1.DHLX studied correlation between regulation of biliary flora and inflammatory factors on gallbladder stone formation
Yirong GAN ; Yuan YU ; Jinmei CHEN ; Chengji LI ; Wen YANG ; Jiaoan PANG ; Chunli LIU ; Lijun XIAO ; Jinhao TENG
Chinese Journal of Immunology 2025;41(3):644-649
Objective:By sequencing and analyzing the biliary flora by 16S rDNA high-throughput sequencing technology,to identify the main flora associated with gallbladder stone formation and the main flora regulated by the Dahuang lingxian(DHLX),pre-liminary investigation the effect of DHLX on the biliary flora.Methods:The 50 male guinea pigs were randomly divided into Normal group,Model group,DHLX group.There were 15 guinea pigs in the normal group and 20 guinea pigs in the DHLX group,and 20 guin-ea pigs in the model group:the guinea pig model of gallstone was replicated with high-fat lithogenic diet,which was simultaneously ad-ministrated by gavage.After continuous intervention for 8 weeks,bile and gallbladder tissue samples were collected,and the gallstone formation rate of guinea pigs in each group was calculated,the pathological morphological changes of gallbladder tissue were detected by HE,T-CHO,TBA,LPS,IL-6,TNF-α were detected by ELISA,and the changes of biliary flora were detected by 16S rDNA;the correlation between biliary flora and bile index was detected by Pearson statistical method.Results:The stone formation rate of guinea pigs in the normal group was 8.3%,the rate of model stone composition was 90.8%,and the stone composition rate of DHLX group was 36.4%,and the HE staining results showed that compared with the normal group,the mucous membrane of the guinea pig in the model group was thickened,the columnar epithelial cells were arranged in a large number of inflammatory cells,and the columnar epi-thelial cells of the gallbladder mucosa in the chinese medicine group were arranged neatly compared with the model group,the thick-ness of the mucosa was reduced compared with the model group,and some inflammatory cells were infiltrated;ELISA results showed that compared with the normal group,the expressions of T-CHO,LPS,IL-6 and TNF-α in the bile of guinea pigs in the model group were significantly increased(P<0.01),while the content of TBA was significantly reduced(P<0.01);compared with the model group,the expression of LPS and IL-6 in the bile of the DHLX group were significantly reduced(P<0.01).The results of 16S rDNA showed that compared with the normal group the Ace index and Chao1 index of the model group were significantly reduced(P<0.01),and the Chao1 index of the DHLX group was significantly higher than that of the model group(P<0.05);biliary flora at the genera level was mainly composed of Burkholderia,Sphingomycetes,Breghamus,Delfortella,Pseudomonas;correlation analysis showed that total cholesterol was negatively correlated with the abundance of Methyloversatilis(P<0.05),and total bile acids were positively corre-lated with the abundance of Burkholderia(P<0.05),and Pseudomonas erythrocytes,Rhizobia,the abundance of Phreatobacter was negatively correlated(P<0.01)and LPS was positively correlated with the abundance of Pseudomonas erythrocytes(P<0.01).Conclu-sion:Biliary microflora disorder exists in the formation of biliary stones,and biliary microflora may participate in the formation of stones by regulating cholesterol,bile acids and LPS.DHLX can regulate the changes in the abundance of the microflora,make the structure of the microflora become normal,reduce the inflammation of the gallbladder,and prevent the formation of gallstones.
