ObjectiveTo explore the mechanism by which Qidan Yifei Tongqiao granules （QDYF） alleviate nasal mucosal remodeling in allergic rhinitis （AR） via the interleukin-33 （IL-33）/growth stimulation expressed gene 2 （ST2）/interleukin-1 receptor accessory protein （IL-1RAP） signaling pathway from the perspective of Qi-replenishing and blood-activating therapy. MethodsFirst， according to the previous network pharmacology results， this study predicted the potential mechanisms of QDYF in treating AR by screening key pathways， components， and targets. Molecular docking was performed via AutoDock and PyMOL 2.5.5. Subsequently， a rat model of ovalbumin （OVA）-induced AR was used for validation through in vivo experiments. Forty-eight rats were assigned into 6 groups： Control， model， low-dose QDYF （QDYF-L， 4.04 g·kg^-1）， medium-dose QDYF （QDYF-M， 8.08 g·kg^-1）， high-dose QDYF （QDYF-H， 16.16 g·kg^-1）， and loratadine （0.9 mg·kg^-1）. After 14 days of intervention， behavioral scores of the rats were observed. The morphological changes of nasal mucosa tissue were observed by hematoxylin-eosin （HE） staining. Masson staining was used to observe collagen fiber deposition in the nasal mucosal tissue and to calculate the collagen volume fraction （CVF）. The expression of E-cadherin （E-cad） in the nasal mucosa tissue was detected by immunofluorescence. The serum levels of helper T cell 2 （Th2） cytokines interleukin-4 （IL-4）， interleukin-5 （IL-5）， and interleukin-13 （IL-13） as well as helper T cell 1 （Th1） cytokines interleukin-2 （IL-2） and interferon-γ （INF-γ） were quantified by enzyme-linked immunosorbent assay （ELISA）. The protein levels of transforming growth factor-beta 1 （TGF-β₁）， IL-33， ST2， and IL-1RAP in the nasal mucosa tissue were determined by Western blot. ResultsIL-33， ST2， and IL-1RAP had strong binding ability with the main active ingredients—wogonin， 7-methoxy-2-methylisoflavone， formononetin， naringenin， stigmasterol， and beta-sitosterol of QDYF， with the binding energy < -4.25 kcal⋅mol^-1（1 cal≈4.184 J）. The results of in vivo experiments showed that compared with the control group， the model group exhibited increased behavioral scores （P<0.05）， aggravated pathological damage of nasal mucosa， increased collagen fiber deposition and CVF （P<0.05）， elevated serum levels of IL-4， IL-5， and IL-13， up-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）， down-regulated expression of E-cad， and declined serum levels of IL-2， IFN-γ， and IFN-γ/IL-4 ratio （P<0.05）. Compared with the model group， the QDYF groups and loratadine group showed reduced behavioral scores （P<0.05）， alleviated pathological damage of nasal mucosa， reduced collagen fiber deposition and CVF （P<0.05）， and up-regulated E-cad expression （P<0.05）. Compared with the model group， the QDYF-H group and the loratadine group showed raised levels of INF-γ and IFN-γ/IL-4 ratio （P<0.05）， declined serum levels of IL-4， IL-5， and IL-13， and down-regulated protein levels of TGF-β₁， IL-33， ST2， and IL-1RAP in the nasal mucosa （P<0.05）. In addition， the QDYF-H group exhibited an elevated serum IL-2 level （P<0.05）. The QDYF-M group showed down-regulated protein levels of TGF-β₁， IL-33 and IL-1RAP in the nasal mucosa （P<0.05）. The QDYF-L group demonstrated a down-regulated protein level of ST2 in the nasal mucosa （P<0.05）. ConclusionQDYF may regulate the Th1/Th2 balance through the IL-33/ST2/IL-1RAP signaling pathway， thereby ameliorating nasal mucosal tissue remodeling and alleviating AR.

