1.Factors affecting implementation of weight management services in primary medical and healthcare institutions based on the consolidated framework for implementation research
SUN Jie ; LI Yun ; WEI Jiayu ; SHAO Xiaofang ; YE Xiaojun ; FU Yeliu ; GU Wei ; YANG Min
Journal of Preventive Medicine 2025;37(11):1087-1092
Objective:
To explore the influencing factors for implementation of weight management services in primary medical and healthcare institutions, so as to provide references for implementing sustainable services of weight management.
Methods:
From May to June 2025, Pinghu City, Zhejiang Province was selected as the survey site. Personnel responsible for weight management in primary medical and healthcare institutions were selected as the survey subjects using a combined method of purposive sampling and snowball sampling. Based on the five core domains of the consolidated framework for implementation research (CFIR), a semi-structured interview outline for weight management services in primary medical and healthcare institutions was designed. Original data was collected through face-to-face semi-structured interviews. Interview data was organized and analyzed using framework analysis. Factors affecting weight management services were quantitatively analyzed by referencing CFIR's structural rating criteria.
Results:
A total of 21 participants completed interviews, covering positions in nutrition, endocrinology, traditional Chinese medicine, general practice, maternal health, and public health. There were 9 males and 12 females. Fifteen participants (71.43%) were aged 35 years and above, 18 (85.71%) held a bachelor's degree or higher, and 15 (71.43%) were frontline medical staff. Fifteen factors affecting weight management services were identified across five domains: innovation, outer setting, inner setting, individuals, and implementation process. Six barrier factors were identified: difficulties in policy implementation, time-consuming interventions, limited incentive measures, lack of professional skills, unclear weight-loss plans and goal setting, and imperfect follow-up and evaluation mechanisms. Three neutral factors were identified: the development and refinement of policies and regulations, the implementation of weight management training, and the optimization of the referral process within integrated healthcare systems (medical alliances / communities). Six facilitating factors were identified: the relatively significant advantages of lifestyle interventions, collaboration and coordination across multiple departments, cooperative communication among different units within the institution, the inherent convenience of primary care settings, a strong sense of professional responsibility, and the establishment of multidisciplinary teams.
Conclusions
The delivery of weight management services in primary medical and healthcare institutions is influenced by a wide array of factors across multiple domains. It requires policy support, multi-department coordination, a practice-oriented training system, optimized team resource allocation, incentives, and improved professional skills of medical staff to jointly promote long-term implementation.
2.Agitation of TGR5 by INT-777 protected hypoxic-ischemic encephalopathy in neonatal rats
Rong-jie LIU ; Qin CHEN ; Ying XIONG ; Zhao-yun WANG ; Chang-ling CHEN ; Qin ZHANG ; Mao-qiong CHEN ; Zhan-hui FENG ; Lan YE
Chinese Pharmacological Bulletin 2025;41(6):1085-1090
Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.
3.Mechanism of Polygonum capitatum on atherosclerosis based on data mining
Zi YE ; Yun-pei WANG ; Yu-hui WANG ; Xun-de XIAN ; Xiao-jie LI ; Chun-hua HUANG ; Yuan-zhu LIAO ; Di-dong LOU ; Yi-xia ZHOU
Chinese Pharmacological Bulletin 2025;41(12):2369-2378
Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.
