1.Conbercept therapy for neovascular age-related macular degeneration under the treat-and-extend regimen
Linrui LI ; Jun LI ; Yun LYU ; Mingyue ZHANG ; Moxiu GU
International Eye Science 2026;26(5):738-745
AIM:To assess the efficacy of intravitreal conbercept for treating neovascular age-related macular degeneration(nAMD)under a treat-and-extend(T & E)regimen.METHODS: A retrospective analysis was conducted on nAMD patients followed over a 2-year period(May 2020 to May 2022). All eyes received three monthly loading intravitreal injections of conbercept, followed by a T& E regimen in which the injection interval was extended by 2 or 4 wk according to disease activity, up to a maximum of 16 wk. When disease activity recurred, the interval was shortened. Patients were divided into initial and non-initial treatment groups based on treatment history. Best-corrected visual acuity(BCVA), central macular thickness(CMT), injection frequency, and intervals between injections over the 24-month follow-up were compared.RESULTS:Totally 27 patients(15 males and 12 females, 33 eyes)were enrolled. In the initial treatment group(18 eyes, mean age 65.72±12.32 y), BCVA significantly improved at 1, 3, and 6 mo(P<0.05), and CMT significantly improved at 1 and 3 mo(P<0.05). In the non-initial treatment group(15 eyes, mean age 69.00±9.21 y), BCVA improved significantly at 3 mo(P<0.05), whereas CMT remained stable(P >0.05). Baseline CMT was similar between the groups(P>0.05). However, significant differences were observed at multiple post-injection time points(P<0.05). The total number of injections did not differ between the groups(P>0.05). Intervals between injections varied, with the majority at 4 and 3-4 mo in the initial and non-initial treatment groups, respectively.CONCLUSION:Initiating intravitreal conbercept therapy under a T & E regimen results in superior visual and anatomical outcomes compared with non-initial treatment.
2.Improvement effects and mechanisms of Suting pingchuan decoction in rats with bronchial asthma
Mengyin LI ; Guihua SONG ; Mingyue REN ; Wangmeng CHAI
China Pharmacy 2026;37(10):1251-1257
OBJECTIVE To explore the improvement effects of Suting pingchuan decoction (STPC) on bronchial asthma in rats and its potential mechanism. METHODS Male SD rats were randomly divided into blank group, model group, STPC low-, medium- and high-dose groups (4.14, 8.28, and 16.56 g/kg, respectively, based on the crude drug dosage), and dexamethasone group (positive control, 1 mg/kg), with 8 rats in each group. Except for the blank group, the other groups were sensitized by intraperitoneal injection of ovalbumin and challenged by nebulized inhalation of ovalbumin to establish a bronchial asthma model. From the day of nebulization challenge, rats of each group were administered the corresponding drug solution or normal saline by gavage 1 hour before aerosolization, once a day, for 7 consecutive days. During the experiment, behavioral changes in rats of each group were observed. After the last administration, the levels of inflammatory factors (interleukin-1β, interleukin-18) in bronchoalveolar lavage fluid (BALF), and oxidative stress indexes [malondialdehyde (MDA), superoxide dismutase (SOD)] in lung tissue were determined; pathological changes in lung tissue were observed; cell apoptosis in lung tissue, and the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) and the protein expressions of NLRP3, cleaved caspase-1, caspase-1, gasdermin D (GSDMD) and gasdermin D-N-terminal domain (GSDMD-N) in lung tissue were detected. RESULTS Compared with the blank group, rats in the model group showed symptoms such as scratching their ears and noses and frequent sneezing; the lung tissue structure was severely damaged, and there was obvious inflammatory cell infiltration. The levels of inflammatory factors in BALF, as well as the level of MDA, TUNEL-apoptotic cell rate, the mRNA expression of NLRP3, and the protein expressions of NLRP3, cleaved caspase-1, caspase-1, GSDMD-N and GSDMD in lung tissue were significantly increased or up-regulated, while the level of SOD in lung tissue was significantly decreased ( P <0.05 or P <0.01). Compared with the model group, the above symptoms and pathological damages of lung tissue in each drug group were significantly improved, and all quantitative indicators (except for the protein expressions of GSDMD in the STPC groups, as well as the level of SOD, and the protein expressions of cleaved caspase-1, caspase-1 and GSDMD-N in the STPC low-dose group) were significantly reversed ( P <0.05 or P <0.01). CONCLUSIONS STPC can improve airway inflammation and lung tissue damage in rats with bronchial asthma, reduce the level of oxidative stress, and decrease the release of inflammatory factors such as IL-1β and IL-18. Its mechanism of action may be related to the inhibition of pyroptosis activation mediated by the NLRP3/caspase-1/GSDMD signaling pathway.