ObjectiveTo investigate the effects and underlying mechanisms of Modified Yupingfeng Nasal Spray （玉屏风加味鼻喷剂， MYNS） on nasal mucosal tissue remodeling in allergic rhinitis （AR） model rats based on the Janus kinase 2 （JAK2）/ signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsThe chemical constituents of MYNS were identified and analyzed using liquid chromatography-tandem mass spectrometry （LC-MS/MS）. Network pharmacology and molecular docking were integrated to identify the potential targets and signaling pathways of MYNS in the treatment of AR， and to verify the crucial role of the JAK2/STAT3 pathway. Forty rats were randomly divided into blank group， model group， MYNS group， and mometasone furoate nasal spray group， with 10 rats per group. Except for the blank group， the AR rat model was established by ovalbumin （OVA） induction. After successful modeling， rats in the MYNS group received an intranasal instillation of 50 μl of MYNS at concentration of 1.05 g·ml^-¹ in each nostril， while the mometasone furoate nasal spray group received 50 μl of corresponding spray per nostril， and the model group received 50 μl of normal saline per nostril. Treatments were administered once daily. After 14 consecutive days of intervention， the frequencies of nosal scratching and sneezing in rats within 15 minutes were recorded. Hematoxylin-eosin （HE） staining was used to assess morphological changes in the nasal mucosa and perform pathological scoring. Masson staining was used to evaluate collagen fiber deposition in nasal mucosal tissue and calculate the collagen volume fraction （CVF）. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining was performed to detect apoptosis in nasal mucosal cells and record the number of apoptotic cells. Immunofluorescence assay was used to detect the expression of E-cadherin （E-Cad） in the nasal mucosa. Enzyme-linked immunosorbent assay （ELISA） was used to determine the serum levels of interleukin-4 （IL-4）， interferon-γ （IFN-γ）， histamine （HIS）， immunoglobulin E （IgE）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. Transmission electron microscopy was used to observe the ultrastructure of mitochondria in nasal mucosal epithelial cells. Flow cytometry was used to measure mitochondrial membrane potential （MMP） and reactive oxygen species （ROS） levels. Western Blot was used to determine the protein expression levels of collagen Ⅲ （Collagen Ⅲ）， α-smooth muscle actin （α-SMA）， Bcl-2-associated X protein （Bax）， Caspase-3， JAK2， phosphorylated JAK2 （p-JAK2）， STAT3， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）. ResultsA total of 626 chemical constituents were identified by LC-MS/MS. Network pharmacology screening identified 450 active ingredients. Nine intersecting components and 39 drug-AR intersecting targets were obtained. KEGG enrichment analysis indicated the involvement of signaling pathways including JAK2/STAT3. The animal experimental results showed that， compared with the blank group， rats in the model group exhibited significantly increased frequencies of nasal scratching and sneezing， as well as elevated CVF and the number of apoptotic cells， while the levels of E-Cad， MMP， and serum IFN-γ and SOD significantly decreased； meanwhile， the serum levels of IL-4， IgE， HIS， ROS， and MDA， along with the protein expression levels of Collagen Ⅲ， α-SMA， Bax， Caspase-3， p-JAK2， and p-STAT3 in the nasal mucosa， significantly increased （P＜0.05）， accompanied by aggravated pathological damage in the nasal mucosa， increased collagen fiber deposition， and abnormal mitochondrial morphology. Compared to the model group， rats in the MYNS group showed improvements in all the aforementioned indicators except for HIS （P＜0.05）， and those in the mometasone furoate nasal spray group showed improvements in all indicators except for IL-4， IgE， and SOD levels （P＜0.05）. ConclusionThe mechanism of MYNS in treating AR may be related to inhibiting the activation of the JAK2/STAT3 signaling pathway， reducing inflammatory responsesand oxidative stress， ameliorating mitochondrial damage， and suppressing nasal mucosal cell apoptosis， thereby improving nasal mucosal tissue pathological remodeling.

