OBJECTIVE To study the ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury （ALI） based on serum exosomal microRNA （miRNA）. METHODS The rats were randomly divided into a blank group （normal saline）， model group （nomal saline）， and F. suspensa-L. japonica herb pair group （2.55 g/kg）， with 10 rats in each group. Except for the blank group， the other groups were used to establish an ALI model by intratracheal dripping of 5 mg/ mL lipopolysaccharides. After modeling， each group was given relevant medicine/normal saline intragastrically， once a day， for 3 consecutive days. After the last medication， the pathological status of lung tissue was observed； lung wet-to-dry weight ratio and leukocyte counts in bronchoalveolar lavage fluid （BALF） were determined. The levels of inflammatory factors [tumor necrosis factor-α（TNF-α）， interleukin-1β （IL-1β）， IL-10] in BALF were determined. Exosomes were isolated from rat serum， and high- throughput sequencing technology was employed to screen differentially expressed miRNA within the exosomes， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Based on the screened differentially expressed miRNA and the enriched KEGG pathways， in vitro cellular experiments were conducted for validation. RESULTS The animal experimental results demonstrated that after intervention with the F. suspensa-L. japonica herb pair， the wet-to-dry weight ratio， the number of leukocytes in BALF， as well as the levels of TNF-α and IL-1β in BALF of ALI rats were all significantly reduced （P＜0.01）， while the level of IL-10 was significantly increased （P＜0.01）. The results of high-throughput sequencing experiments revealed that the F. suspensa-L. japonica herb pair could significantly up-regulate the expressions of miR-345-3p， miR-194-5p， miR-653-5p， and others in exosomes. Among them， the KEGG pathways involved in the target genes of differentially expressed miRNA included the hypoxia-inducible factor-1（HIF-1） signaling pathway， among others. The results of cellular E-mail：huang.haiying@126.com validation experiments showed that overexpressed miR-345-3p could significantly elevate the level of IL-10 in the cell supernatant （P＜0.01）， while significantly reducing the levels of TNF-α and IL-1β in the cell supernatant， as well as the mRNA and protein expression levels of protein kinase B1， phosphatidylinositol 3- kinase， and HIF-1α （P＜0.01）. CONCLUSIONS F. suspensa-L. japonica herb pair can alleviate inflammatory responses and thereby exert a therapeutic effect in improving ALI by up-regulating the expression of miR-345-3p in serum exosomes and inhibiting the activity of the HIF-1 signaling pathway.

ObjectiveTo investigate the mechanism of Forsythiae Fructus-Lonicerae Japonicae Flos（FF） in the treatment of acute lung injury（ALI） by investigating the effects of FF on serum metabolomics of rats with ALI. MethodsThirty male SD rats were acclimated for 1 week， and 6 rats were randomly selected as the blank group. The other 24 rats were injected with lipopolysaccharide（LPS） solution by tracheal drip to establish an ALI model. After successful model establishment， the rats were randomly divided into the model group， the FF low-dose group（3.0 g·kg^-1）， the FF high-dose group（6.0 g·kg^-1）， and the dexamethasone group（5 mg·kg^-1）， with six rats in each group. The FF low- and high-dose groups and the dexamethasone group were received daily oral administration of the corresponding drug solution， and the blank group and the model group were gavaged with an equal amount of saline， treatment was administered continuously for 3 d. The pathological conditions of rat lung tissues were evaluated by hematoxylin-eosin（HE） staining， wet/dry mass ratio（W/D） of the lung tissues， and protein concentration in rat bronchoalveolar lavage fluid（BALF）. Metabolomic analysis of rat serum was performed by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， combined with multivariate statistical analysis， the potential biomarkers of FF in treating ALI were screened by variable importance in the projection（VIP） value>1， P<0.05 from t-test， and log₂fold change（FC）>1 or log₂FC<-1. Kyoto Encyclopedia of Genes and Genomes（KEGG） database combined with MetaboAnalyst were used for pathway analysis of the screened differential metabolites. The protein expression levels of sphingosine-1-phosphate（S1P）， phosphatidylinositol 3-kinase（PI3K）， protein kinase B1（Akt1）， and phosphorylated Akt1（p-Akt1） were examined by Western bolt. The expression levels of interleukin（IL）-6， IL-1β， and tumor necrosis factor（TNF）-α in BALF were detected by enzyme-linked immunosorbent assay（ELISA）. ResultsCompared with the blank group， rats in the model group showed ALI pathological features such as alveolar lumen dilatation， interstitial hemorrhage and massive inflammatory cell infiltration， and the protein concentration in BALF and W/D of the lung tissues were significantly elevated（P<0.01）. Compared