2.DHLX studied correlation between regulation of biliary flora and inflammatory factors on gallbladder stone formation
Yirong GAN ; Yuan YU ; Jinmei CHEN ; Chengji LI ; Wen YANG ; Jiaoan PANG ; Chunli LIU ; Lijun XIAO ; Jinhao TENG
Chinese Journal of Immunology 2025;41(3):644-649
Objective:By sequencing and analyzing the biliary flora by 16S rDNA high-throughput sequencing technology,to identify the main flora associated with gallbladder stone formation and the main flora regulated by the Dahuang lingxian(DHLX),pre-liminary investigation the effect of DHLX on the biliary flora.Methods:The 50 male guinea pigs were randomly divided into Normal group,Model group,DHLX group.There were 15 guinea pigs in the normal group and 20 guinea pigs in the DHLX group,and 20 guin-ea pigs in the model group:the guinea pig model of gallstone was replicated with high-fat lithogenic diet,which was simultaneously ad-ministrated by gavage.After continuous intervention for 8 weeks,bile and gallbladder tissue samples were collected,and the gallstone formation rate of guinea pigs in each group was calculated,the pathological morphological changes of gallbladder tissue were detected by HE,T-CHO,TBA,LPS,IL-6,TNF-α were detected by ELISA,and the changes of biliary flora were detected by 16S rDNA;the correlation between biliary flora and bile index was detected by Pearson statistical method.Results:The stone formation rate of guinea pigs in the normal group was 8.3%,the rate of model stone composition was 90.8%,and the stone composition rate of DHLX group was 36.4%,and the HE staining results showed that compared with the normal group,the mucous membrane of the guinea pig in the model group was thickened,the columnar epithelial cells were arranged in a large number of inflammatory cells,and the columnar epi-thelial cells of the gallbladder mucosa in the chinese medicine group were arranged neatly compared with the model group,the thick-ness of the mucosa was reduced compared with the model group,and some inflammatory cells were infiltrated;ELISA results showed that compared with the normal group,the expressions of T-CHO,LPS,IL-6 and TNF-α in the bile of guinea pigs in the model group were significantly increased(P<0.01),while the content of TBA was significantly reduced(P<0.01);compared with the model group,the expression of LPS and IL-6 in the bile of the DHLX group were significantly reduced(P<0.01).The results of 16S rDNA showed that compared with the normal group the Ace index and Chao1 index of the model group were significantly reduced(P<0.01),and the Chao1 index of the DHLX group was significantly higher than that of the model group(P<0.05);biliary flora at the genera level was mainly composed of Burkholderia,Sphingomycetes,Breghamus,Delfortella,Pseudomonas;correlation analysis showed that total cholesterol was negatively correlated with the abundance of Methyloversatilis(P<0.05),and total bile acids were positively corre-lated with the abundance of Burkholderia(P<0.05),and Pseudomonas erythrocytes,Rhizobia,the abundance of Phreatobacter was negatively correlated(P<0.01)and LPS was positively correlated with the abundance of Pseudomonas erythrocytes(P<0.01).Conclu-sion:Biliary microflora disorder exists in the formation of biliary stones,and biliary microflora may participate in the formation of stones by regulating cholesterol,bile acids and LPS.DHLX can regulate the changes in the abundance of the microflora,make the structure of the microflora become normal,reduce the inflammation of the gallbladder,and prevent the formation of gallstones.
3.Qihuang Jianpi Zishen Granules improves thrombocytopenia in mice with systemic lupus erythematosus by suppressing platelet autophagy via the Ca2+/CaMKK2/AMPK/mTOR signaling pathway.
Yunfei LI ; Lijun PANG ; Longwu SHU ; Ming LI ; Chuanbing HUANG
Journal of Southern Medical University 2024;44(12):2327-2334
OBJECTIVES:
To explore the mechanism of Qihuang Jianpi Zishen Granules (QJZG) for improving thrombocytopenia in a mouse model of systemic lupus erythematosus (SLE).
METHODS:
Twenty-four MRL/lpr lupus mice were randomized equally into 4 groups for treatment with daily gavage of saline, QJZG or prednisone (Pred) or intraperitoneal injection (twice a week) of CaMKK2 activator, with 6 C57BL/6 mice with saline gavage as the control group. After 8 weeks of treatment, the mice were examined for PLT, PCT, PDW, MPV, serum levels of TPO, IL-6, IL-10, TNF-α and IFN-γ, and calcium ion fluorescence intensity using ELISA or flow-through assay. RT-qPCR was used to detect platelet CaMKK2, AMPK2α, mTOR, Beclin1 and p62 mRNA expression levels, and the protein expressions of CaMKK2, p-CaMKK2, AMPK, p-AMPK, mTOR, p-mTOR, LC3, Beclin1 and p62 were detected using Western blotting.
RESULTS:
The saline-treated MRL/lpr lupus mice showed significantly lowered levels of PLT, PCT, IL-10, mTOR, p62 mRNA, p-mTOR and P62 with increased PDW, MPV, serum TPO, IL-6, TNF-α and IFN-γ levels, and platelet expressions of CaMKK2, AMPK, Bcl-1 mRNA, p-CaMKK2, p-AMPK, LC3II and Beclin1. These abnormalities were significantly improved in QJZG group and Pred group but worsened after treatment with the CaMKK2 activator.
CONCLUSIONS
QJZG can ameliorate thrombocytopenia in mouse models of SLE by reducing inflammation and inhibiting platelet autophagy via regulating the Ca2+/CaMKK2/AMPK/mTOR signaling pathways.
