1.Effect of Modified Tuoli Xiaodusan on Patients After Perianal Abscess Surgery on STAT3/VEGF Pathway
Haoyang DU ; Yuan GAO ; Haiqi FU ; Jinling HE ; Jing ZHANG ; Yangyang YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):187-195
ObjectiveTo explore the clinical efficacy of oral administration of modified Tuoli Xiaodusan on postoperative patients with perianal abscess, and its effects on related inflammatory factors and signal transducers and activators of transcription protein 3 (STAT3)/vascular endothelial growth factor (VEGF) signaling pathways. MethodsFrom January 2023 to December 2023 in Inner Mongolia hospital of traditional Chinese medicine, 60 postoperative patients with perianal abscess who met the inclusion criteria were selected. They were divided into a treatment group and a control group using the random number table method, with 30 cases in each group. The control group received conventional treatment, while the treatment group received additional treatment with modified Tuoli Xiaodusan on the basis of the control group. The course of treatment in both groups was three weeks. On the day of operation and on the 7th, 14th and 21st day after operation, enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of serum interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Hematoxylin eosin (HE) staining was used to observe the pathological morphology of pathological tissue. Western blot was used to measure the levels of phosphorylated STAT3 (p-STAT3) and vascular endothelial growth factor (VEGF) proteins, and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to determine the expression level of VEGF mRNA. The clinical efficacy of the two groups was compared according to the wound pain, secretion volume score, and healing rate of patients on the 3rd, 7th, 14th, and 21st day after operation. ResultsThe total effective rate of the treatment group was higher than that of the control group (P<0.05). For intra-group comparison, the pain score of the control group decreased at each time period (P<0.05), and the healing rate increased (P<0.05). The secretion volume score decreased on the 14th and 21st days after operation (P<0.05). The pain score and secretion volume score of the treatment group decreased at each time period (P<0.05), and the healing rate increased (P<0.05). The levels of various inflammatory factors decreased in both groups (P<0.05). Compared with those on the surgical day, the levels of p-STAT3 and VEGF proteins in the wound tissue of the two groups were different on the 7th and 21st days after operation (P<0.05). There were significant differences in VEGF mRNA levels in wound tissue between the two groups at each time period (P<0.01). For inter-group comparison, on the 7th and 14th days after operation, the pain score in the treatment group was lower than that in the control group. On the 7th, 14th and 21st days after operation, the secretion volume scores and healing rate of the treatment group were better than those of the control group (P<0.05). The levels of various inflammatory factors in the treatment group were lower than those in the control group (P<0.05), and the decline rate was faster (P<0.05). On the 7th day after operation, the levels of p-STAT3, VEGF protein, and VEGF mRNA in the wound tissue of the treatment group were higher than those in the control group (P<0.05). HE staining showed that the inflammatory cell infiltration in the treatment group decreased faster. The cell arrangement was more orderly, and new blood vessel lumens were visible. There were no abnormalities in the safety observation indexes of all patients during the study period. ConclusionModified Tuoli Xiaodusan can relieve wound pain after perianal abscess surgery, reduce secretions, and improve wound healing rate. The mechanism may be reducing the levels of serum IL-1β, IL-6, and TNF-α, reducing the inflammatory response of the wound, upregulating the expression of p-STAT3 and VEGF proteins, and stimulating the STAT3/VEGF signaling pathway, thereby accelerating angiogenesis and promoting wound healing.
2.Comparison of Wild and Cultivated Bupleurum scorzonerifolium Based on Traditional Quality Evaluation
Changsheng YUAN ; Feng ZHOU ; Xingyu LIU ; Yu SHI ; Yihan WANG ; Huaizhu LI ; Yongliang LI ; Shan GUAN ; Huaizhong GAO ; Yanmeng LIU ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):203-214
ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots(BSR), and explore the underlying molecular mechanisms, providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin(YLW) served as the quality reference, we conducted comparative analysis among YLW, locally domesticated wild germplasm in Yulin(YLC3), Daqing germplasm introduced and cultivated in Yulin(YLDQC3), and locally cultivated germplasm in Daqing(DQC3). A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed, including macroscopic traits(appearance, odor), microscopic features(proportions of cork, phloem, xylem), cell wall component contents(hemicellulose, cellulose, lignin), carbohydrate contents(starch, water-soluble polysaccharides), marker compound contents(ethanol-soluble extracts, total saponins, liposoluble extracts, and saikosaponins A, B2, C, D), metabolomics, and transcriptomics, in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically, Yulin-produced BSR(YLW, YLC3, YLDQC3) exhibited significantly greater weight, length, and upper and middle diameters than Daqing-produced BSR(DQC3). Odor-wise, YLW and YLC3 had a a fragrance taste, YLDQC3 had a rancid oil odor, and DQC3 had a sweet and fragrant taste. Microscopically, Yulin germplasm(YLW, YLC3) and Daqing germplasm(YLDQC3, DQC3) shared similar structural features, respectively. However, Yulin germplasm showed significantly higher proportions of cork and phloem, as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents, Yulin germplasm contained significantly higher levels of ethanol-soluble extracts, total saponins, and saikosaponins A, B2, C, D, while Daqing germplasm had significantly higher levels of hemicellulose, starch, and liposoluble extracts. After introduction to Yulin, the Daqing germplasm(YLDQC3) showed increased starch, water-soluble polysaccharides and liposoluble extracts contents, decreased cell wall component content, but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm, while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway, including one acetyl-coenzyme A(CoA) acetyltransferase gene(ACAT), one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene(HMGS), two hydroxymethylglutaryl-CoA(HMG-CoA) reductase genes(HMG), one phosphomevalonate kinase gene(PMK), one 1-deoxy-D-xylose-5-phosphate synthase gene(CLA), one hydroxymethylbuten-1-aldol synthase gene(HDR), two farnesyl pyrophosphate synthase genes(FPPS), one squalene synthase gene(SQS), one β-amyrin synthase gene(BAS), 102 cytochrome P450(CYP450) gene family members, and 32 uridine diphosphate-glucuronosyltransferase(UGT) gene family members. ConclusionAmong the three cultivated types, YLC3 most closely resembles YLW in appearance, microscopic features, contents of major bioactive constituents, metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm, and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings, it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.
