This study investigates the material basis and mechanism of Arisaematis Rhizoma Preparatum in the treatment of chronic obstructive pulmonary disease(COPD) using animal experiments, component analysis, network pharmacology, and molecular docking. A mouse model of COPD was constructed by cigarette smoke and lipopolysaccharide(LPS). Blood gas analysis was performed to measure the pH and partial pressure of carbon dioxide(PCO_2) in the blood of the mice. Lung tissue sections were analyzed using HE staining, and the effects of Arisaematis Rhizoma Preparatum water extract on inflammatory factors(TNF-α, IL-6, and IL-1β) and the PI3K/AKT signaling pathway in the lung tissue of COPD model mice were studied by qPCR and Western blot. The composition of the Arisaematis Rhizoma Preparatum water extract was analyzed using UPLC Q-Exactive Orbitrap MS. The SwissTargetPrediction database was used to predict the targets of the chemical components in Arisaematis Rhizoma Preparatum. GeneCards, OMIM, TTD, PharmGKB and DrugBank disease databases were used to screen for COPD targets, and the potential targets of Arisaematis Rhizoma Preparatum in treating COPD were identified. A protein-protein interaction(PPI) network of intersection targets was constructed and analyzed using the STRING database and Cytoscape 3.9.0, and core genes were screened. GO functional analysis and KEGG pathway enrichment analysis were performed using R language, and molecular docking verification was conducted using AutoDock Vina software. The results of the animal experiments showed that Arisaematis Rhizoma Preparatum water extract improved pulmonary ventilation function in COPD model mice, reduced lung inflammatory cells, decreased alveolar cavities, and improved lung tissue condition. The levels of inflammatory factors TNF-α, IL-6 and IL-1β were decreased, and the phosphorylation levels of PI3K and AKT were inhibited. Fifty-two chemical components were identified from Arisaematis Rhizoma Preparatum, and 440 intersection targets related to COPD were found. Nine key components were screened, including hydroxyphenylethylamine, L-tyrosine, L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, methyl azelate, zingerone, 6-gingerol, linoleamide, and linoleoyl ethanolamine. Five core targets were identified, including AKT1, TNF, STAT3, ESR1, and IL1B. The PI3K/AKT pathway was identified as the key pathway for the treatment of COPD with Arisaematis Rhizoma Preparatum. Molecular docking results showed that 75% of the binding energies of key components and core targets were less than-5 kcal·mol~(-1), indicating good binding affinity. In conclusion, Arisaematis Rhizoma Preparatum may improve pulmonary ventilation function, enhance lung pathological morphology, and reduce pulmonary inflammation in COPD model mice by inhibiting the PI3K/AKT signaling pathway and downregulating TNF-α, IL-6, and IL-1β inflammatory factors. The material basis may be associated with L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, zingerone and 6-gingerol, and AKT1 and TNF may be the primary targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rhizome/chemistry* ; Humans ; Molecular Docking Simulation ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Signal Transduction/drug effects* ; Lung/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Interleukin-6/immunology*

OBJECTIVE: Asthma imposes a significant global health burden. This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios. METHODS: Using data from the Global Burden of Disease 2021 study, we analyzed asthma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled. Temporal trends in age-standardized incidence, prevalence, mortality, and DALY rates were explored using Annual Percent Change. RESULTS: In 2021, the age-standardized rates for asthma incidence, prevalence, mortality, and DALYs in China were 364.17 per 100,000 (95% uncertainty interval [ UI]: 283.22-494.10), 1,956.49 per 100,000 (95% UI: 1,566.68-2,491.87), 1.47 per 100,000 (95% UI: 1.15-1.79), and 103.76 per 100,000 (95% UI: 72.50-145.46), respectively. A higher disease burden was observed among Chinese men and individuals aged 70 years or older. Compared to the current trend, a combined scenario involving improvements in environmental factors, behavioral and metabolic health, child nutrition, and vaccination resulted in a greater reduction in the disease burden caused by asthma. CONCLUSION Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
Humans ; Asthma/mortality* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Child ; Adolescent ; Global Burden of Disease/trends* ; Child, Preschool ; Young Adult ; Infant ; Cost of Illness ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Infant, Newborn ; Aged, 80 and over ; Risk Factors

