1.Pharmacodynamic Substances and Mechanisms of Xinglou Chengqi Tang in Treating Post-stroke Complications: A Review
Yujin ZHANG ; Xiangzhuo LIU ; Zhouyang CHEN ; Zihao SONG ; Xinyi LIU ; Yizhi YAN ; Chaoya LI ; Yingyan FANG ; Shasha YANG ; Xueqin CHENG ; Zhou XIE ; Sijie TAN ; Peng ZENG ; Yue ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):327-337
Stroke is the leading cause of death and disability among adults in China, and its common complications include digestive system abnormalities, cognitive impairment, depression, stroke-associated pneumonia, and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang (XLCQT) is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically, XLCQT is often used to treat stroke and its complications. However, the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally, since the basic research is weak, the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis, medicinal properties, safety evaluation, and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients, resveratrol, kaempferol, luteolin, chrysoeriol, apigenin, (+)-catechin, and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex, including inflammatory response, brain-gut axis, hypothalamic-pituitary-adrenal (HPA) axis, intestinal flora, neurotrophic factors, autophagy, oxidative stress, and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.
2.Qinlian Hongqutang Improves NASH by Promoting Macrophage Polarization Through TLR4 and STAT6 Signaling Pathways
Yong ZHANG ; Yong HU ; Yunliang HE ; Yang YANG ; Donghui CHEN ; Sijie DANG ; Jia HE ; Yaqi LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):10-20
ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang (QLHQT) on nonalcoholic steatohepatitis (NASH). MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling, mice were randomly assigned to the model group, low-, medium-, and high-dose QLHQT groups (0.51, 1.02, and 2.04 g·kg-1), and a positive control metformin group, with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), as well as hepatic TC, TG, and LDL-C contents, were determined by biochemical assays. Hematoxylin-eosin (HE) staining and oil red O staining were used to evaluate liver histopathology and lipid deposition, respectively. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Real-time polymerase chain reaction (Real-time PCR) were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group, body weight and serum and hepatic levels of TC, TG, and LDL-C were significantly increased in the model group (P<0.01). Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm, accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased, whereas the proportion of CD206-positive cells was markedly decreased (P<0.05). Hepatic inducible nitric oxide synthase (iNOS) levels and tumor necrosis factor-α (TNF-α) mRNA expression were significantly increased, while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased (P<0.01). The protein expression levels of Toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) in the liver were significantly increased (P<0.01). Compared with the model group, body weight was reduced in the high-, medium-, and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC, TG, and LDL-C levels were significantly decreased (P<0.01). Liver histopathology showed alleviated hepatic lipid deposition, with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased, whereas the proportions of CD206-positive cells were significantly increased in the high-, medium-, and low-dose QLHQT groups (P<0.05). Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased (P<0.01), whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased (P<0.01). The hepatic protein expression levels of TLR4, TRAF6, and MyD88 were significantly decreased, while signal transducer and activator of transcription 6 (STAT6) phosphorylation was significantly increased (P<0.05, P<0.01). There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice, and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.