Animals
;
Lupus Erythematosus, Systemic/metabolism*
;
Mice
;
Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism*
;
Drugs, Chinese Herbal/pharmacology*
;
TOR Serine-Threonine Kinases/metabolism*
;
Thrombocytopenia/metabolism*
;
Signal Transduction/drug effects*
;
Autophagy/drug effects*
;
AMP-Activated Protein Kinases/metabolism*
;
Disease Models, Animal
;
Mice, Inbred C57BL
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Mice, Inbred MRL lpr
;
Calcium/blood*
;
Blood Platelets/metabolism*
4.Qihuang Jianpi Zishen Granules improves thrombocytopenia in mice with systemic lupus erythematosus by suppressing platelet autophagy via the Ca2+/CaMKK2/AMPK/mTOR signaling pathway
Yunfei LI ; Lijun PANG ; Longwu SHU ; Ming LI ; Chuanbing HUANG
Journal of Southern Medical University 2024;44(12):2327-2334
Objective To explore the mechanism of Qihuang Jianpi Zishen Granules(QJZG)for improving thrombocytopenia in a mouse model of systemic lupus erythematosus(SLE).Methods Twenty-four MRL/lpr lupus mice were randomized equally into 4 groups for treatment with daily gavage of saline,QJZG or prednisone(Pred)or intraperitoneal injection(twice a week)of CaMKK2 activator,with 6 C57BL/6 mice with saline gavage as the control group.After 8 weeks of treatment,the mice were examined for PLT,PCT,PDW,MPV,serum levels of TPO,IL-6,IL-10,TNF-α and IFN-γ,and calcium ion fluorescence intensity using ELISA or flow-through assay.RT-qPCR was used to detect platelet CaMKK2,AMPK2α,mTOR,Beclin1 and p62 mRNA expression levels,and the protein expressions of CaMKK2,p-CaMKK2,AMPK,p-AMPK,mTOR,p-mTOR,LC3,Beclin1 and p62 were detected using Western blotting.Results The saline-treated MRL/lpr lupus mice showed significantly lowered levels of PLT,PCT,IL-10,mTOR,p62 mRNA,p-mTOR and P62 with increased PDW,MPV,serum TPO,IL-6,TNF-α and IFN-γ levels,and platelet expressions of CaMKK2,AMPK,Bcl-1 mRNA,p-CaMKK2,p-AMPK,LC3Ⅱ and Beclin1.These abnormalities were significantly improved in QJZG group and Pred group but worsened after treatment with the CaMKK2 activator.Conclusion QJZG can ameliorate thrombocytopenia in mouse models of SLE by reducing inflammation and inhibiting platelet autophagy via regulating the Ca2+/CaMKK2/AMPK/mTOR signaling pathways.
5.Construction of a Quality Control System for Oncology Medical Records Based on Natural Language Processing
Weiwei LIU ; Lijun WANG ; Juan PANG ; Dan WANG ; Fanxiu HENG
Journal of Medical Informatics 2024;45(2):77-81,91
Purpose/Significance Through the establishment of a quality control system for electronic medical record(EMR)con-tent,the standardization and normalization of medical record writing is realized,and the quality of hospital medical record is improved.Method/Process The intelligent medical data center is built based on hospital medical data,and the knowledge base and rule base with tumor specialty characteristics are formed by combining natural language processing(NLP)and machine learning technology.The new quality control mode of"pre-audit,comprehensive coverage,process supervision and closed-loop management"of EMR is realized.Result/Conclusion After the application of the medical record quality control system based on NLP,the quality control coverage rate in-creased from 1%to 100%,and the rate of class A medical records increased to more than 96%,with good real-time and accuracy,providing a solid information foundation for the high-quality development of hospital medical records.
6.An attention-guided network for bilateral ventricular segmentation in pediatric echocardiography.
Jun PANG ; Yongxiong WANG ; Lijun CHEN ; Jiapeng ZHANG ; Jinlong LIU ; Gang PEI
Journal of Biomedical Engineering 2023;40(5):928-937
Accurate segmentation of pediatric echocardiograms is a challenging task, because significant heart-size changes with age and faster heart rate lead to more blurred boundaries on cardiac ultrasound images compared with adults. To address these problems, a dual decoder network model combining channel attention and scale attention is proposed in this paper. Firstly, an attention-guided decoder with deep supervision strategy is used to obtain attention maps for the ventricular regions. Then, the generated ventricular attention is fed back to multiple layers of the network through skip connections to adjust the feature weights generated by the encoder and highlight the left and right ventricular areas. Finally, a scale attention module and a channel attention module are utilized to enhance the edge features of the left and right ventricles. The experimental results demonstrate that the proposed method in this paper achieves an average Dice coefficient of 90.63% in acquired bilateral ventricular segmentation dataset, which is better than some conventional and state-of-the-art methods in the field of medical image segmentation. More importantly, the method has a more accurate effect in segmenting the edge of the ventricle. The results of this paper can provide a new solution for pediatric echocardiographic bilateral ventricular segmentation and subsequent auxiliary diagnosis of congenital heart disease.
