1.Protective Effect of Xuebijing on Lung Injury in Rats with Severe Acute Pancreatitis by Blocking FPRs/NLRP3 Inflammatory Pathway
Guixian ZHANG ; Dawei LIU ; Xia LI ; Xijing LI ; Pengcheng SHI ; Zhiqiao FENG ; Jun CAI ; Wenhui ZONG ; Xiumei ZHAO ; Hongbin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):113-120
ObjectiveTo explore the therapeutic effect of Xuebijing injection (XBJ) on severe acute pancreatitis induced acute lung injury (SAP-ALI) by regulating formyl peptide receptors (FPRs)/nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammatory pathway. MethodsSixty rats were randomly divided into a sham group, a SAP-ALI model group, low-, medium-, and high-dose XBJ groups (4, 8, and 12 mL·kg-1), and a positive drug (BOC2, 0.2 mg·kg-1) group. For the sham group, the pancreas of rats was only gently flipped after laparotomy, and then the abdomen was closed, while for the remaining five groups, SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate (Na-Tc) via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling, and the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) in plasma was measured by enzyme-linked immunosorbent assay (ELISA). The amount of ascites was measured, and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin (HE) staining to observe pathological changes and then scored. The protein expression levels of FPR1, FPR2, and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1, FPR2, and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of FPR1, FPR2, and NLRP3 in lung tissue. ResultsCompared with the sham group, the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue (P<0.01), serious pathological changes of lung tissue, a significantly increased pathological score (P<0.01), and significantly increased protein and mRNA expression levels of FPR1, FPR2, and NLRP3 in lung tissue (P<0.01). After BOC2 intervention, the above detection indicators were significantly reversed (P<0.01). After treatment with XBJ, the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue, which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.
2.Effect of GDF-15/GFRAL pathway on progression of atherosclerosis in mice
Hunan XIAO ; Benchuan HAO ; Lü LÜ ; Yulun CAI ; Xiaofan WANG ; Hongbin LIU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(9):1079-1083
Objective To investigate the effects and possible mechanisms of the growth differentia-tion factor 15(GDF-15)/glial-derived neurotrophic factor receptor alpha-like(GFRAL)pathway on the progression of atherosclerosis in ApoE-/-mice.Methods Eight 8-week-old male ApoE-/-mice were randomly divided into control group and rGDF-15 group.The mice in the control group received an injection of phosphate-buffered saline via tail vein once a week after 4 weeks of high-fat diet feeding,and those in the rGDF-15 group received an injection of recombinant GDF-15(0.05 mg/kg)via tail vein once a week after 4 weeks of high-fat diet feeding.The mice were fed with high-fat diet for another 8 weeks,the body weight was monitored during this period.After 12 weeks'feeding,the mice were euthanized.Another 4 normal mice(at the same age,20 weeks old)were subjected and served as normal control group.The levels of fasting blood glucose,blood lip-ids,cortisol,and aldosterone were compared among the three groups.Oil red O staining was used to evaluate plaque size in the aorta,and immunohistochemistry was employed to assess the expression of GDF-15 and GFRAL in the brain tissue.Results The serum level of GDF-15 was higher in the rGDF-15 group than in the control group(52.59±2.90 ng/ml vs 20.09±1.27 ng/ml,P<0.01).The weight of mice was significantly lower in the rGDF-15 group than the con-trol group during Week 11(28.60±0.22 g vs 29.47±0.25 g,P<0.01)and 12(28.98±0.22 g vs 30.35±0.13 g,P<0.01).The rGDF-15 group had a statistically lower level of triglycerides(0.22±0.02 mmol/L vs 0.38±0.09 mmol/L,P<0.05),lighter plaque burden[(22.22±2.58)%vs(31.61±3.51)%,P<0.01],and enhanced expression levels of GDF-15 and GFRAL in the brain tissue(0.088±0.007 vs 0.030±0.006,0.031±0.003 vs 0.010±0.001,P<0.01).The levels of cor-tisol and aldosterone in the control group and rGDF-15 group were significantly higher than those in the normal group(P<0.01).The aldosterone level in the rGDF-15 group was significantly re-duced compared to the control group(22.013.67 mg/ml vs 87.29±8.63 mg/ml,P<0.01).Conclusion GDF-15 may regulate body weight and triglyceride and aldosterone levels through GFRAL,and then affect the progression of atherosclerosis.