3.Qinlian Hongqutang Improves NASH by Promoting Macrophage Polarization Through TLR4 and STAT6 Signaling Pathways
Yong ZHANG ; Yong HU ; Yunliang HE ; Yang YANG ; Donghui CHEN ; Sijie DANG ; Jia HE ; Yaqi LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):10-20
ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang (QLHQT) on nonalcoholic steatohepatitis (NASH). MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling, mice were randomly assigned to the model group, low-, medium-, and high-dose QLHQT groups (0.51, 1.02, and 2.04 g·kg-1), and a positive control metformin group, with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), as well as hepatic TC, TG, and LDL-C contents, were determined by biochemical assays. Hematoxylin-eosin (HE) staining and oil red O staining were used to evaluate liver histopathology and lipid deposition, respectively. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Real-time polymerase chain reaction (Real-time PCR) were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group, body weight and serum and hepatic levels of TC, TG, and LDL-C were significantly increased in the model group (P<0.01). Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm, accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased, whereas the proportion of CD206-positive cells was markedly decreased (P<0.05). Hepatic inducible nitric oxide synthase (iNOS) levels and tumor necrosis factor-α (TNF-α) mRNA expression were significantly increased, while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased (P<0.01). The protein expression levels of Toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) in the liver were significantly increased (P<0.01). Compared with the model group, body weight was reduced in the high-, medium-, and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC, TG, and LDL-C levels were significantly decreased (P<0.01). Liver histopathology showed alleviated hepatic lipid deposition, with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased, whereas the proportions of CD206-positive cells were significantly increased in the high-, medium-, and low-dose QLHQT groups (P<0.05). Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased (P<0.01), whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased (P<0.01). The hepatic protein expression levels of TLR4, TRAF6, and MyD88 were significantly decreased, while signal transducer and activator of transcription 6 (STAT6) phosphorylation was significantly increased (P<0.05, P<0.01). There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice, and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.
4.Role of sphingolipid metabolism signaling in a novel mouse model of renal osteodystrophy based on transcriptomic approach.
Yujia WANG ; Yan DI ; Yongqi LI ; Jing LU ; Bofan JI ; Yuxia ZHANG ; Zhiqing CHEN ; Sijie CHEN ; Bicheng LIU ; Rining TANG
Chinese Medical Journal 2025;138(1):68-78
BACKGROUND:
Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq).
METHODS:
Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS:
By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR.
CONCLUSIONS
Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals
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Mice
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Chronic Kidney Disease-Mineral and Bone Disorder/genetics*
;
Male
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Disease Models, Animal
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Mice, Inbred C57BL
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Sphingolipids/metabolism*
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Transcriptome/genetics*
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Signal Transduction/genetics*
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X-Ray Microtomography
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Adenine
5.Comparative study on accuracy of three imaging methods in diagnosis of subacromial impingement syndrome.
Linfeng ZI ; Hongfu JIN ; Jianwei ZHU ; Guoxu ZHANG ; Yao TONG ; Sijie CHEN ; Wenze SHAO ; Xin TANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(10):1290-1295
OBJECTIVE:
To compare the diagnostic accuracy of supraspinatus muscle outlet X-ray film, oblique sagittal multislice helical CT (MSCT), and oblique sagittal MRI in the diagnosis of subacromial impingement syndrome (SIS).
METHODS:
A retrospective analysis was conducted on the imaging data of 106 patients diagnosed with SIS between January 2023 and December 2024. The cohort consisted of 32 males and 74 females, with ages ranging from 43 to 70 years (mean, 60.19 years). All patients underwent supraspinatus muscle outlet X-ray film, MSCT, and MRI scans, with MSCT further subjected to three-dimensional reconstruction. Two experienced radiologists independently evaluated the acromion morphology in each imaging modality using the Bigliani classification system. Inter-observer reliability was assessed via Kappa statistics. The CT three-dimensional reconstructions were used as the "gold standard". The overall consistency, Kappa values, sensitivity, and specificity of the three imaging modalities were calculated. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was computed.
RESULTS:
The inter-observer reliability for supraspinatus muscle outlet X-ray film, oblique sagittal MSCT, and oblique sagittal MRI was moderate, with Kappa values of 0.62, 0.63, and 0.55, respectively. When compared to the CT three-dimensional reconstructions as the "gold standard", the overall consistency was 88.7% (94/106), 62.3% (66/106), and 58.5% (62/106), respectively. The supraspinatus muscle outlet X-ray film showed excellent consistency (Kappa=0.77), whereas the consistency of MSCT and MRI was lower (Kappa=0.34 and 0.29, respectively). In terms of diagnostic sensitivity and specificity, the supraspinatus muscle outlet X-ray film outperformed oblique sagittal MSCT and oblique sagittal MRI in distinguishing various acromion types. ROC analysis demonstrated that the AUC for the supraspinatus muscle outlet X-ray film was consistently higher than for oblique sagittal MSCT and oblique sagittal MRI, with the highest diagnostic performance observed for type Ⅲ hooked acromion (AUC=0.939).