Adult
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Humans
;
Child
;
Heart Ventricles/diagnostic imaging*
;
Echocardiography
;
Image Processing, Computer-Assisted
7.Clinical Efficacy of Qihuang Jianpi Zishen Granules in Treating Cardiac Involvement in Systemic Lupus Erythematosus
Yunfei LI ; Lijun PANG ; Longwu SHU ; Wanlan FU ; Shuangshuang SHANG ; Ming LI ; Chuanbing HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):104-111
ObjectiveTo investigate the clinical efficacy and safety of Qihuang Jianpi Zishen granules in the treatment of cardiac involvement in systemic lupus erythematosus (SLE). MethodA total of 62 SLE patients with cardiac involvement treated in the Department of Rheumatology and Immunology, the First Affiliated Hospital of Anhui University of Chinese Medicine from June 2021 to December 2022 were randomized into control and observation groups (n=31). The control group was treated with methylprednisolone tablets and hydroxychloroquine sulfate tablets, and the observation group with Qihuang Jianpi Zishen granules on the basis of the therapy in the control group. After 12 weeks of treatment, the two groups were compared in terms of the therapeutic effect, cardiac function indicators [left atrial end-diastolic diameter (LADd), left ventricular end-diastolic diameter (LVDd), left ventricular posterior wall thickness (LVPWTd), peak blood flow velocity in early diastolic period (peak E), peak blood flow velocity in late diastolic period (peak A), E/A ratio, stroke volume (SV), left ventricular ejection fraction (LVEF), left ventricular short axis shortening rate (LVFS), and B-type natriuretic peptide (BNP)], vascular damage indicators [nitric oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and homocysteine (Hcy)], inflammation indicators [erythrocyte sedimentation rate (ESR) and hypersensitive C-reactive protein (Hs-CRP)], anti-double-stranded DNA (dsDNA) antibodies, disease activity index (SLEDAI) score, mitigation of symptoms and signs, and occurrence of adverse reactions. ResultThe total response rate in the observation group was 87.09%, which was higher than that (67.74%) in the control group (P<0.01), and the incidence of adverse reactions had no significant difference between the two groups. After treatment, the control group showed lowered LVDd, LVPWTd, BNP, ET-1, VEGF, and Hcy (P<0.05) and increased E peak, E/A ratio, SV, LVEF, and LVFS (P<0.05). In the observation group, LADd, LVDd, LVPWTd, peak A, BNP, NO, ET-1, VEGF, and Hcy decreased (P<0.05), while peak E, E/A ratio, SV, LVEF and LVFS increased (P<0.05) after treatment. The treatment in both groups decreased the scores of palpitation, chest tightness, dyspnea, and edema (P<0.05), reduced ESR, Hs-CRP, ds-DNA, and SLEDAI (P<0.05). After treatment, the observation group had lower LADd, LVDd, LVPWTd, peak A, BNP, and scores of palpation, chest tightness, dyspnea, and edema (P<0.05) and higher peak E, E/A ratio, SV, LVEF, and LVFS (P<0.05) than the control group. In addition, the observation group had lower NO, ET-1, VEGF, Hcy, ESR, Hs-CRP, ds-DNA, and SLEDAI than the control group (P<0.05). ConclusionQihuang Jianpi Zishen granules combined with hydroxychloroquine sulfate and methylprednisolone can improve multiple indicators and mitigate the symptoms and signs of SLE patients with cardiac involvement, demonstrating a clinical application value.