3.Exploring Mechanism of Modified Danggui Yinzi in Regulating "Itch-anxiety" Cycle of Chronic Urticaria Based on STEP/NR2B Signaling Pathway
Mingyue LI ; Xinyu XIAO ; Anjing CHEN ; E LIU ; Xurui WANG ; Qin ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):123-133
ObjectiveTo explore the effects and mechanism of the modified Danggui Yinzi on "itch-anxiety" model rats of chronic urticaria (CU). MethodsThe 36 SPF-grade 6-8-week-old female SD rats were randomly divided into a blank control group,a model group,a positive control group,a low-dose modified Danggui Yinzi group,a medium-dose modified Danggui Yinzi group,and a high-dose modified Danggui Yinzi group. A "itch-anxiety" model was established by intraperitoneal injection of a suspension of sodium chloride and aluminum hydroxide and ovalbumin,combined with chronic unpredictable emotional stress stimulation. After successful modeling,rats in each group were administered drugs by gavage. The positive control group was given intragastric administration of the drug solutions of cetirizine and fluoxetine (2.08 mg·kg-1·d-1 fluoxetine, 2 mg·kg-1·d-1 cetirizine), the low-,medium-,and high-dose modified Danggui Yinzi groups were administered traditional Chinese medicine at 1.44,2.88, 5.76 g·kg-1, respectively,while the blank control group and model group were given an equal volume of normal saline. All interventions lasted for 15 days. Behavioral changes were evaluated by the elevated plus-maze test (detecting the percentage of entries into the open arms (OE%),the percentage of time spent in the open arms (OT%),and the total number of entries into the open and closed arms (TNE)),the open-field test (detecting total activity,average movement speed,and latency to enter the central area),and scratching behavior observation. Pathological changes of skin tissues were observed by hematoxylin-eosin (HE) staining and toluidine blue staining,while those of amygdala tissues were observed by HE staining,Nissl staining,and immunofluorescence detection of ionized calcium-binding adapter molecule-1 (Iba-1). The content of immunoglobulin E (IgE),interleukin-33 (IL-33),histamine in serum and glutamate in the amygdala was detected by enzyme-linked immunosorbent assay (ELISA). Western blot was used to detect the protein expression of striatal-enriched protein tyrosine phosphatase (STEP),N-methyl-D-aspartate receptor subunit 2B (NR2B), calmodulin-dependent protein kinase Ⅱ (CaMKⅡ),phosphorylated CaMKⅡ (p-CaMKⅡ),mitogen-activated protein kinase (MAPK),phosphorylated MAPK (p-MAPK),nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB),phosphorylated NF-κB (p-NF-κB),and postsynaptic density protein-95 (PSD-95) in the amygdala. ResultsCompared with the blank control group,the model group rats showed obvious anxiety-like behaviors (decreased OE%,OT%,and TNE,reduced total activity,slower average movement speed,and prolonged latency to enter the central area),increased scratching times,obvious skin inflammation and mast cell degranulation,severe amygdala tissue damage,increased glutamate content in the amygdala,and elevated levels of IgE and IL-33 in serum. The expression of STEP,NF-κB,p-NF-κB,NR2B,MAPK,p-MAPK,CaMKⅡ,and p-CaMKⅡ proteins in the amygdala increased,while the expression of PSD-95 protein decreased (P<0.05). Compared with the model group,the modified Danggui Yinzi group of each dose had increased OE%,OT%,TNE,total activity,and average movement speed,shortened latency to enter the central area, reduced scratching times,alleviated skin inflammation and mast cell degranulation,relieved amygdala tissue damage,decreased glutamate content in the amygdala,and reduced levels of IgE and IL-33 in serum. Moreover,compared with the model group,the low -,medium-,and high-dose modified Danggui Yinzi groups showed decreased expression levels of STEP,NF-κB,p-NF-κB,NR2B,MAPK,p-MAPK,CaMKⅡ,and p-CaMKⅡ proteins in the amygdala,and increased expression of PSD-95 protein. There was a significant dose-effect relationship,with the high-dose group showing the most significant regulatory effect (P<0.05). ConclusionThe modified Danggui Yinzi has a therapeutic effect on "itch-anxiety" model rats of CU. Its mechanism may be related to regulating glutamate metabolism in the amygdala,modulating the STEP/NR2B/CaMKⅡ/MAPK/NF-κB pathway,and regulating the expression of PSD-95.