ObjectiveTo investigate the effects and underlying mechanisms of Modified Yupingfeng Nasal Spray （玉屏风加味鼻喷剂， MYNS） on nasal mucosal tissue remodeling in allergic rhinitis （AR） model rats based on the Janus kinase 2 （JAK2）/ signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsThe chemical constituents of MYNS were identified and analyzed using liquid chromatography-tandem mass spectrometry （LC-MS/MS）. Network pharmacology and molecular docking were integrated to identify the potential targets and signaling pathways of MYNS in the treatment of AR， and to verify the crucial role of the JAK2/STAT3 pathway. Forty rats were randomly divided into blank group， model group， MYNS group， and mometasone furoate nasal spray group， with 10 rats per group. Except for the blank group， the AR rat model was established by ovalbumin （OVA） induction. After successful modeling， rats in the MYNS group received an intranasal instillation of 50 μl of MYNS at concentration of 1.05 g·ml^-¹ in each nostril， while the mometasone furoate nasal spray group received 50 μl of corresponding spray per nostril， and the model group received 50 μl of normal saline per nostril. Treatments were administered once daily. After 14 consecutive days of intervention， the frequencies of nosal scratching and sneezing in rats within 15 minutes were recorded. Hematoxylin-eosin （HE） staining was used to assess morphological changes in the nasal mucosa and perform pathological scoring. Masson staining was used to evaluate collagen fiber deposition in nasal mucosal tissue and calculate the collagen volume fraction （CVF）. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining was performed to detect apoptosis in nasal mucosal cells and record the number of apoptotic cells. Immunofluorescence assay was used to detect the expression of E-cadherin （E-Cad） in the nasal mucosa. Enzyme-linked immunosorbent assay （ELISA） was used to determine the serum levels of interleukin-4 （IL-4）， interferon-γ （IFN-γ）， histamine （HIS）， immunoglobulin E （IgE）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. Transmission electron microscopy was used to observe the ultrastructure of mitochondria in nasal mucosal epithelial cells. Flow cytometry was used to measure mitochondrial membrane potential （MMP） and reactive oxygen species （ROS） levels. Western Blot was used to determine the protein expression levels of collagen Ⅲ （Collagen Ⅲ）， α-smooth muscle actin （α-SMA）， Bcl-2-associated X protein （Bax）， Caspase-3， JAK2， phosphorylated JAK2 （p-JAK2）， STAT3， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3）. ResultsA total of 626 chemical constituents were identified by LC-MS/MS. Network pharmacology screening identified 450 active ingredients. Nine intersecting components and 39 drug-AR intersecting targets were obtained. KEGG enrichment analysis indicated the involvement of signaling pathways including JAK2/STAT3. The animal experimental results showed that， compared with the blank group， rats in the model group exhibited significantly increased frequencies of nasal scratching and sneezing， as well as elevated CVF and the number of apoptotic cells， while the levels of E-Cad， MMP， and serum IFN-γ and SOD significantly decreased； meanwhile， the serum levels of IL-4， IgE， HIS， ROS， and MDA， along with the protein expression levels of Collagen Ⅲ， α-SMA， Bax， Caspase-3， p-JAK2， and p-STAT3 in the nasal mucosa， significantly increased （P＜0.05）， accompanied by aggravated pathological damage in the nasal mucosa， increased collagen fiber deposition， and abnormal mitochondrial morphology. Compared to the model group， rats in the MYNS group showed improvements in all the aforementioned indicators except for HIS （P＜0.05）， and those in the mometasone furoate nasal spray group showed improvements in all indicators except for IL-4， IgE， and SOD levels （P＜0.05）. ConclusionThe mechanism of MYNS in treating AR may be related to inhibiting the activation of the JAK2/STAT3 signaling pathway， reducing inflammatory responsesand oxidative stress， ameliorating mitochondrial damage， and suppressing nasal mucosal cell apoptosis， thereby improving nasal mucosal tissue pathological remodeling.

To evaluate the design and implementation effects of the "Rapid Recognition and Management of Critically Ill Patients" course, and to provide a reference for the improvement of situational simulation teaching in emergency and critical care settings.

Objective:To analyze the prevalence trend and spatiotemporal distribution characteristics of congenital heart disease in China.Methods:Data on the incidence of congenital heart disease in China and provinces from 2002 to 2021 were collected through publicly available literature and reports. Joinpoint regression was used to assess the temporal trend of the incidence of congenital heart disease. Spatial autocorrelation analysis and spatiotemporal scanning statistics were used to analyze the spatial aggregation of hotspots and clustering areas of congenital heart disease occurrence.Results:The incidence of congenital heart disease in China showed a continuously increasing trend from 2002 to 2021, with an average annual increase of 15.33% (AAPC=15.33%, P<0.001). Except for areas with missing data, 25 provinces showed an increasing trend (all AAPC>0, all P<0.05), while there was no significant change in Guangdong and Guangxi ( P=0.397 and 0.081). The results of global autocorrelation analysis showed that the occurrence of congenital heart disease had a certain clustering distribution, with the Global Moran′s I>0 in 2005, 2006 and 2016, which were 0.23, 0.26 and 0.23 ( P=0.027, 0.017 and 0.022). The results of local spatial autocorrelation showed that Hunan, Jiangxi and Fujian were high-high clustering areas, while the central and southwestern regions were low-low clustering areas. The results of segmental spatiotemporal scanning showed that eight clustering areas were found in four time periods ( P≤0.001), and the clustering areas showed a trend of gradually expanding from none to certain coverage. Conclusion:From 2002 to 2021, the overall trend of congenital heart disease in China has been on the rise, with a certain degree of spatial aggregation. The clustering areas of spatiotemporal scanning have gradually increased, and the scope has gradually expanded.

