group, n=5), defatted pollen+ LPS group (TZLPS group, n=5), non-defatted pollen group (WTZ group, n=5), non-defatted pollen+ LPS group (WTZLPS group, n=5), PBS group ( n=5), PBS+ LPS group (PBSLPS group, n=5), and blank control group ( n=6). On days 1, 8, and 15, the mice in the TZ and TZLPS groups received a subcutaneous injection in the neck region with 0.1 ml of defatted Artemisia pollen extract (20 μg/ml); the WTZ and WTZLPS groups were administered 0.1 ml of non-defatted Artemisia pollen extract (20 μg/ml), while the PBS and PBSLPS groups were injected with 0.1 ml of PBS (0.1 mol/L). From days 22 to 28, the mice were subjected to intranasal challenge to induce allergic rhinitis symptoms. The TZ, WTZ, and PBS groups received nasal administration of 10 μl per nostril of defatted Artemisia pollen extract (500 μg/ml), non-defatted Artemisia pollen extract (500 μg/ml), and PBS (0.1 mol/L), respectively. For the TZLPS, WTZLPS, and PBSLPS groups, an additional 260 EU (5.2 μl) of LPS was co-administered per nostril alongside the corresponding base solutions. The blank control group received no intervention during this phase. The behaviors of the mice were observed; the levels of specific IgE, IgG1 and IgG2a in serum samples were detected by ELISA; the pathological changes in nasal mucosa and lung tissues were observed by HE staining, and the expression of both IL-4 and IL-5 was observed by immunohistochemistry. One-way analysis of variance and Kruskal-Wallis test were used for statistical analysis. Results:Following Artemisia pollen antigen challenge, the total TZ group (TZLPS group+ TZ group) exhibited significantly higher behavioral scores as compared with the total PBS group (PBSLPS group+ PBS group) and the blank control group (both P<0.001). Serum analysis revealed that the total TZ group showed markedly elevated levels of Artemisia-specific IgE compared with the total WTZ group (WTZLPS group+ WTZ group) and the total PBS group ( P<0.05, P<0.001), along with significantly higher IgG1 levels than the total PBS and blank control groups ( P<0.05, P<0.001), while no significant differences in IgG2a levels were observed among these groups (all P>0.05). In local inflammatory responses, eosinophil infiltration and IL-4/IL-5 expression in both nasal mucosa and lung tissues of mice in the total TZ group were significantly higher than those in the total PBS and blank control groups (all P<0.001). Notably, eosinophil counts in nasal mucosa of mice in the total TZ group surpassed those in the total WTZ group ( P<0.05), whereas no significant differences in IL-4/IL-5 expression in mouse nasal mucosa were detected between the total TZ and total WTZ groups (both P>0.05). LPS supplementation in pollen extracts showed no significant effects on the specific IgE, IgG1, or IgG2a levels in serum across groups (all P>0.05), nor did it alter eosinophil activation or IL-4 expression in mouse nasal mucosa (all P>0.05). However, compared with the TZ group, eosinophil counts and IL-4 expression in lung tissues of mice in the TZLPS group were significantly increased (both P<0.001). Conclusions:This study successfully establishes a mouse model of Artemisia pollen allergy, and finds that the defatting treatment of Artemisia pollen can induce more intense inflammatory response. The presence or absence of LPS in pollen has no significant effect on allergic inflammation in the nasal mucosa, but it can cause different degrees of damage to the lung tissues of mice.

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.