with the model group， the low- and high-dose groups of FF as well as the dexamethasone group exhibited reduced pulmonary bronchial hemorrhage in rats， and the protein concentration in BALF and W/D were significantly decreased（P<0.05）， and the lung injury was significantly alleviated. Analysis of rat serum metabolomics revealed that FF downregulated 38 biomarkers. Pathway enrichment analysis showed that FF primarily exerted therapeutic effects through 7 key metabolic pathways， including arginine biosynthesis， sphingomyelin metabolism， alanine， aspartate and glutamate metabolism， taurine and hypotaurine metabolism， α-linolenic acid metabolism， niacin and nicotinamide metabolism， and retinol metabolism. The results of Western bolt and ELISA showed that， compared with the blank group， the model group exhibited significantly elevated expression levels of S1P， PI3K， Akt1 and p-Akt1 proteins in the lung tissues， as well as increased expression levels of IL-6， IL-1β and TNF-α in BALF（P<0.01）. Compared with the model group， the expression levels of the aforementioned indicators were significantly downregulated in the low- and high-dose FF groups as well as the dexamethasone group（P<0.05， P<0.01）. ConclusionFF may play a role in ALI by regulating amino acid metabolism and lipid metabolism， and its mechanism may be related to the inhibition of S1P/PI3K/Akt1 signaling pathway to attenuate the inflammatory response caused by ALI.

Sweet-tasting proteins demonstrate application potential in foods and beverages due to their high sweetness, low calorie, and non-toxicity. So far, eight natural sweet-tasting proteins have been obtained from natural plants. This paper briefs the sweetness properties of the eight proteins and the molecular mechanism of the sweetness, reviews the progress in the genetic engineering, heterologous expression, and molecular modification of three representative sweet-tasting proteins (monellin, brazzein, and thaumatin), and summarizes their expression yields in different hosts and sweetness properties. Lastly, this paper prospects the research, application, and industrial development of sweet-tasting proteins. This review provides a reference for further research and development of new proteinaceous sweeteners.
Plant Proteins/biosynthesis* ; Genetic Engineering/methods* ; Sweetening Agents/chemistry* ; Plants, Genetically Modified/metabolism*

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Objective: To examine the relationship among physical education core literacy, exercise self efficacy, physical self esteem and subjective exercise experience among middle school students, and to analyze the latent classes of exercise self efficacy, so as to provide evidence for enhancing adolescents subjective exercise experience. Methods: Using stratified cluster random sampling, 2 569 students from 12 provinces, autonomous regions or municipality directly under the central govement (Jiangxi, Guangdong, Hunan, Guizhou, Henan, Guangxi, Yunnan, Chongqing, Sichuan, Shandong, Hubei, Hebei) were surveyed from September to November in 2024 with Core Competency Scale of Physical Education, Subjective Exercise Experiences Scale, Exercise Self Efficacy Scale, and Physical Self esteem Scale. Pearson correlation analysis was conducted to explore the relationships among physical education core literacy, exercise self efficacy, physical self esteem, and subjective exercise experience. Mediation models with Bootstrap testing were employed to examine the mediating roles of exercise self efficacy and physical self esteem in the relationship between physical education core literacy and subjective exercise experience. Latent profile analysis (LPA) of exercise self efficacy was performed using Mplus 8.3. Results: Pearson correlation analysis revealed positive associations between physical education core literacy and exercise self efficacy ( r =0.21), physical self esteem ( r =0.38), and subjective exercise experience ( r =0.40); exercise self efficacy was positively correlated with physical self esteem ( r =0.25) and subjective exercise experience ( r =0.45); and physical self esteem was positively correlated with subjective exercise experience ( r =0.34) (all P <0.01). Mediation analysis indicated that physical education core literacy positively predicted subjective exercise experience ( β =0.41, P <0.05), with exercise self efficacy and physical self esteem serving as partial mediators (effect size=0.14, P <0.01), accounting for 34% of the total effect. LPA identified three latent classes of exercise self efficacy:low (14.71%, n =378), moderate (65.51%, n =1 683), and high (19.78%, n =508) exercise self efficacy groups. Conclusion Adolescents exercise self efficacy demonstrates heterogeneity, and both exercise self efficacy and physical self esteem mediate the relationship between physical education core literacy and subjective exercise experience.