CONCLUSION
Supraspinatus muscle outlet X-ray film provides the highest diagnostic accuracy for acromion classification in SIS patients, particularly in identifying type Ⅲ hooked acromion, which is strongly associated with SIS. Given its superior sensitivity and consistency, it should be considered the primary screening tool. MSCT and MRI serve as valuable supplementary modalities for complex cases and preoperative evaluation.
Humans
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Middle Aged
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Male
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Female
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Shoulder Impingement Syndrome/diagnostic imaging*
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Magnetic Resonance Imaging/methods*
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Retrospective Studies
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Aged
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Adult
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Imaging, Three-Dimensional
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Sensitivity and Specificity
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Tomography, Spiral Computed/methods*
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Multidetector Computed Tomography/methods*
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Reproducibility of Results
6.Evaluation and analysis for effect of managing equipment on the basis of information-based management for medical images
Fan ZHANG ; Xinchi LIU ; Yabin ZHANG ; Sijie XIU
China Medical Equipment 2025;22(7):157-161
Objective:To analyze the management benefits of information-based management mode for medical imaging equipment,and promote rational management for equipment and improve management benefits of equipment.Methods:According to the existing information management system and electronic medical record system at Tangdu hospital,Air Force Medical University,a management platform for medical imaging equipment under information-based management mode for medical imaging equipment was constructed to manage medical imaging equipment.A total of 9 imaging equipment included magnetic resonance(MR)equipment,computed tomography(CT)equipment and X-ray equipment that were in clinical use during 2022 and 2023 were selected,and the conventional management mode was adopted to manage equipment during January and December 2022,and the information-based management mode was adopted to manage them during January and December 2023.The comprehensive management benefits of the two modes for medical imaging equipment were compared.A self-designed questionnaire was used to survey satisfaction levels of 80 patients who underwent diagnosis and treatment by using these equipment.Results:The annual examination amount,annual revenue,annual operating cost,and annual net profit of MRI,CT,and X-ray equipment of adopting information-based management mode were all higher than those of adopting conventional management mode,and the investment payback period was shorter than that of adopting conventional management mode,and the cost-effectiveness evaluation was superior to conventional management mode.The average utilization rate of equipment,rate of maintenance and upkeep,and rate of controlling risk of adopting information-based management mode were respectively(95.36±6.02)%,(92.36±4.36)%and(94.36±4.15)%,which were significantly higher than those of adopting conventional management mode(t=14.317,11.62,12.508,P<0.05).Patients'satisfactions for MRI equipment,CT equipment and X-ray equipment that adopted information-based management mode were significantly higher than these that adopted conventional management mode,and the differences were significant(x2=5.741,6.260,5.331,P<0.05).Conclusion:The information-based management mode for medical imaging equipment can real-timely obtain the situations of usage and monitoring for medical imaging equipment,and enhance cost-effectiveness and management effectiveness at the maximum extent,and enhance users'satisfaction in using medical equipment.