Objective To establish and validate a multimodal MRI radiomics model based on intratumoral and peritumoral heterogeneity for prediction of spatial pattern of locally recurrent high-grade gliomas(HGGs).Methods A retrospective analysis was conducted on the clinical and imaging data of all HGGs patients who underwent maximum safe resection followed by postoperative radiotherapy combined with temozolomide treatment and experienced in local recurrence in Army Medical Center of PLA from 2012 to 2021.Two radiologists independently assessed the spatial patterns of locally recurrence HGGs through continuous follow-up MRI data,and primarily categorized the pattern into intra-resection cavity recurrence and extra-resection cavity recurrence.The subjected patients were randomly divided into a training set and a validation set in a 7∶3 ratio.In the training set,Pearson or Spearman correlation analysis and least absolute shrinkage and selection operator(LASSO)analysis were employed to screen radiomic features within the intratumoral and peritumoral regions,as well as to calculate radiomic scores.A radiomics model was established using logistic regression analysis.The performance of the model was assessed using calibration curves,Hosmer-Lemeshow goodness-of-fit test,and the area under the receiver operating characteristic curve(AUC).Validation of the model was performed in the validation set.Results A total of 121 patients with locally recurrent HGGs were enrolled in this study,including 54 in intra-resection cavity recurrence group and 67 in extra-resection cavity recurrence group.Among them,84 were assigned into the training set and 37 into the validation set.In the training set,the radiomics score for the extra-resection cavity recurrence group was 0.424(0.278,0.573),which was higher than that for the intra-resection cavity recurrence group[-0.030(-0.226,0.248),P<0.001].In the validation set,the radiomics score for the extra-resection cavity recurrence group was 0.369(0.258,0.487),which was higher than that for the intra-resection cavity recurrence group[0.277(0.103,0.322),P=0.033].The established radiomics model exhibited good calibration and performed well in predicting spatial recurrence patterns,with an AUC value of 0.844(95%CI:0.749～0.914)in the training set and 0.706(95%CI:0.534～0.844)in the validation set.Conclusion Our multimodal radiomics model combined with intratumoral and peritumoral heterogeneity can predict the spatial pattern of locally recurrent HGGs,providing a basis for individualized treatment of HGGs.

AIM: To assess the repeatability and agreement of higher-order aberration obtained by adaptive optics visual simulator(VAO)compared with OPD-Scan Ⅲ.METHODS: A cross-sectional study was conducted from August to September 2023, including a total of 204 patients(204 eyes)with myopia whose right eyes were measured. The examinations were performed by the same skilled examiner using both devices separately. The VAO device was used to measure higher order aberrations of orders 3 to 6 at a pupil diameter of 4.5 mm, while both the VAO and OPD-Scan Ⅲ devices were utilized to measure total higher-order aberration(tHOA), spherical aberration(SA), coma aberration(Coma), and trefoil aberration(Trefoil)of the entire eye at pupil diameters ranging from 3 to 6 mm. Furthermore, the repeatability of whole eye aberration measurements obtained with the VAO device was evaluated and the agreement of the two devices was assessed.RESULTS: The whole-eye higher-order aberrations measured by VAO demonstrated excellent repeatability(0.767≤ICC≤0.941, Sw<0.01 μm, TRT<0.1 μm). There was no statistically significant difference in Coma measured by VAO or OPD-Scan Ⅲ for pupil diameters ranging from 4 to 6 mm(P>0.05), while a statistically significant difference was observed in whole-eye tHOA of other pupil diameters(all P<0.05). The agreement of aberration measurements for each order between VAO and OPD-Scan Ⅲ for 3 mm pupil diameters, SA at 4 and 5 mm pupil diameter and Coma at 4 mm pupil diameter showed a 95% limit of agreement(LoA)<0.1, indicating good agreement; however, poor agreement was found for the remaining aberration measurements at different pupil diameters, with a 95%LoA>0.1, and there were significant differences in higher-order aberrations measured by two devices under a pupil diameter of 3 mm(r=0.218-0.317, P<0.01), 4 mm(r=0.406-0.672, P<0.01), 5 mm(r=0.538-0.839, P<0.01 and r=0.030-0.109, P>0.01)and 6 mm(r=0.369-0.766, P<0.01).CONCLUSION: The VAO demonstrates favorable repeatability when assessing whole-eye higher order aberration under pupil diameters of 3-6 mm. However, there is inadequate agreement and interchangeability in whole-eye higher order aberration at 3-6 mm pupil diameter between VAO and OPD-Scan Ⅲ for clinical purposes.

