Objective To establish,evaluate and validate the Nomogram prediction model of radiation pneumonitis(RP)in intensity modulated radiotherapy(IMRT)with TCM syndrome elements.Methods 257 patients with locally advanved non-small cell lung cancer receiving IMRT were analyzed retrospectively.The total population was randomly divided into a training set and a validation set by 7:3.A prediction model was established by Lasso-Logistic regression analysis,and then visualized by Nomogram to evaluate and validate the model.Results Independent risk factors included in the prediction model included tumor stage(OR=6.576;P=0.003),position(OR=2.935;P=0.016),MLD of the affected lung(OR=1.001;P<0.001)and Yin deficiency(OR=3.861;P=0.003).Based on the above factors,the prediction model was constructed and visualized.The C-index of the training set and the validation set were 0.865 and 0.867,respectively.The calibration curves of the two sets had a good fit and had certain clinical usefulness.Conclusion Based on the clinical elements of Chinese and Western medicine,tumor stage,position,lung MLD and Yin deficiency,the model can accurately predict the occurrence of≥grade 2 RP,and provide a reference for clinical screening of high-risk patients and further improvement of treatment plan.

Objective To develop an animal model that replicates the clinical phenotype of severe asthma.Methods Ovalbumin(OVA)combined with IL-33 or varying doses of lipopolysaccharides(LPS)was used to explore the construction of a severe asthma mouse model.Established model animals were assessed for lung function,number of inflammatory cells,and lung tissue pathology were assessed.Expression of key genes associated with severe asthma identified from the GEO database were validated in the new model.Results Compared with OVA alone,OVA combined with IL-33 or 5 μg LPS significantly increased airway resistance and the number of inflammatory cells in bronchoalveolar lavage fluid,and aggravated the pathological damage to lung tissues.The expression patterns of key genes in the newly constructed severe asthma models were consistent with those observed in clinical patients with severe asthma.Conclusions The modeling method of combining OVA with IL-33 or LPS(5 μg)can be used to construct experimentalanimal models of severe asthma.

Objective To explore the mechanism of Bufei Jiedu Granules in the treatment of methicillin-resistant Staphylococcus aureus(MRSA)chronic infection using network pharmacology;To verify it through animal experiments.Methods Active components and potential targets in Bufei Jiedu Granules were screened through the TCMSP database,and genes related to MRSA infection were retrieved through GeneCards,OMIM,DisGeNET,TTD,DrugBank and PharmGKB databases.The STRING database was employed to construct a protein-protein interaction network on common targets,and GO and KEGG pathway enrichment analysis were conducted to identify key signaling pathways for Bufei Jiedu Granules treatment of MRSA infection.The effects of Bufei Jiedu Granules on bacterial load and pathological changes in the lung,liver and kidney of MRSA chronic infection mice models were evaluated through WT and T/B immune cell deficient Rag2-/-mouse animal experiments.The mRNA expressions of inflammatory factors(IFN-γ,IL-10)and immune checkpoints(PD1,TIM3)were detected.Results Totally 54 active components related to Bufei Jiedu Granules were selected,and 50 potential targets related to MRSA infection were identified.118 signaling pathways significantly associated with MRSA infection were identified through GO and KEGG pathway enrichment analysis,in which the JAK-STAT signaling pathway,Th17 cell differentiation,and PD-L1 expression and PD-1 checkpoint pathway were closely related to cell activation and T cell differentiation.Animal experimental results indicated that Bufei Jiedu Granules could effectively reduce the bacterial load in organs and ameliorate the pathological damage in the chronic MRSA infection mouse model,increase the mRNA expression of IFN-γ in the lung tissue,and decrease the mRNA expressions of IL-10,PD1 and TIM3.Conclusion Bufei Jiedu Granules has the characteristics of multi-component and multi-target in the treatment of MRSA infection,and may be involved in adaptive immune activation to effectively treat chronic MRSA infection.

Objective To establish,evaluate and validate the Nomogram prediction model of radiation pneumonitis(RP)in intensity modulated radiotherapy(IMRT)with TCM syndrome elements.Methods 257 patients with locally advanved non-small cell lung cancer receiving IMRT were analyzed retrospectively.The total population was randomly divided into a training set and a validation set by 7:3.A prediction model was established by Lasso-Logistic regression analysis,and then visualized by Nomogram to evaluate and validate the model.Results Independent risk factors included in the prediction model included tumor stage(OR=6.576;P=0.003),position(OR=2.935;P=0.016),MLD of the affected lung(OR=1.001;P<0.001)and Yin deficiency(OR=3.861;P=0.003).Based on the above factors,the prediction model was constructed and visualized.The C-index of the training set and the validation set were 0.865 and 0.867,respectively.The calibration curves of the two sets had a good fit and had certain clinical usefulness.Conclusion Based on the clinical elements of Chinese and Western medicine,tumor stage,position,lung MLD and Yin deficiency,the model can accurately predict the occurrence of≥grade 2 RP,and provide a reference for clinical screening of high-risk patients and further improvement of treatment plan.