Objective To explore the related factors affecting the sensitivity of neoadjuvant immuno-therapy combined with chemotherapy for treating esophageal squamous cell carcinoma(ESCC).Methods The clinical data of 51 cases of ESCC were retrospectively analyzed.The patients were divided into the neoad-juvant immunotherapy combined with chemotherapy sensitivity group(n=29)and resistance group(n=22)according to the treatment effects.The statistical methods were employed to analyze the factors affecting the sensitivity of neoadjuvant immunotherapy combined with chemotherapy for treating ESCC.Results The uni-variate analysis results showed that the lesion depth detected by CT after treatment had statistical difference between the sensitivity group and resistance group(P＜0.001).The lesion depth also had statistical difference before and after treatment(P=0.002).The endoscopic evaluation showed that the proportion of the patients with pathological remission in the sensitivity group was higher than that in the resistance group with statisti-cal difference(P＜0.001).The multivariate analysis results showed that degree of pathological remission(P=0.042,95％CI:1.096-161.519)and pathological lymph node metastasis(P=0.025,95％CI:0.003-0.670)evaluated by endoscopy were the independent influencing factors of the sensitivity to neoadjuvant im-munotherapy combined with chemotherapy.Meanwhile,the patients with tumor infiltration depth difference≥0.750 cm measured by CT were more sensitive to the immunotherapy combined with chemotherapy(AUC=0.750,sensitivity 41.4％,specificity 55.0％,P=0.002,95％CI:0.618-0.882).Conclusion Preop-erative chest CT calculation of lesion depth and endoscopic assessment of pathological remission degree could predict the sensitivity of ESCC patients to neoadjuvant immunotherapy combined with chemotherapy,which provides reference for formulating the treatment regimen,however,it is necessary to enlarge the sample size and further study the various influencing factors.

Objective:To observe and analyze the effect of airflow obstruction on the inspiratory flow index and patient-ventilator synchronization in non-invasive pressure support ventilation (NI-PSV). Methods:The ASL 5000 machine simulation lung system was used to simulate health adult on semi-recumbent position and patients with chronic obstructive pulmonary disease (COPD),whose body weights were 70 kg. The models of health adult,mild obstruction,moderate obstruction and severe obstruction were set. The static compliance (Cst) of the simulated lung system was 60 mL/cmH2O,and the airway resistance (Raw) values of health adult,COPD patients with mild obstruction,moderate obstruction and severe obstruction model were respectively 5.0,10.0,15.0 and 20.0 cmH2O/(L*s),and the effort of spontaneous inhalation (Pmus) was 5.0 cmH2O,and the inspiratory time was 1.6s,and the respiratory rate was 15 times/min. Using the mode of spontaneous to time control (S/T) of Respironics V60 ventilator to operate,and the positive end-expiratory pressure (PEEP) was 5.0 cmH2O. The output tidal volume (VT) of ventilator was controlled at 7.0-8.0 mL/kg through adjusted the inspiratory pressure. The output various ventilation parameters and the change of breathing work of the simulated lung were collected,and the flow index was calculated. Results:Peak inspiratory flow (PIF) and peak expiratory flow (PEF) were decreased gradually with the severity of airflow obstruction of models of COPD patients,which inspiratory triggering flow (Flow-trig) was always remained at approximate 6.0 L/min. The value of flow index of the model with severe obstruction reached to 0.65,and the delay time (Td) of inspiratory triggering was more than 400 ms. The switching between inhalation and exhalation was from premature cycling (-469.50±16.35) ms of health adult model to mildly delayed cycling (207.25±14.86) ms,and the difference of that was significant (t=69.28,P<0.05). The inspiratory work of breathing (WOBpat) and ventilator work (WOBtot) of severe obstruction model of COPD patient were higher than those of health adults,and mild obstruction and moderate obstruction model of COPD patients,but the inspiratory work ratio (WOBpat/tot) of severe obstruction model of COPD patient was lower than that of other 3 kinds of models,and the differences were significant (F=2477.70,46960.87,51222.97,P<0.01),respectively. Conclusion:During NI-PSV support,airflow obstruction not only can decrease the value of peak airflow,change airflow shape and lead to increase the value of inspiratory flow index,but also can increase breathing work,thus affect patient-ventilator synchronization.