7.Curcumin ameliorates the pathogenesis of IgA nephropathy by regulating intestinal mucosal immunity through inhibition of Toll-like receptor 9/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway
Ziyang YE ; Qi DUAN ; Feng WU ; Xiaotong LI ; Sijie ZHANG ; Yafeng LI
Chinese Journal of Nephrology 2025;41(5):358-371
Objective:To explore the role of curcumin (Cur) in improving IgA nephropathy (IgAN) and its related mechanisms.Methods:Fifty 7-month-old miR-23b knockout (miR-23b -/-) mice weighing (25±5) g were used to establish an IgAN disease model, and were randomly divided into IgAN group, IgAN+Cur (150 mg/kg) group and IgAN+Cur (300 mg/kg) group using simple randomisation. Sixteen healthy 7-month-old weighing (25±3) g C57BL/6J wild-type mice served as the normal control group. IgAN+Cur (150 mg/kg) and IgAN+Cur (300 mg/kg) groups were respectively gavaged continuously with 150 mg/kg Cur and 300 mg/kg Cur for 8 weeks, and the normal control and IgAN groups were gavaged continuously with an equal dose of 0.9% sodium chloride solution for 8 weeks. The samples of urine, serum, intestinal fluid, intestinal tissues, kidney tissues and liver tissues were collected from each group. In vitro experiments, human cloned colon adenocarcinoma (Caco-2) cells were divided into blank control (Ctrl), Ctrl+Cur (10 μmol/L), Ctrl+ Cur (60 μmol/L), tumor necrosis factor-α(TNF-α), TNF-α+Cur (10 μmol/L) and TNF-α+Cur (60 μmol/L) groups. Enzyme-linked immunosorbent assay was used to detect serum alanine transaminase, aspartate transaminase, secretory IgA (sIgA), creatinine, blood urea nitrogen, 24 h urine microalbumin, as well as sIgA, TNF-α, interleukin(IL)-6 and IL-1β in the intestinal fluids. HE staining was used to observe the effect of Cur on liver tissues, the hyperplasia of glomerular mesangial zone in kidney tissues and the morphological and structural changes of intestinal epithelial barrier, and the histopathological damage scores were performed respectively. PAS staining was used to observe the changes of glomerular basement membrane and mesangial matrix. Immunofluorescence was used to observe the deposition of immune complexes in the glomerular mesangial zone. Real-time quantitative PCR was used to detect the mRNA expression levels of B-cell activating factor ( BAFF) and a proliferation inducing ligand ( APRIL). Western blotting was used to detect the protein expression levels of tight junction proteins zonula occluden-1 (ZO-1) and occludin in the mouse intestinal tissues. The potential targets of Cur in IgAN were predicted. Western blotting was used to detect the protein expression levels of tight junction proteins, as well as Toll-like receptor 9 (TLR9), myeloid differentiation primary response protein (MyD88), nuclear factor-κB p65 (NF-κB p65) and p-NF-κB p65. Results:Genetic identification results revealed that all IgAN model mice exhibited the miR-23b -/- genotype, confirming successful model establishment. Seven-month-old mice were subsequently selected for Cur treatment. Histopathological analysis demonstrated no significant differences in hepatic tissue morphology across groups, with comparable liver histopathological injury scores and unaltered liver function parameters, thereby validating the safety of Cur administration. Compared with the normal control group, IgAN mice displayed elevated levels of serum sIgA, serum creatinine, blood urea nitrogen and 24 h urine microalbumin (all P<0.05). Renal pathological results revealed severe mesangial hypercellularity in glomeruli, higher glomerular injury scores, and notable glomerular mesangial deposits of IgA, IgG and complement C3 in IgAN mice (all P<0.05). Additionally, intestinal pathological alterations were observed, including structural changes in intestinal epithelium and Peyer's patches, accompanied by significantly higher intestinal histopathological injury scores in IgAN mice ( P<0.05). Intestinal epithelial expression levels of ZO-1 and occludin were significantly reduced, while sIgA, TNF-α, IL-1β and IL-6 in intestinal fluid were elevated (all P<0.05). Serum FITC fluorescence intensity was markedly increased, and intestinal tissue exhibited upregulated mRNA expression of BAFF and APRIL (all P<0.05). Following Cur treatment, serum sIgA level and renal function indices in mice showed partial recovery (all P<0.05). Renal pathological improvements included alleviated mesangial hypercellularity, reduced glomerular injury scores, and diminished glomerular immune complex deposition (all P<0.05). Intestinal pathologies, including epithelial and Peyer's patch lesions, were mitigated, with decreased intestinal histopathological injury scores ( P<0.05). Additionally, intestinal tight junction protein expression levels were upregulated, intestinal fluid sIgA level was reduced, inflammatory markers were attenuated, serum FITC fluorescence intensity was declined, and intestinal BAFF and APRIL mRNA expression levels were downregulated (all P<0.05). In vitro experiments demonstrated that TNF-α exposure reduced tight junction protein expression in Caco-2 cells, whereas Cur treatment reversed the effect (all P<0.05). Target prediction analysis revealed that Cur effectively bound to TLR9 structural domain in IgAN. Experimental validation confirmed that Cur treatment suppressed the upregulated protein expression levels of TLR9, MyD88, NF-κB p65 and p-NF-κB p65 in intestinal tissues of IgAN mice (all P<0.05). Conclusion:Cur has a significant effect in the treatment of IgAN and can regulate intestinal mucosal immunity by inhibiting the TLR9/MyD88/NF-κB signaling pathway, thereby reducing renal injury and protecting the kidneys.