4.Latent profiles of family intergenerational transmission and their association with proactive health behaviors among overweight and obesity junior high school students
LI Jingjing, ZHOU Yunping, HU Tian, ZHAO Mingyue, ZHOU Ziyue
Chinese Journal of School Health 2026;47(7):935-940
Objective:
To identify the latent profile characteristics and associated factors of family intergenerational transmission of proactive health behaviors in overweight and obesity junior high school students, so as to provide a reference for promoting active health in adolescents.
Methods:
From October to December 2024, a stratified cluster random sampling method was employed to select 4 932 junior high school students with overweight and obesity from 18 junior high schools of three cities representing the eastern (Yantai), central (Zibo), and western (Zaozhuang) regions of Shandong Province. Latent profile analysis was used to explore the heterogeneity of family intergenerational transmission among those students. Univariate analysis and multiple Logistic regression analysis were conducted to identify factors associated with different profiles and to examine the influence of profile membership on junior high school students proactive health levels.
Results:
The intergenerational transmission of health behaviors in junior high school students could be classified into 3 latent profiles:the moderate modeling dysfunctional group (5.88%, n =290), the low modeling advantage deficient group (41.79%, n =2 061), and the high modeling functional harmonious group ( 52.33 % n =2 581). Univariate analysis showed that gender, urban/rural area, region location, paternal/maternal education level, family economic status, and only child status were significantly associated with the classification of latent profiles of intergenerational transmission in families of overweight and obesity junior high school students ( χ 2=7.63-165.22, all P <0.05). Multiple Logistic regression analysis revealed that, using the moderate modeling dysfunctional group as the reference, male students ( OR =0.71) and those residing in coastal cities ( OR =0.74) were less likely to belong to the low modeling advantage deficient group (both P <0.05); students with moderate family economic status were more likely to belong to the low modeling advantage deficient group ( OR =1.72, P <0.05). Conversely, students living in urban areas ( OR =1.43), those with fathers ( OR =2.53) or mothers ( OR =2.48) having a college degree or above, and those with moderate ( OR =3.89) or good ( OR =2.42) family economic status were more likely to be classified into the high modeling functional harmonious group (all P < 0.05 ). Using the low modeling advantage deficient group as the reference, residing in coastal cities ( OR =1.26), living in urban residence ( OR =1.14), having parents (father or mother) with a college education or above ( OR =1.91, 2.33), moderate or good family economic status ( OR = 2.27 , 3.17), and being an only child ( OR =1.19) were associated with a higher probability of belonging to the high modeling functional harmonious group (all P < 0.05 ). There was a statistically significant difference in active health behaviors among students across different latent profiles of family intergenerational transmission ( F =494.79, P <0.01).
Conclusions
The heterogeneity of family intergenerational transmission is associated the level of proactive health behaviors among junior high school students. Therefore, precision interventions should be implemented based on different categories of family intergenerational transmission, so as to strengthen the efficacy of intergenerational transmission of health behaviors and promote proactive health among junior high school students.