Objective:To investigate the therapeutic effect of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive positive pressure ventilation (NPPV) on patients with pulmonary edema caused by seawater drowning.Methods:A retrospective analysis method was used. Based on the Utstein database of emergency drowning in the First Hospital of Qinhuangdao, the clinical data of patients with seawater drowning pulmonary edema admitted to the emergency medicine department of the First Hospital of Qinhuangdao from January 1, 2019 to December 31, 2022 were collected. The patients were divided into NPPV group and HFNC group according to different ventilation methods. The general data, endotracheal intubation rate in 7 days, arterial blood gas analysis indexes [arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), arterial oxygen saturation (SaO 2)] and hemodynamic indexes (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, blood lactic acid) before and after treatment, length of stay in intensive care unit (ICU), oxygen therapy comfort of the two groups were compared. Results:A total of 54 patients were enrolled, including 21 patients in the NPPV group and 33 patients in the HFNC group. There were no significant differences in gender, age, state of consciousness and other general information between the two groups. Compared with NPPV group, the rate of endotracheal intubation in HFNC group within 7 days was significantly lower [24.2% (8/33) vs. 33.3% (7/21), P < 0.05]. Before treatment, there were no significant differences in arterial blood gas analysis and hemodynamics between the two groups. After treatment, the above indexes in both groups were significantly improved compared with those before treatment, and PaO 2, SaO 2, systolic blood pressure, diastolic blood pressure and mean arterial pressure in HFNC group were significantly higher than those in NPPV group [PaO 2 (mmHg, 1 mmHg≈0.133kPa): 93.56±6.37 vs. 82.14±6.25, SaO 2: 1.02±0.09 vs. 0.95±0.11, systolic blood pressure (mmHg): 117.37±8.43 vs. 110.42±8.38, diastolic blood pressure (mmHg): 79.43±7.61 vs. 72.21±4.32, mean arterial pressure (mmHg): 92.34±6.32 vs. 85.12±5.38], PaCO 2, heart rate and blood lactic acid were significantly lower than those in NPPV group [PaCO 2 (mmHg) : 34.26±5.63 vs. 37.24±6.22, heart rate (times/min): 73.38±7.56 vs. 86.25±5.41, blood lactic acid (mmol/L): 1.38±0.36 vs. 2.25±1.14], and the differences were statistically significant (all P < 0.05). In addition, the length of ICU stay in HFNC group was significantly shorter than that in NPPV group (days: 13.30±2.38 vs. 16.27±4.26), and the comfort rate of oxygen therapy was significantly higher than that in NPPV group [66.7% (22/33) vs. 42.8% (9/21)], with statistical significance (all P < 0.05). Conclusion:HFNC can improve the oxygenation of patients with pulmonary edema caused by seawater drowning, improve hemodynamics, reduce the rate of tracheal intubation, shorten the length of ICU stay, and improve the comfort of oxygen therapy, which has certain clinical application value.

ObjectiveTo investigate the possible mechanism of electroacupuncture at "Neiguan" （PC6） and "Zhongwan" （RN12） in the treatment of functional dyspepsia （FD）. MethodsSPF male SD rats were randomly divided into model group， Neiguan （PC6） group， Zhongwan （RN12） group， and Neiguan-Zhongwan （PC6-RN12） group， with 8 rats in each group. Except for the normal group， the other groups of rats were cogavaged with 0.1% sucrose iodoacetamide solution combined with small platform standing training to establish FD rat models. After successful modeling， the rats in the normal group and model group were tied up for 30 min/d for 7 days； the Neiguan group， Zhongwan group， and Neiguan-Zhongwan group were treated with electroacupuncture intervention at "Neiguan" （PC6）， "Zhongwan" （RN12）， and "Neiguan" - "Zhongwan" （PC6-RN12） acupoints， respectively， using continuous wave， frequency of 2 Hz， current intensity of 1 mA， 30 min/d， and continuous intervention for 7 days. The general condition of rats in each group was observed. After treatment， the body weight and food intake of rats were measured， and the gastric emptying rate was calculated； HE staining was performed on the gastric antrum tissue of rats to observe the histopathologic changes； the expressions of calcitonin gene-related peptide （CGRP） and Ghrelin protein in gastric antrum were detected by Western Blot； the metabolites in gastric antrum tissues were detected by liquid chromatography-mass spectrometry （LC-MS）， and differential metabolites were screened by correlation analysis， then Metabo Analyst 5.0 and KEGG databases were used for metabolic pathway analysis. ResultsUnder light microscope， the gastric antrum structure was complete and the glands were abundant. No obvious inflammation and edema were found in gastric mucosa. Compared with the normal group， the body weight， food intake， and gastric emptie rate of rats in model group decreased， the expression of Ghrelin