3.Screening and analysis of differentially expressed genes in basal cell carcino-ma of the eyelid
Jianwei YANG ; Lihua SONG ; Juan WANG ; Lulu ZHANG ; Li XIAO ; Hongbin ZHANG ; Limin LIU ; Yandong LIU
Recent Advances in Ophthalmology 2024;44(6):454-457
Objective To screen and analyze the differentially expressed genes(DEGs)in basal cell carcinoma(BCC)of the eyelid using RNA sequencing technology.Methods Six patients who underwent extended resection and primary eyelid reconstruction for BCC of the eyelid in Hebei Eye Hospital from July to November 2021 were selected.Part of the excised cancer tissues and the adjacent normal tissues trimmed during the repair of the defect were sampled for the study.The library construction for sequencing was performed using RNA sequencing technology.The threshold for DEGs was set using the DESeq2 software:P<0.05 and|log2(foldchange)|>1,to identify DEGs.Gene Ontology(GO)and Kyo-to Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using the clusterProfiler software,and the biological significance of these DEGs was further analyzed.Results DESeq2 software was used to analyze the differential expression between cancer tissues and adjacent tissues,and 1 317 DEGs were screened out.In the cancer tis-sues of the 6 patients,906 DEGs were up-regulated,and 411 DEGs were down-regulated.GO enrichment analysis showed that the top 30 up-regulated DEGs were mainly concentrated in humoral immune response,immunoglobulin complex,B cell receptor signaling pathway,extracellular matrix,antigen binding,and receptor modulator activity,and the top 10 down-regulated genes were mainly related to epidermal development in biological process,cell composition,and molecular func-tion.KEGG pathway analysis revealed that DEGs were mainly enriched in the melanogenesis signaling pathway,WNT sig-naling pathway,and immune-related signaling pathway,and there were 8 related gene pathways.According to the signifi-cance of gene up-regulation,the core genes identified finally were FZD2,PTCH1,WNT7B,TCF3,MMP-9,and TEAD2.Conclusion The occurrence of BCC is closely related to the interaction and synergy of various pathways.Among the highly expressed genes,the up-regulation of FZD2,PTCH1,WNT7B,TCF3,MMP-9,and TEAD2 expression in the tissues of patients with BCC of the eyelid is the most significant,which is closely related to the occurrence and development of BCC of the eyelid.
4.Mechanism study of BOC2 alleviating SAP inflammatory damage by inhibiting N-formyl peptide/formyl peptide receptor pathway
Guixian ZHANG ; Dawei LIU ; Wenchang LI ; Jun CAI ; Wenhui ZONG ; Hongbin LIU ; Xiumei ZHAO
Tianjin Medical Journal 2024;52(10):1031-1037
Objective To observe the effect of BOC-Phe-Leu-Phe-Leu-Phe(BOC2)on the expression of six types of mitochondrial N-formyl peptides(NFPs)in blood and two formyl peptide receptors(FPRs)in pancreatic tissue of rats with severe acute pancreatitis(SAP),and to explore its mechanism of alleviating inflammatory damage of SAP.Methods Forty male SD rats were randomly divided into four groups:the sham group,the SAP model group,the BOC2 low-dose and the BOC2 high-dose group(0.1 and 0.2 mg/kg),with 10 animals in each group.The SAP model was prepared by retrograde injection of 5%sodium taurocholate(50 mg/kg)into biliary and pancreatic ducts in the last 3 groups.BOC2 was intraperitoneally injected at 0.5 hours after SAP modeling,and samples were taken 4 hours after modeling.HE staining was used to observe pathological changes in pancreas.Western blot assay was used to detect the expression of NFPs in plasma.IHC staining was used to detect the expression of FPRs in pancreatic tissue.ELISA was used to detect interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α levels in plasma.qPCR was used to detect expression levels of inflammatory factors in local pancreatic tissue.Results Compared with the model group,the BOC2 high-dose group and the BOC2 low-dose group showed improvement in pathological phenomena,such as pancreatic bleeding,acinar cell necrosis,inflammatory cell infiltration and edema.The pancreatic injury score,pancreatic FPRs expression,plasma MT-ND1,MT-ND2,MT-ND3,MT-ND5,MT-ND6 expression,as well as expression levels of three inflammatory factors in plasma and local pancreatic tissue,were significantly reduced(P<0.05).Conclusion BOC2 can reduce the production of inflammatory factors and alleviate SAP inflammatory damage by antagonizing mitochondrial NFPs/FPRs signaling pathway.