Objective:To explore the experience of emotion management and program needs of patients with vasovagal syncope (VVS) from the doctor-nurse-patient perspective.Methods:This study was a phenomenological study in qualitative research. Using purposive sampling method, four medical specialists, four nursing specialists, and 10 patients with VVS from the Syncope Center of Shanghai East Hospital, Tongji University were selected from March to May 2024 for semi-structured interviews. Colaizzi's phenomenological data analysis was used to analyze the data.Results:Theme 1 was the initial perception and experience of emotion management, in which the doctor-nurse perspective included two sub-themes of emotion management met the actual needs of clinical patients and the management program was too specialized and unknown, and the patient perspective included three sub-themes of differences in the ability of individuals to recognize their own emotional state, lack of knowledge related to emotion management, and lack of social support. Theme 2 was the need for emotion management programs, in which the doctor-nurse perspective involved two sub-themes of multidisciplinary cooperation, suitable for clinical operation and follow-up, and the combination of online and offline, and in-hospital and out-of-hospital linkage, and the patient perspective involved two sub-themes of the need for healthcare guidance, easy to operate, and the diversification of forms, personalization, and meeting the needs of different populations.Conclusions:The content of emotion management is relatively unknown to doctors, nurses and patients, and even more so to patients. VVS emotion management work is still in its infancy, and emotion management as a branch of rehabilitation needs to be emphasized for its development, and psychological assessment and intervention work should be incorporated into the routine of syncope rehabilitation.

Pollen allergen-induced allergic rhinitis(AR),also known as seasonal allergic rhinitis(SAR),typically manifests during the period of pollen dissemination by anemophilous plants.The prevalence of SAR has more than doubled over the past three decades.The etiology of SAR is multifaceted,involving factors such as pollen allergens,environmental and climatic conditions,genetic predispositions,and the immunological status of the individual.Animal models provide a critical tool for elucidating the mechanisms underlying AR and advancing the development of effective preventive and therapeutic strategies.This review synthesizes the recent pertinent domestic and international literature on pollen-sensitized AR animal experiments.It systematically delineates the factors influencing the efficacy of these models,including the selection of animal strains,the production and associated challenges of sensitizing agents,specifically pollen antigens,the utilization and limitations of adjuvants,the procedural steps involved in model creation,and the method ologies for evaluating model effectiveness.The insights provided are intended to offer guidance and support for the development of appropriate animal models of pollen-induced AR,thereby facilitating both fundamental and applied research in this area.

Pollen allergen-induced allergic rhinitis(AR),also known as seasonal allergic rhinitis(SAR),typically manifests during the period of pollen dissemination by anemophilous plants.The prevalence of SAR has more than doubled over the past three decades.The etiology of SAR is multifaceted,involving factors such as pollen allergens,environmental and climatic conditions,genetic predispositions,and the immunological status of the individual.Animal models provide a critical tool for elucidating the mechanisms underlying AR and advancing the development of effective preventive and therapeutic strategies.This review synthesizes the recent pertinent domestic and international literature on pollen-sensitized AR animal experiments.It systematically delineates the factors influencing the efficacy of these models,including the selection of animal strains,the production and associated challenges of sensitizing agents,specifically pollen antigens,the utilization and limitations of adjuvants,the procedural steps involved in model creation,and the method ologies for evaluating model effectiveness.The insights provided are intended to offer guidance and support for the development of appropriate animal models of pollen-induced AR,thereby facilitating both fundamental and applied research in this area.

Objective:To explore the experience of emotion management and program needs of patients with vasovagal syncope (VVS) from the doctor-nurse-patient perspective.Methods:This study was a phenomenological study in qualitative research. Using purposive sampling method, four medical specialists, four nursing specialists, and 10 patients with VVS from the Syncope Center of Shanghai East Hospital, Tongji University were selected from March to May 2024 for semi-structured interviews. Colaizzi's phenomenological data analysis was used to analyze the data.Results:Theme 1 was the initial perception and experience of emotion management, in which the doctor-nurse perspective included two sub-themes of emotion management met the actual needs of clinical patients and the management program was too specialized and unknown, and the patient perspective included three sub-themes of differences in the ability of individuals to recognize their own emotional state, lack of knowledge related to emotion management, and lack of social support. Theme 2 was the need for emotion management programs, in which the doctor-nurse perspective involved two sub-themes of multidisciplinary cooperation, suitable for clinical operation and follow-up, and the combination of online and offline, and in-hospital and out-of-hospital linkage, and the patient perspective involved two sub-themes of the need for healthcare guidance, easy to operate, and the diversification of forms, personalization, and meeting the needs of different populations.Conclusions:The content of emotion management is relatively unknown to doctors, nurses and patients, and even more so to patients. VVS emotion management work is still in its infancy, and emotion management as a branch of rehabilitation needs to be emphasized for its development, and psychological assessment and intervention work should be incorporated into the routine of syncope rehabilitation.