Objective:To analyze the prevalence trend and spatiotemporal distribution characteristics of congenital heart disease in China.Methods:Data on the incidence of congenital heart disease in China and provinces from 2002 to 2021 were collected through publicly available literature and reports. Joinpoint regression was used to assess the temporal trend of the incidence of congenital heart disease. Spatial autocorrelation analysis and spatiotemporal scanning statistics were used to analyze the spatial aggregation of hotspots and clustering areas of congenital heart disease occurrence.Results:The incidence of congenital heart disease in China showed a continuously increasing trend from 2002 to 2021, with an average annual increase of 15.33% (AAPC=15.33%, P<0.001). Except for areas with missing data, 25 provinces showed an increasing trend (all AAPC>0, all P<0.05), while there was no significant change in Guangdong and Guangxi ( P=0.397 and 0.081). The results of global autocorrelation analysis showed that the occurrence of congenital heart disease had a certain clustering distribution, with the Global Moran′s I>0 in 2005, 2006 and 2016, which were 0.23, 0.26 and 0.23 ( P=0.027, 0.017 and 0.022). The results of local spatial autocorrelation showed that Hunan, Jiangxi and Fujian were high-high clustering areas, while the central and southwestern regions were low-low clustering areas. The results of segmental spatiotemporal scanning showed that eight clustering areas were found in four time periods ( P≤0.001), and the clustering areas showed a trend of gradually expanding from none to certain coverage. Conclusion:From 2002 to 2021, the overall trend of congenital heart disease in China has been on the rise, with a certain degree of spatial aggregation. The clustering areas of spatiotemporal scanning have gradually increased, and the scope has gradually expanded.

One of the leading therapies for acute lymphoblastic leukemia (ALL) is the chemotherapeutic agent PEGylated E. coli-derived-l-asparaginase (PEG-ASNase). Due to the high risk of dose-limiting liver injury, characterized by clinically elevated levels of hepatic transaminases, PEG-ASNase therapy is generally avoided in adult patients. Our preclinical investigations have indicated that PEG-ASNase-induced liver injury is associated with the release of free fatty acids (FFAs) from white adipose tissue (WAT), suggesting potential lipotoxic effects. However, it remains uncertain whether PEG-ASNase directly induces hepatotoxicity or sensitizes hepatocytes to FFA-induced toxicity. Our results show that PEG-ASNase treatment results in hepatocyte apoptosis and lipid peroxidation. Ex vivo and in vitro studies in mouse and human WAT suggest that PEG-ASNase induces the expression of adipose triglyceride lipase (ATGL), activates the lipase, and stimulates adipose tissue lipolysis, suggesting that the FFAs from WAT may contribute to the observed liver injury. Moreover, treatment with PEG-ASNase sensitizes hepatocytes to FFA-induced lipotoxicity. Mechanistically, our RNA-sequencing (RNA-seq) analyses reveal that PEG-ASNase-induced sensitization to lipotoxicity is accompanied by the induction of Cyp2e1. We demonstrated that this sensitization effect is attenuated by both pharmacological and genetic inhibition of Cyp2e1. Our findings suggest that PEG-ASNase therapy induces WAT lipolysis and sensitizes hepatocytes to hepatic lipotoxicity in a Cyp2e1-dependent manner.

Objective:To explore the effects of Balint Group on the emotional stability of residents during the standardized training and the improvement of doctor-patient relationship and communication ability, so as to provide a basis for incorporating the activities of Balint Group into the daily management of the standardized training of residents and as an important course in post competency.Methods:From February to December 2021, a simple randomized controlled study was conducted at the First Affiliated Hospital of Suzhou University, 40 residents were selected and assigned to two groups. Twenty residents were enrolled in the "experimental group" to participate in the closed Balint group activities; another 20 residents did not participate in the Balint group activities and were treated as the "control group". Tools of Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Set the stage, Elicit information, Give information, Understand the patient's perspective, and End the encounter (SEGUE) were applied to evaluate the emotional state, doctor-patient relationship management, and doctor-patient communication skills of residents in the two groups in the third month, sixth month and ninth month of participating in the Balint group. SPSS 22.0 software was used for t test, and comparison among three or more groups was conducted by analysis of variance. Repeated measures data involving two factors were analyzed by repeated measures analysis of variance. Results:In the assessment of anxiety state, the scores in the experimental group decreased gradually from the sixth month to the ninth month, and there was a significant difference in the interaction effect between time and group ( F=14.57, P<0.001). In the assessment of depressive state, there was a significant difference in the interaction effect between time and group ( F=33.25, P<0.001), and the depression self-score in the experimental group decreased gradually, with an gradually increased difference between the two groups. Compared with the control group, the experimental group had significantly improvements in three dimensions of information collection, information giving, and understanding of patients. The total SEGUE score in the experimental group was improved significantly after nine months of training compared with the baseline value [(107.20±2.16) vs. (92.55±4.37), t=7.26, P<0.001]. The repeated measures analysis of variance showed that there were significant differences between the two groups in terms of information giving ( F=3.01, P=0.045) and total SEGUE score ( F=6.29, P=0.002) under the assessment of interaction between time and group. Conclusions:Balint groups can alleviate residents' anxiety and depression and play an important role in maintaining stable mood. Balint groups have an advance effect on improving residents' doctor-patient communication skills, especially in information collection, information feedback and giving, and understanding of patients.