5.Fluorescence and MR dual-mode imaging for displaying drainage pathways of interstitial fluid and substance clearance pattern in rat brain
Tianzi GAO ; Lan YUAN ; Yang WANG ; Hanbo TAN ; Ziyi WEI ; Jiayu WANG ; Yajuan GAO ; Dongyang LIU ; Cheng CUI ; Jianfei SUN ; Zhaoheng XIE ; Hongbin HAN
Chinese Journal of Medical Imaging Technology 2024;40(5):705-711
Objective To observe the drainage pathways of interstitial fluid(ISF)and substance clearance pattern in rat brain with fluorescence tracing imaging and treacer-based MRI.Methods Thirty-three male SD rats were randomly divided into fluorescence tracing group(F group,n=18)and treacer-based MRI group(MRI group,n=15),then further divided into thalamic,hippocampal and caudate nucleus subgroups,respectively.Evans blue was injected to rats in F group,and cardiac perfusion was performed after injection,then brain tissue was harvested,and frozen sections were made to observe the drainage pathways of IFS in different subgroups.MRI was performed on rats in MRI group before and after injection of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)to observe signal intensity in ROI of brain regions in different subgroups,the signal unit ratio was calculated,and the changing trend was explored.Results ISF in thalamus,hippocampus and caudate nucleus had different dominant drainage pathways,and the time of tracer reached to adjacent brain regions and whole brain in F group were different.In MRI group,within 4 h after injection of Gd-DTPA,there were differences in direction and clearance rate among tracer in thalamus,hippocampus and caudate nucleus,mainly manifesting as the tracer in thalamus and hippocampus drained to the ipsilateral cortex and lateral ventricle,while the tracer in the caudate nucleus diffused to the cortex and midbrain,and there were differences of the peak time of tracer signal among adjacent drainage brain regions.Conclusion Fluorescence and MR dual-mode imaging showed that there were differences in the dominant drainage pathways of IFS and clearance rates of small molecule substances among hypothalamus,hippocampus and caudate nucleus of rats.