5.Research progress in machine learning-assisted individualized vancomycin medication
Mingyue CHEN ; Yifei LEI ; Xuewu SONG ; Jinqi LI
China Pharmacy 2026;37(17):2310-2314
Vancomycin is a glycopeptide antibiotic widely used for severe infections caused by gram-positive bacteria. Nevertheless, its clinical application is limited by a narrow therapeutic window and inter-individual differences in pharmacokinetics. Conventional dosing regimens rely on clinical experience and population pharmacokinetic models, which make precise therapy difficult. The emergence of machine learning provides new insights into tackling the above challenges. By integrating multi-dimensional data including demographic characteristics, clinical indicators and combined medications, machine learning can assist individualized medication for patients and improve the capacity for vancomycin dose prediction, in vivo exposure assessment and renal toxicity risk warning. However, the application of machine learning still faces multiple challenges such as poor data quality, weak model generalization ability and insufficient interpretability. Its clinical value needs to be further confirmed by prospective studies and external validation. Future research may consider deep integration of machine learning and population pharmacokinetic models to better support vancomycin individualized medication.
6.Huoxue Wentong Prescription Ameliorates Post-myocardial Infarction Ventricular Remodeling in Rats via HIF-1α/TGF-β1/POSTN-mediated Regulation of EndMT
Xiaoning SUN ; Xiaoxiao ZHANG ; Cheng LI ; Qingqing WANG ; Jianguo LIN ; Mingyue WANG ; Ying YANG ; Kuiwu YAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(22):148-158
ObjectiveTo explore the potential mechanism by which Huoxue Wentong prescription (HXWT) ameliorates post-myocardial infarction (MI) ventricular remodeling by regulating endothelial-to-mesenchymal transition (EndMT) via the hypoxia-inducible factor-1α (HIF-1α)/transforming growth factor-β1 (TGF-β1)/periostin (POSTN) signaling pathway. MethodsEighty SPF-grade male Sprague-Dawley rats were randomly assigned to a sham-operated group (n=10) and a modeling group (n=70). The MI model was established by left anterior descending coronary artery ligation. Successfully modeled rats were further randomized into a model group, a sacubitril/valsartan (Entresto, 0.021 g·kg-1) group, and low, medium, and high-dose (4.15, 8.30, and 16.60 g·kg-1, respectively) HXWTF groups (n=10 per group). From postoperative day 2, rats received HXWTF or sacubitril/valsartan by gavage once daily for 4 weeks, and those in sham and model groups received an equal volume of normal saline. After intervention, general conditions were assessed. Echocardiography was performed to measure the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end diastolic diameter (LVEDD), and left ventricular end systolic diameter (LVESD). Hematoxylin and eosin (HE) staining was employed to evaluate myocardial histopathology, and Masson's trichrome staining to assess myocardial fibrosis. Serum levels of B-type natriuretic peptide (BNP), interleukin (IL)-6, IL-10, and matrix metalloproteinase-9 (MMP-9) were determined by enzyme-linked immunosorbent assay (ELISA). Collagen type Ⅰ (ColⅠ) expression was assessed by immunohistochemistry. Immunofluorescence double staining was adopted to detect the expression of platelet endothelial cell adhesion molecule-1 (CD31) and α-smooth muscle actin (α-SMA). Western blot was performed to quantify the expression of collagen type Ⅰ α2 (Col1A2), VE-cadherin, CD31, α-SMA, HIF-1α, TGF-β1, and POSTN. ResultsCompared with the sham group, the model group exhibited thinning and collapse of the left ventricular wall, decreased LVEF and LVFS and increased LVEDD and LVESD (P<0.01), disrupted myocardial fibers with marked inflammatory cell infiltration, increased collagen deposition, enhanced ColⅠ immunoreactivity, elevate serum BNP, IL-6, and MMP-9 levels, a reduced IL-10 level (P<0.01), downregulated expression of CD31 and VE-cadherin, and upregulated expression of α-SMA, Col1A2, HIF-1α, TGF-β1, and POSTN (P<0.05,P<0.01), accompanied by increased CD31/α-SMA co-localization. Compared with the model group, the sacubitril/valsartan group and all HXWTF groups showed improved ventricular wall structure, increased LVEF and LVFS, decreased LVEDD and LVESD, attenuated myocardial injury with reduced inflammatory infiltration and collagen deposition, declined serum BNP, IL-6, and MMP-9 levels, an elevated serum IL-10 level, upregulated expression of CD31 and VE-cadherin, downregulated expression of α-SMA, Col1A2, HIF-1α, TGF-β1, and POSTN, and reduced CD31/α-SMA co-localization (P<0.05,P<0.01). No significant differences were observed between the sacubitril/valsartan group and the medium- and high-dose HXWTF groups. ConclusionHXWTF may regulate the HIF-1α/TGF-β1/POSTN pathway to inhibit EndMT, thereby ameliorating post-MI ventricular remodeling.