4.Effect of IDream reconstruction technique based on iterative reconstruction algorithm on image quality of low-dose CT on upper abdomen and the displays of hepatic cyst
Peng YE ; Huayang DU ; Zhengjun LI ; Man WANG ; Yun WANG ; Yukun LIANG ; Jie FANG
China Medical Equipment 2025;22(1):13-18
Objective:To investigate the optimal reconstruction grade of IDream reconstruction technique in reducing image noise,optimizing image quality,and displaying liver cysts through the subjective assessment on the display of computed tomography (CT) image with differently reconstructive grades in IDream reconstruction technique of iterative reconstruction algorithm,and the objective evaluation of image quality of upper abdomen. Methods:The imaging data of CT plain scan of 53 patients with hepatic cysts who underwent plain scans on upper abdomen at Peking Union Medical College Hospital from August to September 2021 were retrospectively collected. All images were reconstructed to standard window images by using 6 kinds of methods that included filtered back projection (FBP) and IDream grades 1 to 5,which resulted in 6 groups of images that included FBP group and IDream grades 1-5. The CT values and standard deviation (SD) values of the liver,abdominal aorta,erector spine muscle,fat and spleen in images of each group were measured and recorded,respectively. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images were calculated. Two CT diagnostic physicians with more than 8 years of experience conducted subjective scoring for the display in the images of hepatic cysts of each group. The objective parameters and the subjective scores of hepatic cysts of reconstructive images with different grades were compared. A one-way analysis of variance was adopted to analyze the objective parameters,and Kruskal-Wallis H test was conducted on the subjective score of the display of hepatic cysts. Results:There were no statistically significant differences in the CT values among different reconstruction grades on the liver,abdominal aorta,fat,erector spine muscle and spleen (P>0.05). In the FBP group and IDream grades 1 to 5 groups,the SD values of images gradually decreased with the increasing of the reconstruction grades,which were respectively (18.11±5.03),(15.37±4.97),(13.26±4.83),(11.68±4.56),(10.99±4.36) and (10.60±4.21) Hu. The SNR and CNR of the liver gradually increased. The differences in SD values,SNR,and CNR among the six groups of images were all statistically significant (F=20.75,17.72,3.15,P<0.05),respectively. The subjective scores for the display of hepatic cysts from the FBP group to IDream grades 1 to 4 were respectively (3.12±0.35),(3.63±0.46),(4.02±0.42),(4.61±0.48) and (4.63±0.48),which were gradually increasing,while the score for the IDream grade 5 group slightly decreased to (4.53±0.47). The subjective scores for hepatic cysts in the images of IDream grades 3 and 4 groups were the highest. The comparison of the average subjective scores of the images of hepatic cysts among the six reconstruction grades showed statistically significant differences (H=192.17,P<0.05). Conclusion:In CT plain scan on the upper abdomen,with the increasing of IDream reconstruction grades,the image noises gradually decrease,and objective parameters of images gradually enhance,and the reconstructions of IDream grades 3 and 4 can obtain the optimal image quality of upper abdomen at the objective score of hepatic cysts.
5.Role of SWI/SNF Chromatin Remodeling Complex in Tumor Drug Resistance
Gui-Zhen ZHU ; Qiao YE ; Yuan LUO ; Jie PENG ; Lu WANG ; Zhao-Ting YANG ; Feng-Sen DUAN ; Bing-Qian GUO ; Zhu-Song MEI ; Guang-Yun WANG
Progress in Biochemistry and Biophysics 2025;52(1):20-31
Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca2+ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca2+ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.
6.Mechanism of Yishen Jiangtang Decoction in regulating endoplasmic reticulum stress-mediated NLRP3 inflammasome to improve renal damage in diabetic nephropathy db/db mice.