6.Exploration of the regulatory mechanism of Danshen decoction on dyslipidemia in hyperlipidemia model rats based on proteomics
Yukun ZHANG ; Yuenan FENG ; Jingqi BIAN ; Xinxin LIU ; Hongbin XIAO ; Wenying NIU
China Pharmacy 2024;35(9):1070-1075
OBJECTIVE To explore the regulatory mechanism of Danshen decoction on dyslipidemia in hyperlipidemia model rats. METHODS The experimental rats were divided into blank group (n=9, no modeling), model group (n=8, modeling), and Danshen decoction group (n=9, modeling). Starting from the 9th week of feeding with the high-fat diet, rats in the Danshen decoction group were given the corresponding medication solution (3.6 g/kg) intragastrically, while blank group and model group were given equal volume of normal saline, once a day, for 4 consecutive weeks. After 4 weeks of administration, the plasma levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured in each group of rats; the pathological and morphological changes of liver tissue were observed; the differential proteins between samples were screened out by TMT quantitative proteomic analysis; the expression levels of the key differentially expressed proteins in the liver, including epoxide hydrolase 2 (EPHX2), perilipin 2 (PLIN2), peroxisome proliferator activated receptor γ (PPAR γ) and glycogen synthase kinase-3β (GSK-3β)were detected. RESULTS Compared with the model group, the plasma levels of TC, TG and LDL-C in the Danshen decoction group were significantly reduced (P<0.05), while the level of HDL-C was significantly increased (P<0.05). The liver tissue of rats inmodel group showed uneven staining, disordered arrangement of liver plates, disappearance of liver sinusoids, nuclearcondensation or disappearance of some cells, swelling and fusion of cytoplasm, proliferation of connective tissue, and diffuse vacuolar-like fat droplet changes. The liver tissue of Danshen decoction group showed varying degrees of improvement in the above pathological and morphological. The results of differential protein analysis showed that the total number of differential proteins was 298 between the model group and the blank group; the total number of differential proteins was 139 between the model group and Danshen decoction group. Compared with the model group, the expression levels of EPHX2 and PLIN2 proteins in the liver tissue of rats in the Danshen decoction group were significantly reduced (P<0.01), while the expression levels of GSK-3β and PPARγ were significantly increased (P<0.01). CONCLUSIONS Danshen decoction has a significant improvement effect on the plasma lipid levels and the pathological and morphological of the liver tissue in hyperlipidemia model rats. Its regulatory mechanism may be related to the up-regulation of PPARγ and GSK-3β expression and down-regulation of EPHX2 and PLIN2 expression, and the signaling pathways involved may include PPAR-γ signal pathway.
7.Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).
Qing ZHAO ; Tong WANG ; Hongbin WANG ; Peng CAO ; Chengyu JIANG ; Hongzhi QIAO ; Lihua PENG ; Xingdong LIN ; Yunyao JIANG ; Honglei JIN ; Huantian ZHANG ; Shengpeng WANG ; Yang WANG ; Ying WANG ; Xi CHEN ; Junbing FAN ; Bo LI ; Geng LI ; Bifeng LIU ; Zhiyang LI ; Suhua QI ; Mingzhen ZHANG ; Jianjian ZHENG ; Jiuyao ZHOU ; Lei ZHENG ; Kewei ZHAO
Chinese Herbal Medicines 2024;16(1):3-12
To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.
8.Mechanism of Danshenyin in Inhibiting Platelet Activation in Rat Model of Hyperlipidemia Based on Proteomics
Yukun ZHANG ; Yuenan FENG ; Jingqi BIAN ; Xinxin LIU ; Hongbin XIAO ; Wenying NIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):1-8
ObjectiveTo decipher the mechanism of Danshenyin in regulating platelet activation in the rat model of hyperlipidemia by means of proteomics and molecular biology. MethodWistar rats were randomized into blank, model, and Danshenyin groups (n=10) according to the blood lipid level. The rats in the blank group were fed with a basic diet, and those in the model and Danshenyin groups with a high-fat diet. All the rats had free access to water and food. The treatment began at the 9th week. The rats in the Danshenyin group were administrated with Danshenyin by gavage at a crude drug dose of 3.6 g·kg-1. The rats in the model and blank groups were administrated with an equal volume of normal saline according to body weight. At the 12th week, the tissue samples were collected for the measurement of related indicators, and the blood lipid level was measured by an automatic biochemical analyzer. The whole blood viscosity and plasma viscosity were measured by an automatic hemorheometer. The platelet proteome was determined by liquid chromatography-mass spectrometry. Western blotting was employed to determine the protein levels of platelet membrane glycoprotein 