Objective:To observe and analyze the effect of airflow obstruction on the inspiratory flow index and patient-ventilator synchronization in non-invasive pressure support ventilation (NI-PSV). Methods:The ASL 5000 machine simulation lung system was used to simulate health adult on semi-recumbent position and patients with chronic obstructive pulmonary disease (COPD),whose body weights were 70 kg. The models of health adult,mild obstruction,moderate obstruction and severe obstruction were set. The static compliance (Cst) of the simulated lung system was 60 mL/cmH2O,and the airway resistance (Raw) values of health adult,COPD patients with mild obstruction,moderate obstruction and severe obstruction model were respectively 5.0,10.0,15.0 and 20.0 cmH2O/(L*s),and the effort of spontaneous inhalation (Pmus) was 5.0 cmH2O,and the inspiratory time was 1.6s,and the respiratory rate was 15 times/min. Using the mode of spontaneous to time control (S/T) of Respironics V60 ventilator to operate,and the positive end-expiratory pressure (PEEP) was 5.0 cmH2O. The output tidal volume (VT) of ventilator was controlled at 7.0-8.0 mL/kg through adjusted the inspiratory pressure. The output various ventilation parameters and the change of breathing work of the simulated lung were collected,and the flow index was calculated. Results:Peak inspiratory flow (PIF) and peak expiratory flow (PEF) were decreased gradually with the severity of airflow obstruction of models of COPD patients,which inspiratory triggering flow (Flow-trig) was always remained at approximate 6.0 L/min. The value of flow index of the model with severe obstruction reached to 0.65,and the delay time (Td) of inspiratory triggering was more than 400 ms. The switching between inhalation and exhalation was from premature cycling (-469.50±16.35) ms of health adult model to mildly delayed cycling (207.25±14.86) ms,and the difference of that was significant (t=69.28,P<0.05). The inspiratory work of breathing (WOBpat) and ventilator work (WOBtot) of severe obstruction model of COPD patient were higher than those of health adults,and mild obstruction and moderate obstruction model of COPD patients,but the inspiratory work ratio (WOBpat/tot) of severe obstruction model of COPD patient was lower than that of other 3 kinds of models,and the differences were significant (F=2477.70,46960.87,51222.97,P<0.01),respectively. Conclusion:During NI-PSV support,airflow obstruction not only can decrease the value of peak airflow,change airflow shape and lead to increase the value of inspiratory flow index,but also can increase breathing work,thus affect patient-ventilator synchronization.