Yun-Jie YANG ; Bin-Hua YE ; Chen QIU ; Han-Qing WU ; Bo-Wei HUANG ; Tong WANG ; Shi-Wei RUAN ; Fang GUO ; Jian-Ting WANG ; Ming-Qian JIANG
China Journal of Chinese Materia Medica 2025;50(10):2740-2749
This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals
;
Endoplasmic Reticulum Stress/drug effects*
;
Diabetic Nephropathies/metabolism*
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
Drugs, Chinese Herbal/administration & dosage*
;
Mice
;
Inflammasomes/drug effects*
;
Male
;
Kidney/pathology*
;
Endoplasmic Reticulum Chaperone BiP
;
Humans
;
Interleukin-18/genetics*
;
Mice, Inbred C57BL
7.Effect of IDream reconstruction technique based on iterative reconstruction algorithm on image quality of low-dose CT on upper abdomen and the displays of hepatic cyst
Peng YE ; Huayang DU ; Zhengjun LI ; Man WANG ; Yun WANG ; Yukun LIANG ; Jie FANG
China Medical Equipment 2025;22(1):13-18
Objective:To investigate the optimal reconstruction grade of IDream reconstruction technique in reducing image noise,optimizing image quality,and displaying liver cysts through the subjective assessment on the display of computed tomography (CT) image with differently reconstructive grades in IDream reconstruction technique of iterative reconstruction algorithm,and the objective evaluation of image quality of upper abdomen. Methods:The imaging data of CT plain scan of 53 patients with hepatic cysts who underwent plain scans on upper abdomen at Peking Union Medical College Hospital from August to September 2021 were retrospectively collected. All images were reconstructed to standard window images by using 6 kinds of methods that included filtered back projection (FBP) and IDream grades 1 to 5,which resulted in 6 groups of images that included FBP group and IDream grades 1-5. The CT values and standard deviation (SD) values of the liver,abdominal aorta,erector spine muscle,fat and spleen in images of each group were measured and recorded,respectively. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the images were calculated. Two CT diagnostic physicians with more than 8 years of experience conducted subjective scoring for the display in the images of hepatic cysts of each group. The objective parameters and the subjective scores of hepatic cysts of reconstructive images with different grades were compared. A one-way analysis of variance was adopted to analyze the objective parameters,and Kruskal-Wallis H test was conducted on the subjective score of the display of hepatic cysts. Results:There were no statistically significant differences in the CT values among different reconstruction grades on the liver,abdominal aorta,fat,erector spine muscle and spleen (P>0.05). In the FBP group and IDream grades 1 to 5 groups,the SD values of images gradually decreased with the increasing of the reconstruction grades,which were respectively (18.11±5.03),(15.37±4.97),(13.26±4.83),(11.68±4.56),(10.99±4.36) and (10.60±4.21) Hu. The SNR and CNR of the liver gradually increased. The differences in SD values,SNR,and CNR among the six groups of images were all statistically significant (F=20.75,17.72,3.15,P<0.05),respectively. The subjective scores for the display of hepatic cysts from the FBP group to IDream grades 1 to 4 were respectively (3.12±0.35),(3.63±0.46),(4.02±0.42),(4.61±0.48) and (4.63±0.48),which were gradually increasing,while the score for the IDream grade 5 group slightly decreased to (4.53±0.47). The subjective scores for hepatic cysts in the images of IDream grades 3 and 4 groups were the highest. The comparison of the average subjective scores of the images of hepatic cysts among the six reconstruction grades showed statistically significant differences (H=192.17,P<0.05). Conclusion:In CT plain scan on the upper abdomen,with the increasing of IDream reconstruction grades,the image noises gradually decrease,and objective parameters of images gradually enhance,and the reconstructions of IDream grades 3 and 4 can obtain the optimal image quality of upper abdomen at the objective score of hepatic cysts.