7.A study on ethical issues and governance in health science popularization under the environment of four omni-media
Mingyue LI ; Qi LU ; Jianying MIN
Chinese Medical Ethics 2026;39(10):1410-1417
In the communication ecosystem of “four omni-media” (featuring omni-temporal media, omni-modal media, omni-participant media, and omni-effective media), the dissemination efficiency of health science popularization has been significantly enhanced. However, it simultaneously introduces numerous ethical issues, including information distortion and pseudoscience proliferation threatening the quality of popularization, data misuse and privacy breaches challenging information security, commercial conflicts of interest eroding public credibility, and information cocoon effects and audience cognitive biases undermining the effectiveness of popularization. To address these challenges, it is imperative to establish a systematic institutional guarantee framework and, through continuous technological innovation, to enhance capabilities in information auditing, algorithm optimization, and privacy protection. Concurrently, it is also vital to focus on establishing a professional talent pool and collaborative networks for health science popularization, optimizing the structure of funding allocation and resource distribution, and strengthening the ethical thinking and information literacy of both practitioners and the public. Ultimately, by constructing a new five-dimensional collaborative governance framework that synergizes “law, technology, organization, resources, and ethics”, we can promote the health science popularization cause in a more standardized, scientific, and ethical direction.
8.Mechanism of Intervening with Diarrhea-predominant Irritable Bowel Syndrome in Rats with Spleen Deficiency by Xingpi Capsules Through Regulating 5-HT-RhoA/ROCK2 Pathway
Gang WANG ; Lingwen CUI ; Xiangning LIU ; Rongxin ZHU ; Mingyue HUANG ; Ying SUN ; Boyang JIAO ; Ran WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):60-69
ObjectiveTo investigate the efficacy of Xingpi capsules (XPC) in treating diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free (SPF)-grade healthy rats were used as the normal control group. After successful modeling, SPF-grade rats were randomly divided into a model group, a pinaverium bromide group (1.5 mg·kg-1), and low- and high-dose XPC groups (0.135 and 0.54 g·kg-1), with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage, while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day, and the Bristol score was recorded. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 5-hydroxytryptamine (5-HT) in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier, intestinal motility, and expression of related pathway proteins were evaluated by hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot. ResultsCompared with those in the normal control group, rats in the model group showed a significantly decreased body weight and increased diarrhea rate, diarrhea grade, and Bristol score (P<0.01). HE staining revealed incomplete colonic mucosa in the model group, with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier, shedding and disappearance of microvilli, and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated (P<0.01), and the levels of 5-HT in serum and colon tissue were elevated (P<0.01). The small intestine propulsion rate significantly increased (P<0.01), and the expression of contractile proteins Ras homolog family member A (RhoA) and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) in colon and phosphorylation of myosin light chain (MLC20) were upregulated (P<0.01). Compared with the model group, the treatment groups showed alleviated diarrhea, diarrhea-associated symptoms, and pathological manifestations of colon tissue to varying degrees. Specifically, high-dose XPC exhibited effectively relieved diarrhea, promoted recovery of colonic mucosal structure, significantly reduced congestion and edema, upregulated expression of Occludin and Claudin-5 (P<0.01), decreased levels of 5-HT in serum and colon tissue (P<0.05,P<0.01), significantly slowed small intestine propulsion rate (P<0.01), and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC20 (P<0.05,P<0.01). ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction, and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.
9.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
10.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.


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