8.Research on the alleviation of podocyte injury in lupus nephritis by proscillaridin A and its mechanism
Ruxu LI ; Sijie ZHOU ; Mingyang HU ; Chunyi ZHANG ; Congcong GAO ; Chaoying LI ; Kebing SHEN ; Zhangsuo LIU ; Zhaohui ZHENG
Chinese Journal of Nephrology 2025;41(9):677-686
Objective:To investigate the protective effect and its mechanism of proscillaridin A (PSD-A) on podocyte injury in lupus nephritis (LN).Methods:Molecular docking and surface plasmon resonance techniques were used to analyze the binding status of PSD-A to signal transducer and activator of transcription 1 (STAT1). The immortalized human podocyte injury model in the lupus group was induced by the serum of systemic lupus erythematosus patients, and the control and PSD-A intervention (2 nmol/L, 4 nmol/L) groups were also set up. Six female 12-week-old C57BL/6 mice were designated as the control group, and 12 female 12-week-old MRL/lpr lupus mice were randomly divided into lupus group and PSD-A intervention group by random number table method. The PSD-A intervention group was intraperitoneally injected with 5 mg/kg PSD-A, once per week for 6 consecutive weeks. While the control group and the lupus group were intraperitoneally injected with the same volume of the solvent without PSD-A. Western blotting and real-time quantitative PCR were employed to detect the relative protein and mRNA expression levels of podocin, STAT1, and interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) in podocytes of each group. Enzyme-linked immunosorbent assay was used to detect the levels of serum anti-double strand DNA antibody and interferon-α in mice. Coomassie brilliant blue was used to detect the urinary protein level. HE, PAS, Masson and PASM staining and transmission electron microscopy were used to observe the pathological changes of renal tissues. Immunohistochemistry was used to examine the protein expression of podocin, STAT1 and IFIT1 in renal tissues.Results:Molecular docking and surface plasmon resonance techniques proved that PSD-A could bind to STAT1 protein and they exhibited a robust binding affinity. The podocyte experiments showed that, compared with the lupus group, the relative expression levels of podocin protein and mRNA in the PSD-A intervention group were upregulated, while the relative expression levels of STAT1 and IFIT1 protein and mRNA were downregulated (all P<0.05). The animal experiments showed that, compared with the lupus group, the serum levels of anti-double strand DNA antibody, interferon-α, and urinary protein in PSD-A intervention group were decreased, the pathological damage of renal tissues was alleviated, and the injury of renal podocytes was reduced. Immunohistochemical staining showed that the relative protein expression levels of STAT1 and IFIT1 of renal tissues in the PSD-A intervention group were lower than those in the lupus group (all P<0.05). Conclusion:PSD-A can play a protective role in podocyte injury in LN, and its mechanism may be related to the inhibition of the STAT1 signaling pathway.