4 (CD36), focal adhesion kinase (FAK), phosphatidylinositol 4-phosphate 5-kinase (PIP5K), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), protein kinase B (Akt), and phosphorylated protein kinase B (p-Akt). ResultCompared with the model group, Danshenyin lowered the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in the plasma (P<0.05), elevated the level of high-density lipoprotein cholesterol (HDL-C) (P<0.05), and reduced the platelet aggregation rate (P<0.05). Compared with the blank group, the modeling up-regulated the expression of 44 proteins and down-regulated the expression of 12 proteins. Compared with the model group, Danshenyin up-regulated the expression of 21 proteins and down-regulated the expression of 22 proteins. Compared with the blank group, Danshenyin up-regulated the expression of 31 proteins and down-regulated the expression of 49 proteins. The gene ontology (GO) functional enrichment showed that the differentially expressed proteins were mainly involved in cholesterol transport and efflux, production of cytokines, dyslipidemia, and platelet activation. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment showed that the differentially expressed proteins were mainly involved in ECM-receptor interaction, peroxisome proliferators-activated receptors (PPAR), focal adhesion, and PI3K/Akt signaling pathways. Danshenyin can significantly down-regulate the expression of CD36, FAK, PIP5K, PI3K, p-Akt (Ser473), and p-Akt1/2/3 (Thr308). ConclusionDanshenyin can restore the blood lipid level of hyperlipidemia rats and inhibit the platelet activation caused by abnormal lipid levels by down-regulating the CD36/PI3K/Akt signal cascade.
9.Correlation between lower limb alignment and risk factors of patellofemoral pain syndrome in young men
Bing HAN ; Hongbin LIU ; Hehong WANG ; Hanqing ZHAO ; Riguang ZHAO ; Yiyan SUN ; Yu ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(8):1211-1216
BACKGROUND:The risk factors for patellofemoral pain syndrome are still unclear and research on risk factors is gradually becoming a hot topic in order to improve the therapeutic outcome of this disease. OBJECTIVE:To investigate the relationship between lower limb alignment and patellofemoral pain syndrome in young male runners. METHODS:In the same running population,21 patients with bilateral knee pain,29 patients with single knee pain and 20 normal runners were collected from January 2021 to July 2022.Full-length X-ray examination of both lower limbs in standing position was performed in all subjects.The lateral distal femoral angle,medial tibial proximal angle,joint line congruence angle,hip-knee-ankle angle,and knee physical valgus angle were measured and statistically analyzed. RESULTS AND CONCLUSION:There was no significant difference in the parameters between the left and right knees in each group(P>0.05).Compared with the normal group,no significant changes in lateral distal femoral angle,medial tibial proximal angle,joint line congruence angle,and hip-knee-ankle angle were observed in the single knee pain group and double knee pain group,while the knee physical valgus angle was significantly increased in these two groups(P<0.05).To conclude,increased knee physical valgus angle may be a risk factor for patellofemoral pain syndrome.
10.Colorectal polyp segmentation algorithm integrating Transformer and convolution
Chinese Journal of Medical Physics 2024;41(3):316-322
In response to the challenges of varied sizes and diverse shapes of colorectal polyps,especially with blurred boundaries that often complicates localization and smaller polyps being particularly prone to oversight,a colorectal polyp segmentation algorithm integrating Transformer and convolution is proposed.Transformer is employed to extract global features from images for ensuring the network's capability for global modeling and improving the localization capability for both main polyp regions and vague boundaries.Subsequently,convolution is introduced to augment the network's ability to process polyp details,refining boundary segmentation and enhancing the capture capability for small-sized polyps.Finally,a deep fusion of the features extracted by Transformer and convolution is carried out to realize feature complementarity.The experimental evaluation using CVC-ClinicDB and Kvasir-SEG datasets show that the algorithm has similarity coefficients of 95.4%and 93.2%,and mean intersection over union of 91.3%and 88.6%,respectively.Further tests on the generalization capability of the algorithm are conducted on CVC-ColonDB,CVC-T,and ETIS datasets,in which similarity coefficients of 81.3%,90.9%and 80.1%are obtained.The results indicate a notable improvement in the accuracy of polyp segmentation achieved by the proposed algorithm.

Result Analysis
Print
Save
E-mail