8.Current situation of interventional nursing research in China based on Chinese Clinical Trial Registry
Jie DU ; Xiaobao LI ; Yun YE
Journal of Clinical Medicine in Practice 2025;29(12):125-129
Objective To analyze the current status of interventional nursing studies registered in the Chinese Clinical Trial Registry(ChiCTR).Methods All intervention nursing studies registered in the ChiCTR self-establishment database from May 31,2024 were retrieved,and relevant information of the registered studies was included and extracted.Results A total of 462 nursing intervention stud-ies were included,among which 365 were pre-registered and 97 were supplementary registered.The number of registered items in 2020 and beyond accounted for 83.33%of the total number of registra-tions.Currently,the top three regions in terms of the number of registrations were Shanghai(56 items),Guangdong Province(50 items)and Beijing(49 items).A total of 12 units had registration number of ≥5,among which West China Hospital of Sichuan University had 18 registrations.Among all the projects,160 were self-funded(34.63%),and 48 were multi-center cooperative research(10.39%).There were 322 randomized parallel controlled trials,among which 281(87.27%)pro-vided further descriptions of randomization and 167(51.86%)provided further descriptions of blind-ing.The registered items for the research subjects of nursing staff were 94,mainly concentrated in the research fields such as nursing teaching,mental health,job burnout,stress and sleep.There were 368 registered items whose research subjects were patients or clinical problems,mainly concentrated in re-search fields such as rehabilitation nursing,quality of life,self-management and nutrition management.Conclusion The number of registrations of interventional nursing research in China on the ChiCTR platform has been increasing year by year.However,the registration regions and the distribution of funds are uneven,and the number of cooperative projects is relatively small,which is not conducive to the integration and exertion of multidisciplinary advantages.In addition,the application of ran-domization and blinding is not standardized,the registration information is incomplete,and the core research hotspots need to be further expanded and improved.It is suggested to start from aspects such as organizing registration training and strengthening the training of nursing research design to further improve the level of nursing scientific research.
9.Agitation of TGR5 by INT-777 protected hypoxic-ischemic encephalopathy in neonatal rats
Rong-jie LIU ; Qin CHEN ; Ying XIONG ; Zhao-yun WANG ; Chang-ling CHEN ; Qin ZHANG ; Mao-qiong CHEN ; Zhan-hui FENG ; Lan YE
Chinese Pharmacological Bulletin 2025;41(6):1085-1090
Aim To investigate the neuroprotective effect of Takeda G protein-coupled receptor-5(TGR5)activated by INT-777 on hypoxic-ischemic encephalop-athy(HIE)in neonatal rats.Methods Seven-day-old SD rats were randomly divided into the sham opera-tion group(Sham,S),model group(HIE,G),INT-777 low-dose(L),medium-dose(M),and high-dose(H)groups.The modified Rice-Vanucci method was used to construct the HIE model and Intranasal admin-istration 1 h after modeling.Short-term neurobehavioral tests were performed 48 h after modeling to evaluate the neurological function of neonatal rats,TTC staining was used to determine the volume of cerebral infarction,dry and wet specific gravity was used to determine the brain water content,ferrous ion kit was used to deter-mine the brain ferrous ion content,HE staining was used to observe the pathological damage of brain tis-sue,Nissl staining was used to observe the loss of Nissl substance,Transmission electron microscopy(TEM)was used to observe the mitochondrial morphological changes of cortical neurons,and Western blot was em-ployed to detect the expression of ferroptosis-related proteins TFR1 and GPX4.Results Compared with group S,group G had increased short-term neurobehav-ioral test consumption time,higher scores,increased cerebral infarct volume,brain water content,and brain ferrous iron content,significant brain tissue damage on the affected side,severe loss of Nissl substance,smaller neuronal mitochondria,decreased mitochondrial cris-tae,and increased expression of TFR1 and reduced ex-pression of GPX4.Compared with group G,the INT-777 administration group had a shorter consumption time for short-term neurobehavioral tests,lower scores,the cerebral infarction volume,brain water content,and brain ferrous ion content decreased,the brain tissue damage on the affected side was reduced,and there was insignificant loss of Nissl substance,larger neuronal mi-tochondrial volume,increased mitochondrial cristae,re-duced expression of TFR1,and increased expression of GPX4.Conclusions INT-777 agonist TGR5 has a protective effect against hypoxic-ischemic encephalopa-thy in neonatal rats,and its mechanism of action may be related to the inhibition of neuronal ferroptosis.
10.Mechanism of Polygonum capitatum on atherosclerosis based on data mining
Zi YE ; Yun-pei WANG ; Yu-hui WANG ; Xun-de XIAN ; Xiao-jie LI ; Chun-hua HUANG ; Yuan-zhu LIAO ; Di-dong LOU ; Yi-xia ZHOU
Chinese Pharmacological Bulletin 2025;41(12):2369-2378
Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.


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