9.Analysis of prognostic factors for esophageal cancer after radical resection and the applica-tion value of machine learning prediction model
Yue ZHAO ; Sijie ZHANG ; Haiming LI ; Yijun MA ; Zhan ZHANG ; Zhenyi LI ; Junjie LIU ; Hui TIAN ; Yu TIAN
Chinese Journal of Digestive Surgery 2025;24(10):1305-1317
Objective:To investigate the prognostic factors for esophageal cancer after radical resection and the application value of machine learning prediction model.Methods:The retrospective cohort study was conducted. The clinicopatholigical data of 406 esophageal cancer patients who were admitted to Qilu Hospital of Shandong University from January 2018 to March 2022 were collected. There were 357 males and 49 females, aged (64±8)years. All patients underwent radical resection of esophageal cancer. The 406 patients were randomly divided into a training set of 285 cases and a validation set of 121 cases at a 7∶3 ratio based on a random number table. The training set was used to construct prediction model, and the validation set was used to validate prediction model. Patients were divided into high-risk group and low-risk group based on risk scores. Observation indicators: (1) follow-up of patients and analysis of influencing factors for prognosis; (2) construction and validation of machine learning prediction models. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and the Log-rank test was used for survival analysis. The Cox proportional hazard regression model was used for univariate and multivariate analyses. Independent influencing factors were included, and data processing, machine learning model construction, and visualization were performed using R packages including random survival forest (RSF), gradient boosting machine (GBM), least absolute shrinkage and selection operator Cox regression (LASSO-Cox), Cox proportional hazards model boosting (CoxBoost), survival support vector machine (survivalsvm), extreme gradient boosting (XGBoost), supervised principal component analysis (SuperPC), and Cox partial least squares regression (plsRcox). Receiver operating characteristic (ROC) curves were drawn, and sensitivity, specificity, and area under the curve (AUC) were calculated. The Delong test was used to assess the differences in AUC among different models in the training set, and the time-dependent ROC was used to compare the predictive performance of different models. Calibration curves were used to evaluate model accuracy, and decision curve analysis (DCA) was used to evaluate overall net benefit. Results:(1) Follow-up of patients and analysis of influencing factors for prognosis. All 406 patients were followed up postoperatively for 28(range, 6-36)months, with 1- and 3-year overall survival rate of 86.5% and 40.9%, respectively. The 285 patients in the training set were followed up postoperatively for 30(range, 6-36)months, with 1- and 3-year overall survival rate of 85.1% and 35.5%, respectively. The 121 patients in the validation set were followed up postoperatively for 25(range, 6-36)months, with 1- and 3-year overall survival rate of 87.0% and 43.2%, respectively. There was no significant difference in postoperative overall survival rate between the training set and the validation set ( χ2=3.20, P>0.05). Results of multivariate analysis showed that left thoracic surgical approach, preopera-tive neutrophil count, vascular invasion, perineural invasion, pathological T2-4 stage, pathological N2-3 stage, and postoperative pneumonia were independent risk factors affecting postoperative survival of 285 patients in the training set ( hazard ratio=1.466, 1.037, 1.482, 1.549, 5.268, 7.727, 22.202, 2.539, 2.686, 1.425, 95% confidence interval as 1.026-2.096, 1.003-1.073, 1.008-2.179, 1.105-2.170, 1.201-23.099, 1.833-32.576, 4.734-104.128, 1.577-4.087, 1.631-4.422, 1.018-1.994, P<0.05). (2) Construction and validation of machine learning prediction models. Independent risk factors affecting postoperative survival were included to construct RSF, GBM, LASSO-Cox, CoxBoost, survivalsvm, XGBoost, SuperPC, and plsRcox machine learning prediction models. Results of Delong test showed that there were significant differences in the AUC of RSF and GBM from the other six models ( P<0.05). Results of time-dependent ROC curve showed that all 8 machine learning predic-tion models had good discriminative ability in the training cohort, among which the RSF machine learning prediction model had the best predictive performance. Results of calibration curve showed that the RSF machine learning prediction model fitted well for predicting postoperative 1-, 2-, and 3-year overall survival in the training cohort, with high consistency with actual results. Results of decision curve analysis showed that within a threshold range of 0-0.80, the RSF machine learning prediction