Objective:To evaluate the clinical efficacy of omalizumab in the treatment of patients with chronic spontaneous urticaria accompanied by other allergic diseases.Methods:Clinical data were retrospectively collected from 74 patients, who were clinically diagnosed with chronic spontaneous urticaria and other allergic diseases, and received subcutaneous injections of omalizumab in the Department of Allergy, Tianjin Medical University General Hospital from June 2020 to September 2022. Types of allergic diseases, serum total IgE (tIgE) and allergen-specific IgE (sIgE) levels before treatment, treatment outcomes and adverse drug reactions were analyzed. Differences before and after treatment were assessed using paired t-test and Wilcoxon signed-rank sum test. Results:A total of 74 patients with chronic spontaneous urticaria were involved, including 29 with complicated allergic asthma (39.2%) , 61 with complicated allergic rhinitis (82.4%) , 6 with complicated atopic dermatitis (8.1%) , and 4 with food allergy (5.4%) . Before treatment, elevated serum tIgE or sIgE levels were observed in 44 (59.5%) patients. After the first omalizumab treatment, the urticaria control test (UCT) score significantly increased compared with that before treatment (16.00 [13.0.0, 16.00] vs. 6.00 [5.75, 9.00], Z = 7.39, P < 0.001) ; after 4 sessions of the omalizumab treatment, 82.5% (33/40) of the patients achieved complete control of urticaria symptoms or showed complete response. After omalizumab treatment, asthmatic attacks were decreased in 29 patients with allergic asthma, and asthma control test (ACT) scores significantly increased compared with those before treatment (21.07 ± 2.88 points [after the first treatment] vs. 18.48 ± 3.20 points [before treatment], t = 8.87, P < 0.001) ; among 61 patients with allergic rhinitis, global rhinitis symptom-based visual analog scale (VAS) scores (before treatment: 5.89 ± 1.29 points; after the first treatment: 3.28 ±1.46 points) and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores (before treatment: 60.10 ± 20.53 points; after the first treatment: 37.26 ± 18.83 points) both significantly decreased after the first treatment ( t = 15.04, 10.01, respectively, both P < 0.001) , and rhinitis symptoms were relieved at the same time; skin itching was relieved in 4 patients with atopic dermatitis, and allergic symptoms after contact with food allergens were also relieved in the 2 patients with food allergy after omalizumab treatment. During the treatment, only 1 patient experienced erythematous swelling, induration, and pain at the injection site. Conclusions:In the treatment of chronic spontaneous urticaria accompanied by allergic diseases, the use of omalizumab not only effectively improved urticaria symptoms, but also well controlled allergic diseases, with a good safety profile. Multiple benefits may be achieved by the use of omalizumabin in patients with chronic spontaneous urticaria accompanied by other allergic diseases.

ObjectiveTo investigate the preventive effect and mechanism of Aurantii Fructus Immaturus and naringin on postoperative intestinal adhesion in rats. MethodThe preventive effect of Aurantii Fructus Immaturus and naringin on intestinal adhesion was studied by cecal scraping model of rats， the model rats were randomly divided into model group， dexamethasone sodium phosphate group and Aurantii Fructus Immaturus low， medium and high dose groups （1.58， 3.15， 6.30 g·kg^-1·d^-1）， tsham-operated group was treated with an incision in the abdomen. Adhesion was assessed by Nair method after 7 d of administration. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology and inflammatory cell infiltration of cecum， the expression of matrix metalloproteinase-9 （MMP-9） in cecal adhesion was detected by immunohistochemistry. Meanwhile， intestinal adhesion model rats were randomly divided into model group， dexamethasone sodium phosphate group， naringin low， medium， high dose groups （50， 100， 200 mg·kg^-1·d^-1）， and the sham-operated group was treated with an incision in the abdomen. Adhesion was assessed after 7 d of administration， HE staining was used to observe the pathological morphology and inflammatory cell infiltration in the cecum， and the expression of MMP-9 in the cecal adhesion tissue was detected by immunohistochemistry. Expressions of transforming growth factor-β₁ （TGF-β₁） and α-smooth muscle actin （α-SMA） in cecum were analyzed by western blot. ResultAurantii Fructus Immaturus could inhibit the formation of postoperative intestinal adhesions in rats， reduce the inflammatory response of damaged cecum tissue， and up-regulate the expression of MMP-9 in the adherent tissue in a dose-dependent manner. All dose groups of naringin could significantly inhibit the formation of postoperative intestinal adhesions in rats， reduce inflammatory cell infiltration and fibrous proliferation in tissue， up-regulate the expression of MMP-9 in the adherent tissue in a dose-dependent manner， and inhibit the expression of TGF-β₁ and α-SMA in cecal tissue. ConclusionAurantii Fructus Immaturus and naringin can reduce postoperative intestinal adhesion formation in rat model， and their effects may be related to reducing tissue fibrosis and accelerating extracellular matrix degradation.