8.Effect of Dahuang Lingxian prescription on the scf/c-kit signaling pathway in gallbladder interstitial cells of Cajal in a guinea pig model of cholesterol gallstone
Lijun XIAO ; Yirong GAN ; Chunli LIU ; Chengji LI ; Wen YANG ; Jiaoan PANG ; Jinhao TENG ; Yuan YU
Journal of Clinical Hepatology 2023;39(2):376-382
Objective To investigate the expression levels of scf and c-kit under the regulation of Dahuang Lingxian prescription and the possible mechanism of its effect on gallbladder dynamics, and to provide a theoretical basis for Dahuang Lingxian prescription in preventing the development and recurrence of cholesterol gallstone. Methods A total of 45 specific pathogen-free healthy male guinea pigs were randomly divided into normal group, model group, and traditional Chinese medicine (TCM) group. The guinea pigs in the normal group were fed with normal diet, and those in the model group and the TCM group were fed with high-fat lithogenic diet. After 8 weeks of feeding, 5 guinea pigs were randomly selected from each group, and successful modeling was determined if gallstone was observed with the naked eye in more than 4 guinea pigs. After successful modeling, the guinea pigs in the TCM group were given Dahuang Lingxian prescription by gavage, and those in the model group were given an equal volume of normal saline by gavage. After 8 consecutive weeks of administration by gavage, gallbladder tissue samples were collected, and HE staining was used to observe the pathological changes of gallbladder tissue; Western blot was used to measure the expression level of tumor necrosis factor-α (TNF-α) in gallbladder tissue; immunohistochemistry was used to measure the protein expression levels of scf and c-kit in gallbladder smooth muscle tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference multiple comparison method was used for further comparison between two groups. Results HE staining showed marked inflammation of gallbladder tissue in the model group, and compared with the model group, the TCM group had a significantly lower degree of inflammation. Western blot showed that the model group had the highest expression level of TNF-α in gallbladder tissue, followed by the TCM group and the normal group ( P < 0.05); immunohistochemistry showed that compared with the model group, the normal group and the TCM group had significantly higher protein expression levels of scf and c-kit in gallbladder smooth muscle tissue ( P < 0.05). Conclusion Dahuang Lingxian prescription can enhance the dynamic function of the gallbladder, possibly by upregulating the scf/c-kit signaling pathway in interstitial cells of Cajal in gallbladder.
9.Improvement Effects of Fibrinolytic Enzyme from Sipunculus nudus on Hemorheology Disorder and Vascular Endothelium Injury of Naked Acute Blood Stasis Model Rats
Yuanheng HUANG ; Xiaoliang HUANG ; Feizhang QIN ; Fusen LI ; Lijun PANG ; Yingxin LI
China Pharmacy 2019;30(19):2628-2631
OBJECTIVE: To study the improvement effects of fibrinolytic enzyme from Sipunculus nudus (SNFE) on hemorheology disorder and vascular endothelium injury in naked acute blood stasis model rats. METHODS: SD rats were randomly divided into control group, model group, aspirin group (100 mg/kg) and SNFE high-dose and low-dose groups (2 500, 5 000 U/kg), with 10 rats in each group. They were given relevant medicine intragastrically once a day, for consecutive 7 d. One hour after the 6th day of administration, except for control group, other groups were given adrenaline hydrochloride 0.8 mg/kg subcutaneously, and then the acute blood stasis model was induced by ice-water bath. Blood was collected from abdominal aorta 2 h after the next day. Blood rheological parameters such as whole blood viscosity (high, medium and low shear rate), plasma viscosity, hematocrit, erythrocyte aggregation index and erythrocyte deformability index were measured by automatic rheometer. The contents of NO and ET-1 in plasma and their ratio were determined by ELISA, and the damaged degree of vascular endothelium were observed by HE staining. RESULTS: Compared with control group, whole blood viscosity of high, medium and low-shear rate, plasma viscosity, erythrocyte aggregation index and ET-1 content were increased significantly in model group, while erythrocyte deformability index, NO content and NO/ET-1 ratio were decreased significantly, with statistical significance (P<0.05 or P<0.01). Compared with model group, whole blood viscosity of high, medium and low-shear rate, plasma viscosity, hematocrit, erythrocyte aggregation index and ET-1 content were decreased significantly in SNFE high-dose groups. Erythrocyte deformability index, NO content and NO/ET-1 ratio were increased significantly, with statistical significance (P<0.05 or P<0.01). In SNFE low-dose group, erythrocyte deformability index and NO/ET-1 ratio were increased significantly, while ET-1 content was decreased significantly, with statistical significance (P<0.05 or P<0.01). Vascular endothelial staining showed that compared with control group, the structure of aorta layers in model group was loose and disordered, the endothelial defect was incomplete, the vacuoles increased, and the endothelial damage was obvious. The endothelium of rats in each administration group was damaged to varying degrees, but the degree of injury was lighter than in model group. CONCLUSIONS: SNFE can improve hemorheological abnormalities and vascular endothelial injury in rats with acute blood stasis.
10.Tumor-suppressing effects of autophagy on hepatocellular carcinoma
Liver Research 2018;2(3):157-160
Evasion of apoptosis is one of the hallmarks of hepatocellular carcinoma(HCC)that results in treatment resistance.Recently,autophagy was reported to induce cell death in HCC,highlighting the tumor-suppressing effects of autophagy on HCC.This review summarizes our current understanding of the HCC-suppressing effects of macroautophagy(hereafter referred to as autophagy)to provide insights into the molecular mechanisms that may be essential for the development of autophagy-targeting thera-peutic strategies for HCC.

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