protein decreased and the expression of CGRP protein increased in gastric antrum tissue （P＜0.01）. Compared with model group， the body weight， food intake， and gastric emptance rate of rats in Neiguan group， Zhongwan group and Neiguan-Zhongwan group all increased， CGRP protein expression decreased in Neiguan group， and Ghrelin protein expression increased and CGRP protein expression decreased in Zhongwan group and Neiguan-Zhongwan group （P＜0.01 or P＜0.05）. Compared with Neiguan-Zhongwan group， Ghrelin protein expression decreased and CGRP protein expression increased in Neiguan group and Zhongwan group （P＜0.05 or P＜0.01）. Metabolomics results showed that compared with normal group， the content of metabolites adenosine diphosphate ribose， adenosine monophosphate and adenosine diphosphate in gastric antrum tissue of model group decreased； compared with model group， the contents of adenosine diphosphate， adenosine diphosphate and citicoline in Neiguan group increased， the contents of nicotine adenine dinucleotide， cytidine diphosphate ethanolamine and citicoline in Zhongwan group increased， and the contents of adenosine diphosphate， cytidine diphosphate and citicoline in Neiguan-Zhongwan group increased （P＜0.05 or P＜0.01）. Compared with model group， the main metabolic pathways of different metabolites in PC6-RN12 group were glycerophospholipid metabolism， taurine and hypotaurine metabolism， purine metabolism， starch and sucrose metabolism. ConclusionElectroacupuncture at “Neiguan” and “Zhongwan” acupoints can effectively regulate gastrointestinal motility and improve FD symptoms in FD rats， and the effect is better than that of "Neiguan" or "Zhongwan" acupoints alone. The mechanism may be related to the influence of related metabolites on energy metabolism， glucose metabolism and nucleotide metabolism， thereby regulating gastrointestinal motility hormones.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Objective To investigate the clinical efficacy and safety of Zishen Jianpi Quyu Formula in treating patients with migraine without aura in the postmenstrual period of kidney deficiency and blood stasis type.Methods A total of 104 patients with migraine without aura of kidney deficiency and blood stasis type were randomly divided into the control group and the trial group,with 52 cases in each group.The control group was treated with Flunarizine Hydrochloride Capsules,and the trial group was treated with Zishen Jianpi Quyu Formula on the basis of treatment for the control group.One menstrual cycle constituted a course of treatment,and the treatment covered a total of two courses(eight weeks).The changes of traditional Chinese medicine(TCM)syndrome score,migraine attack frequency,duration of migraine headaches,visual analogue scale(VAS)score of migraine headache intensity,Headache Impact Test-6(HIT-6)score and hemorheology indexes in the two groups before and after treatment were observed.Moreover,the efficacy for TCM syndrome and clinical safety in the two groups were evaluated.Results(1)After two courses of treatment,the total effective rate of the trial group was 90.38%(47/52),and that of the control group was 69.23%(36/52),the intergroup comparison(by chi-square test)showed that the efficacy for TCM syndrome in the trial group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores of the patients in both groups were significantly lower than those before treatment(P＜0.05),and the reduction of TCM syndrome score in the trial group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the migraine attack frequency,duration of migraine headaches,VAS scores of migraine headache intensity in the two groups of patients were significantly improved compared with those before treatment(P＜0.05),and the improvement of migraine headache parameters in the trial group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the HIT-6 score in the two groups was decreased significantly compared with those before treatment(P＜0.05),and the decrease of HIT-6 score in the trial group was significantly superior to that in the control group(P＜0.05).(5)After treatment,hemorheology indexes(including plasma viscosity,whole blood high-shear viscosity,whole blood low-shear viscosity,fibrinogen,and hematocrit)in the two groups were improved compared with those before treatment(P＜0.05),and the improvement of each of hemorheology indexes in the trial group was significantly superior to that in the control group(P＜0.05).(6)During treatment,no serious adverse events occurred in the two groups,which was of high safety.Conclusion Zishen Jianpi Quyu Formula exerts remarkable clinical efficacy in treating patients of migraine without aura in the postmenstrual period of kidney deficiency and blood stasis type.The formula is effective on improving the TCM syndromes and migraine attacks of the patients,achieving the efficacy of milder headache,lower attack frequency and shorter duration,more stability hemorheology indexes and higher safety.