Objective:To investigate the effects of lipids and lipopolysaccharide (LPS) in Artemisia pollen on the induction of allergic rhinitis in a murine model. Methods:BALB/c mice were randomly divided into seven groups using the random number table method as follows: defatted pollen group (TZ group, n=5), defatted pollen+ LPS group (TZLPS group, n=5), non-defatted pollen group (WTZ group, n=5), non-defatted pollen+ LPS group (WTZLPS group, n=5), PBS group ( n=5), PBS+ LPS group (PBSLPS group, n=5), and blank control group ( n=6). On days 1, 8, and 15, the mice in the TZ and TZLPS groups received a subcutaneous injection in the neck region with 0.1 ml of defatted Artemisia pollen extract (20 μg/ml); the WTZ and WTZLPS groups were administered 0.1 ml of non-defatted Artemisia pollen extract (20 μg/ml), while the PBS and PBSLPS groups were injected with 0.1 ml of PBS (0.1 mol/L). From days 22 to 28, the mice were subjected to intranasal challenge to induce allergic rhinitis symptoms. The TZ, WTZ, and PBS groups received nasal administration of 10 μl per nostril of defatted Artemisia pollen extract (500 μg/ml), non-defatted Artemisia pollen extract (500 μg/ml), and PBS (0.1 mol/L), respectively. For the TZLPS, WTZLPS, and PBSLPS groups, an additional 260 EU (5.2 μl) of LPS was co-administered per nostril alongside the corresponding base solutions. The blank control group received no intervention during this phase. The behaviors of the mice were observed; the levels of specific IgE, IgG1 and IgG2a in serum samples were detected by ELISA; the pathological changes in nasal mucosa and lung tissues were observed by HE staining, and the expression of both IL-4 and IL-5 was observed by immunohistochemistry. One-way analysis of variance and Kruskal-Wallis test were used for statistical analysis. Results:Following Artemisia pollen antigen challenge, the total TZ group (TZLPS group+ TZ group) exhibited significantly higher behavioral scores as compared with the total PBS group (PBSLPS group+ PBS group) and the blank control group (both P<0.001). Serum analysis revealed that the total TZ group showed markedly elevated levels of Artemisia-specific IgE compared with the total WTZ group (WTZLPS group+ WTZ group) and the total PBS group ( P<0.05, P<0.001), along with significantly higher IgG1 levels than the total PBS and blank control groups ( P<0.05, P<0.001), while no significant differences in IgG2a levels were observed among these groups (all P>0.05). In local inflammatory responses, eosinophil infiltration and IL-4/IL-5 expression in both nasal mucosa and lung tissues of mice in the total TZ group were significantly higher than those in the total PBS and blank control groups (all P<0.001). Notably, eosinophil counts in nasal mucosa of mice in the total TZ group surpassed those in the total WTZ group ( P<0.05), whereas no significant differences in IL-4/IL-5 expression in mouse nasal mucosa were detected between the total TZ and total WTZ groups (both P>0.05). LPS supplementation in pollen extracts showed no significant effects on the specific IgE, IgG1, or IgG2a levels in serum across groups (all P>0.05), nor did it alter eosinophil activation or IL-4 expression in mouse nasal mucosa (all P>0.05). However, compared with the TZ group, eosinophil counts and IL-4 expression in lung tissues of mice in the TZLPS group were significantly increased (both P<0.001). Conclusions:This study successfully establishes a mouse model of Artemisia pollen allergy, and finds that the defatting treatment of Artemisia pollen can induce more intense inflammatory response. The presence or absence of LPS in pollen has no significant effect on allergic inflammation in the nasal mucosa, but it can cause different degrees of damage to the lung tissues of mice.

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.