model provided a better overall net benefit. Further analysis showed that in the validation set, the AUC of RSF machine learning prediction model for postoperative 1-, 2-, and 3-year survival prediction were 0.786 (95% confidence interval as 0.609-0.962), 0.774 (95% confidence interval as 0.676-0.873), and 0.750 (95% confidence interval as 0.652-0.848), respectively. Results of calibration curve showed that the RSF machine learning prediction model fitted well for predicting postopera-tive 1-, 2-, and 3-year overall survival in the validation set, with high consistency with actual results. In the training set, the optimal cutoff value of the RSF machine learning prediction model risk score was 11.7. Patients with risk score ≥11.7 were classified as the high-risk group, and those with risk score <11.7 as the low-risk group. The median survival times of the two groups were 18.0 months and >36.0 months, respectively, showing a significant difference between them ( χ2=73.30, P<0.05). In the validation set, the optimal cutoff value of the RSF machine learning prediction model risk score was 11.7. Patients with risk score ≥11.7 were classified as the high-risk group, and those with risk score<11.7 as the low-risk group. The median survival times of the two groups were 17.0 months and>36.0 months for the high-risk and low-risk groups, respectively, showing a significant difference between them ( χ2=35.20, P<0.05). Conclusions:Left thoracic surgical approach, preoperative neutrophil count, vascular invasion, perineural invasion, pathological T2-4 stage, pathological N2-3 stage, and postoperative pneumonia are independent risk factors affecting survival of esophageal cancer patients after radical resection. The RSF machine learning prediction model constructed based on these factors can effectively distinguish the survival prognosis of high-risk and low-risk patients.
10.Analysis of the diagnostic and therapeutic value of single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis therapy for the acute uncomplicated appendicitis
Sijie GUO ; Hongguang WANG ; Liying TAO ; Qingmei GUO ; Xiang GUO ; Lianyu PIAO ; Jiwei ZHANG ; Lin LIU
China Journal of Endoscopy 2025;31(11):55-61
Objective To investigate the diagnostic and therapeutic value of single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis therapy in the treatment of acute uncomplicated appendicitis.Methods A retrospective analysis was conducted on the clinical data of 39 patients with acute uncomplicated appendicitis who underwent single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis treatment at the Endoscopy center of the hospital from September 2022 to September 2024.Observe the endoscopic manifestations,the rate of maternal and child basket stone removal,the rate of appendiceal stent implantation,the technical success rate,the clinical success rate,the operation time,the hospital stay,the incidence of complications,the visual analogue scale(VAS)score 6 hours after the operation,and the inflammatory indicators 24 hours after the operation.Results In 28 cases(71.8%),congestion and edema could be seen at the opening of the appendix under colonoscopy.In 10 cases(25.6%),pus could be seen flowing out of the opening of the appendix under colonoscopy.In 32 cases(82.1%),a large amount of pus could be seen in the lumen of the appendix under subscopy.In 20 cases(51.3%),appendiceal fecalith could be seen in the lumen of the appendix under subscopy.The technical success rate of single-use mother-baby choledochoscope-assisted endoscopic retrograde appendicitis treatment was 100.0%(39/39).The operation time was(21.08±7.49)min;Hospital stay:(3.97±2.08)days;Eight cases(20.5%)of patients underwent endoscopic maternal basket stone removal.Appendiceal stent implantation was performed in 14 cases(35.9%)of patients.The clinical success rate is 97.4%(38/39).One patient's clinical symptoms and inflammatory indicators did not improve after the operation,and was transferred to the surgery department for appendectomy.The VAS score of 38 patients was less than 3 points 6 hours after the operation,and the abdominal pain symptoms were significantly relieved.The white blood cell count and the percentage of neutrophils 24 hours after the operation decreased significantly compared with those before the operation,and the differences were statistically significant(P<0.05).None of the 39 patients had complications.The postoperative follow-up was(5.94±4.03)months,and recurrence occurred in 3 cases(7.7%).Conclusion single-use mother-baby choledocoscope-assisted endoscopic retrograde appendicitis therapy is safe and effective in the diagnosis and treatment of acute uncomplicated appendicitis,which is worthy of further promotion and popularization in clinical practice.

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