Objective:To explore the effects of Balint Group on the emotional stability of residents during the standardized training and the improvement of doctor-patient relationship and communication ability, so as to provide a basis for incorporating the activities of Balint Group into the daily management of the standardized training of residents and as an important course in post competency.Methods:From February to December 2021, a simple randomized controlled study was conducted at the First Affiliated Hospital of Suzhou University, 40 residents were selected and assigned to two groups. Twenty residents were enrolled in the "experimental group" to participate in the closed Balint group activities; another 20 residents did not participate in the Balint group activities and were treated as the "control group". Tools of Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Set the stage, Elicit information, Give information, Understand the patient's perspective, and End the encounter (SEGUE) were applied to evaluate the emotional state, doctor-patient relationship management, and doctor-patient communication skills of residents in the two groups in the third month, sixth month and ninth month of participating in the Balint group. SPSS 22.0 software was used for t test, and comparison among three or more groups was conducted by analysis of variance. Repeated measures data involving two factors were analyzed by repeated measures analysis of variance. Results:In the assessment of anxiety state, the scores in the experimental group decreased gradually from the sixth month to the ninth month, and there was a significant difference in the interaction effect between time and group ( F=14.57, P<0.001). In the assessment of depressive state, there was a significant difference in the interaction effect between time and group ( F=33.25, P<0.001), and the depression self-score in the experimental group decreased gradually, with an gradually increased difference between the two groups. Compared with the control group, the experimental group had significantly improvements in three dimensions of information collection, information giving, and understanding of patients. The total SEGUE score in the experimental group was improved significantly after nine months of training compared with the baseline value [(107.20±2.16) vs. (92.55±4.37), t=7.26, P<0.001]. The repeated measures analysis of variance showed that there were significant differences between the two groups in terms of information giving ( F=3.01, P=0.045) and total SEGUE score ( F=6.29, P=0.002) under the assessment of interaction between time and group. Conclusions:Balint groups can alleviate residents' anxiety and depression and play an important role in maintaining stable mood. Balint groups have an advance effect on improving residents' doctor-patient communication skills, especially in information collection, information feedback and giving, and understanding of patients.

Objective To analyze medication patterns and the targets and pathways of core drug combinations in treatment of palpitation.Methods The prescriptions of Li Yaping for treatment of palpitation from March 2023 to March 2024 were collected,and frequency counts of drugs'nature and flavour,channel tropism,and efficacy were performed.Apriori algorithm,association rules,and clustering analysis were carried out using SPSS Modeler 18.0 and SPSS 26.0.The core drugs and disease targets were searched,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were performed on the targets of their therapeutic action for palpitation.Results A total of 220 prescriptions were collected,involving 192 flavors of traditional Chinese medicines,with a cumulative medication frequency of 3978 times,and 18 flavors of high-frequency medicines.The medicines were mainly tonics,sedative,and promoting blood circulation for removing blood stasis.The distribution of medicinal properties were mainly warm,cold and flat.The medicinal flavors were mainly sweet,bitter and pungent,and channel tropism were mostly heart,liver and spleen channel.Association rule analysis showed that Radix Angelicae Sinensis,Radix et Rhizoma Salviae Miltiorrhizae,Radix et Rhizoma Glycyrrhizae,Radix Ophiopogonis,and Radix Astragali were the core drugs.Cluster analysis showed that there was 3 cluster combinations.In the network pharmacology part,there were 181 targets intersected by drug combinations and diseases.KEGG analysis showed that the core drugs for palpitation mainly involved signaling pathways such as phosphoinositide 3-kinase/protein kinase B,hypoxia-inducible factor-1,mitogen-activated protein kinase,interleukin-17,etc.GO analysis obtained 1000 GO pathways,of which 760 were biological processes,93 were cellular components,and 147 were molecular functions.Conclusion In the treatment of palpitation,Li Yaping advocates benefiting qi and promoting yang,removing blood stasis and eliminating turbidity,and tranquilizing the mind,emphasizing the"two hearts in the same adjustment",and treating the heart and liver at the same time,taking into account the spleen and stomach,and the combination of core medicines can intervene in the course of palpitation through multi-components,multi-targets,and multi-pathways,which is of great significance for the treatment of palpitation in the clinical setting.