Objective To develop an animal model that replicates the clinical phenotype of severe asthma.Methods Ovalbumin(OVA)combined with IL-33 or varying doses of lipopolysaccharides(LPS)was used to explore the construction of a severe asthma mouse model.Established model animals were assessed for lung function,number of inflammatory cells,and lung tissue pathology were assessed.Expression of key genes associated with severe asthma identified from the GEO database were validated in the new model.Results Compared with OVA alone,OVA combined with IL-33 or 5 μg LPS significantly increased airway resistance and the number of inflammatory cells in bronchoalveolar lavage fluid,and aggravated the pathological damage to lung tissues.The expression patterns of key genes in the newly constructed severe asthma models were consistent with those observed in clinical patients with severe asthma.Conclusions The modeling method of combining OVA with IL-33 or LPS(5 μg)can be used to construct experimentalanimal models of severe asthma.

Objective To explore the mechanism of Bufei Jiedu Granules in the treatment of methicillin-resistant Staphylococcus aureus(MRSA)chronic infection using network pharmacology;To verify it through animal experiments.Methods Active components and potential targets in Bufei Jiedu Granules were screened through the TCMSP database,and genes related to MRSA infection were retrieved through GeneCards,OMIM,DisGeNET,TTD,DrugBank and PharmGKB databases.The STRING database was employed to construct a protein-protein interaction network on common targets,and GO and KEGG pathway enrichment analysis were conducted to identify key signaling pathways for Bufei Jiedu Granules treatment of MRSA infection.The effects of Bufei Jiedu Granules on bacterial load and pathological changes in the lung,liver and kidney of MRSA chronic infection mice models were evaluated through WT and T/B immune cell deficient Rag2-/-mouse animal experiments.The mRNA expressions of inflammatory factors(IFN-γ,IL-10)and immune checkpoints(PD1,TIM3)were detected.Results Totally 54 active components related to Bufei Jiedu Granules were selected,and 50 potential targets related to MRSA infection were identified.118 signaling pathways significantly associated with MRSA infection were identified through GO and KEGG pathway enrichment analysis,in which the JAK-STAT signaling pathway,Th17 cell differentiation,and PD-L1 expression and PD-1 checkpoint pathway were closely related to cell activation and T cell differentiation.Animal experimental results indicated that Bufei Jiedu Granules could effectively reduce the bacterial load in organs and ameliorate the pathological damage in the chronic MRSA infection mouse model,increase the mRNA expression of IFN-γ in the lung tissue,and decrease the mRNA expressions of IL-10,PD1 and TIM3.Conclusion Bufei Jiedu Granules has the characteristics of multi-component and multi-target in the treatment of MRSA infection,and may be involved in adaptive immune activation to effectively treat chronic MRSA infection.

Objective:To explore and validate the targets of Salvia miltiorrhiza in myopia using network pharmacology and molecular docking technology. Methods:The TCMSP database was used to extract the targets of Salvia miltiorrhiza.GeneCards, DisGeNET, Malacard and OMIM databases were used to extract the myopia-related targets.The target intersection was taken, and the intersecting targets were selected to extract the corresponding active ingredients of traditional Chinese medicine (TCM) and construct the pharmacological regulatory network of TCM using Cytoscape.The protein interaction network map for the key target genes was constructed using the String database, and the relevant proteins were selected to download the three-dimensional structures of the active ingredients from the PubChem database, and molecular docking was performed using AutoDockvina software.Twelve 3-week-old guinea pigs were induced with lens-induced myopia (LIM) in the right eye and randomly divided into normal saline group and sodium danshensu group, with 6 animals in each group.During the maintenance of LIM, periocular injection of 1 ml normal saline or sodium danshensu was performed daily.The contralateral eye was used as a negative control.On days 0, 14, and 28 of the experiment, the axial length of both eyes was measured by A-scan ultrasonography, and the refractive status was assessed with a streak retinoscope.To avoid individual differences, relative spherical equivalent (treated eye-contralateral eye) and relative axial length (treated eye-contralateral eye) were compared.On day 28, the relative expression levels of hypoxia-inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1) proteins were determined by Western blot.The feeding and use of laboratory animals followed the 3R principle, and the research program was approved by the Ethics Committee of Experimental Animal Center of Zhengzhou University (No.ZZU-LAC 202320405[02]). Results:Sixteen intersecting key targets were screened for myopia and TCM components derived from Salvia divinorum.A TCM network pharmacology map and protein interaction map were constructed with Salvia divinorum as a drug candidate, and the corresponding proteins of target genes, such as MMP2, TGFB1, and MMP9 were screened to perform molecular docking with the active ingredients, such as lignocellulosic acid, danshensu, tanshinone ⅡA, and so on.After 14 days of induction, the relative spherical equivalent and relative axial length were (-4.67±1.03)D and (0.67±0.26)mm in sodium danshensu group, and (-6.30±1.22)D and (1.08±0.34)mm normal saline group, indicating slower myopia progression and axial elongation in sodium danshensu group, and the differences were statistically significant ( t=2.412, P=0.039; t=2.750, P=0.049). The relative expression levels of HIF-1α protein were 0.20±0.01, 1.29±0.05 and 0.63±0.02, and the relative expression levels of TGF-β1 protein were 0.93±0.05, 0.25±0.01 and 0.74±0.05 in the negative control, normal saline and sodium danshensu groups, respectively.The expression of HIF-1α protein was higher in sodium danshensu group than in negative control group but lower than in the normal saline group, and the expression of TGF-β1 protein was lower in sodium danshensu group than in negative control group but higher than in the normal saline group, showing statistically significant differences (all at P<0.05). Conclusions:Natural compounds extracted from Salvia divinorum extracts may serve as potential drug candidates to combat scleral hypoxia and improve scleral extracellular matrix remodeling.