Objective:To compare the differences in prefrontal activation patterns between major depressive disorder and schizophrenia during the eye basic emotion discrimination task (EBEDT).Methods:Using functional near infrared spectroscopy (fNIRS) technology and block design, the changes of prefrontal lobe oxyhemoglobin (Oxy-Hb) concentrations under EBEDT in 40 patients with major depressive disorder, 47 patients with schizophrenia and 55 normal controls were compared. Subsequently, employing years of education as a covariate, an analysis of covariance was performed on the EBEDT behavioral results and the changes in prefrontal Oxy-Hb concentrations in the three groups.The statistical software was SPSS 25.0.Results:(1)The correct number of EBEDT in schizophrenia group (13.93±7.67) was significantly lower than that in major depressive disorder group (19.26±8.07) and normal control group (21.79±6.36)(both P<0.05), and the EBEDT reaction time in schizophrenia group ((3.97±1.77) s) was significantly longer than those in major depressive disorder group ((3.21±1.27) s) and normal control group ((2.63±0.62) s)(both P<0.05).(2)During the EBEDT task block, the normal control group showed increased activation levels in the frontal polar region, Broca's area, anterior motor cortex and supplementary motor area (SMA) compared with the control block( t=2.02-3.18, all P<0.05); and the schizophrenia group showed increased activation levels in the frontal eye field compared with the control block( t=2.26, P=0.03); while the major depressive disorder group exhibited decreased activation levels in the entire prefrontal lobe compared with the control block( t=-3.47--2.34, all P<0.05). (3)During the emotion recognition task of EBEDT, the activation levels of the frontal polar area (ch37), dorsolateral prefrontal cortex (ch31), Broca's area (ch49, ch51, ch53), and SMA (ch1, ch47, ch52) were significantly different among the major depressive disorder, schizophrenia and normal controls( F=3.23-5.53, all P<0.05). Further pairwise comparisons showed that the activation levels in all the above pathways were lower in the major depressive disorder group than those in the normal control group, and the activation levels in Broca's area (ch53) and SMA area (ch52) were lower in the schizophrenia group than those in the normal control group, while the activation levels in the frontal polar area (ch37) and Broca's area (ch49) were lower in the major depressive disorder group than those in the schizophrenia group(all P<0.05). Conclusions:In EBEDT, the activation patterns of the prefrontal cortex are different between patients with major depressive disorder and patients with schizophrenia. Patients with major depressive disorder have a decrease in prefrontal cortex activation, while patients with schizophrenia have an increase in the frontal eye field activation.The activation levels in prefrontal cortex of both patients group are lower than that of normal controls. Meanwhile, the prefrontal cortex activation level of patients with major depressive disorder is lower than that of patients with schizophrenia.

Aim To study the effect of emetine on in-sulin secretion through glucagon-like peptide-1 receptor(GLP-1R).Methods Isolating rat islets were used to carry out insulin secretion experiment.Islets were incubated with different concentrations of emetine(2,10,50 μmol·L-1),different concentrations of glu-cose solution(2.8,11.1,16.7 mmol·L-1)or spe-cific GLP-1R antagonist Exendin(9-39).The amount of insulin secretion in the supernatant of each group was determined by an enzyme-linked radioimmunoas-say.Small molecule compounds were docked to GLP-1R(PDB code:5NX2)using SYBYL-X2.0 software.Results Emetine could promote insulin secretion in high glucose(11.1 mmol·L-1)in a dose-dependent manner.In low glucose(2.8 mmol·L-1),insulin secretion did not change after intervention of emetine.But in high glucose(11.1,16.7 mmol·L-1),insu-lin secretion significantly increased under the treatment of emetine in a glucose-dependent manner.The doc-king score of emetine and GLP-1R was Total Score=6.82,C Score=5,indicating that emetine had a good binding affinity with GLP-1R.Using Exendin(9-39)to block GLP-1R,the insulinotropic effect of emetine was reduced.Conclusion Emetine could promote in-sulin secretion,which is related to the activation of GLP-1R.