Objectives:To evaluate the tricuspid valve(TV)geometric remodeling in patients with idiopathic pulmonary arterial hypertension(IPAH)by three-dimensional transthoracic echocardiography. Methods:Two-dimensional and three-dimensional transthoracic echocardiography were performed in 30 IPAH patients and 15 healthy controls,and the geometry parameters of TV were obtained by four-dimensional auto tricuspid valve quantitative(4D Auto-TVQ)in the right ventricular-focused apical view.Pulmonary arterial hypertension was determined by right heart catheterization within 48 hours of echocardiography. Results:The 4-chamber diameter,tricuspid annular(TA)perimeter,TA area,maximal tenting height,coaptation point height and tenting volume were larger in IPAH patients than those in healthy controls(all P＜0.05),2-chamber diameter was similar between two groups.In IPAH group,maximal tenting height and coaptation point height were moderately correlated with right ventricular end-diastolic volume(r=0.710,r=0.515,both P＜0.05),while TA perimeter,4-chamber diameter and TA area were moderately correlated with right atrial end-systolic volume(r=0.712,r=0.558,r=0.545,all P＜0.05). Conclusions:IPAH patients have larger maximal tenting height,coaptation point height and tenting volume,TA enlargement is mainly visible in 4-chamber diameter.TV tenting height is associated with right ventricular volume,but TA size is associated with right atrial volume in IPAH patients.

Objective To explore the mechanism of Baihu Decoction in the treatment of acute lung injury based on network pharmacology and molecular docking technology;To carry out experimental verification.Methods The active components and targets of Baihu Decoction were searched through TCMSP and BATMAN-TCM databases,and human gene searches were conducted in GeneCards,NCBI,and OMIM databases.PPI network construction and GO and KEGG pathway enrichment analysis were conducted to determine the important signaling pathways of Baihu Decoction and acute lung injury.Molecular docking of main active components and core target proteins was performed.The effects of Baihu Decoction on survival rate and inflammatory cytokine content in acute lung injury lethal model mice were observed through animal experiments.Results Totally 211 common targets for Baihu Decoction and acute lung injury were screened,and identified effective components such as quercetin,kaempferol,and stigmasterol,etc.Analysis of KEGG pathway enrichment indicated that Baihu Decoction exerted its pharmacological effects in acute lung injury through a variety of signal pathways,including Toll-like receptor signaling pathway,NOD-like receptor signaling pathway,T cell receptor signaling pathway,and MAPK signaling pathway.Molecular docking results showed that Baihu Decoction had good binding strength with MAPK14,STAT3,JUN,MAPK1,MAPK3,FOS and RELA.The results of animal experiments showed that compared with the model group,the survival rate of mice in the Baihu Decoction group was significantly increased,the degree of pathological injury in the lung tissue was reduced,and serum IL-6,TNF-α contents decreased significantly(P<0.05).Conclusion Baihu Decoction can treat acute lung injury by reducing pathological injury to lung tissue and releasing of inflammatory factors.

Objective To understand the awareness rate and willingness of parents of school-age infants and young children in Huangpu District, Shanghai to receive the 13 valent pneumococcal conjugate vaccine (PCV13) and its influencing factors, and to provide basic data for formulating community health education policies. Methods A stratified random sampling method was used to conduct a full coverage questionnaire survey on the PVC13 awareness rate and vaccination willingness of 1030 parents of infants and young children in 10 communities. Results A total of 1000 questionnaire surveys were completed, with an accurate response rate of 97.08%. The awareness rate of PCV13 was 85.50%, and the awareness rate of complications was less than 80%. The PCV13 vaccination rate was 55.60%. 38.74% of the reasons for not being vaccinated were concerned about vaccine side effects, and 32.21% were concerned about vaccine quality. The higher the education level of parents and the per capita annual income of the family, the higher the awareness rate of pneumococcal vaccine knowledge and the willingness to receive vaccination. Parents with registered residence in other places had low willingness to vaccinate PCV13. Conclusion The public has a higher awareness of PCV13 and a higher willingness to receive vaccination. It is necessary to strengthen the scientific popularization of complications of pneumococcal pneumonia and vaccine safety, strengthen vaccine safety supervision and disclosure of regulatory results, and strengthen PCV13 science popularization for parents of infants and young children with registered residence outside the city.