3.Value of immunoglobulin G/immunoglobulin M ratio in predicting the prognosis of patients with initially unresectable hepatocellular carcinoma treated by transcatheter arterial chemoembolization combined with tyrosine kinase inhibitor and programmed cell death protein-1 inhibitor
Xingzhi LI ; Wei LUO ; Yuan FENG ; Yu CAI ; Xiaohong LIU ; Feixiang WU ; Yong PENG
Journal of Clinical Hepatology 2026;42(1):117-124
ObjectiveTo investigate the association between immunoglobulin G (IgG)/immunoglobulin M (IgM) ratio and prognosis in patients with initially unresectable hepatocellular carcinoma (iuHCC) receiving TTP triple therapy with transcatheter arterial chemoembolization (TACE), tyrosine kinase inhibitor (TKI), and programmed cell death protein-1 (PD-1) inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, from November 2019 to December 2022, and according to IgG/IgM ratio, they were divided into high IgG/IgM group (IgG/IgM ratio >13.23) and low IgG/IgM group (IgG/IgM ratio ≤13.23). The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis, and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival (OS). ResultsThe 151 patients had a median OS of 26.7 months (95% confidence interval [CI]: 19.8-not reached) and a median progression-free survival of 12.5 months (95%CI: 10.4 — 15.8). The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group (all P>0.05). There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group (20.6 months vs not reached, P=0.016). In both the high IgG/IgM group and the low IgG/IgM group, salvage hepatectomy was significantly associated with the improvement in OS (χ2=8.297 and 10.307, both P<0.05). The multivariate analysis showed that high IgG/IgM ratio (hazard ratio [HR]=1.799, 95%CI: 1.077 — 3.006, P=0.025), baseline alpha-fetoprotein >400 ng/mL (HR=1.762, 95%CI: 1.017 — 3.050, P=0.043), and BCLC stage (HR=2.265, 95%CI: 1.212 — 4.232, P=0.010) were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy, and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.
4.Evaluation of the application of a predictive model for red blood cell demand in surgical procedures
Xiaoyu CAI ; Yannan FENG ; Chunya MA ; Yuan ZHUANG ; Yang YU
Chinese Journal of Blood Transfusion 2026;39(1):51-55
Objective: To assess the clinical application value of a prediction model for red blood cell (RBC) demand in surgical procedures. Methods: Demographic data, laboratory parameters, anesthesia and transfusion records, and model prediction data were retrospectively collected from surgical patients at the First Medical Center of Chinese PLA General Hospital between 2018 and 2024. Statistical analysis was performed using the Chi-square test, t-test, and Mann-Kendall trend test. Results: From 2018 to 2024, the predictive model for RBC demand in surgical procedures was used to evaluate a total of 112 293 surgeries. During this period, the model call rate (77.49%-98.91%, P<0.05), compliance rate (56.81%-84.92%, P<0.05), and prediction accuracy rate (66.82%-94.17%, P<0.05) all showed significant upward trends. The total blood usage across the hospital (13645.4-7723.5 units, P<0.05) and the average blood usage per surgery (0.21-0.1 units, P<0.05) exhibited overall downward trends. Postoperative average hemoglobin levels in the non-compliance group (112.1-105.3 g/L in the non-compliance group vs 106.9-92.7 g/L in the compliance group, P<0.05) and the intraoperative excessive transfusion rate (5.06%-6.05% in the non-compliance group vs 0.09%-0.04% in the compliance group, P<0.05) were significantly higher in the non-compliance group compared to the compliance group. Conclusion: The predictive model for RBC demand in surgical procedures has played a positive role in conserving blood resources, optimizing blood resource allocation, and reducing intraoperative risks.
5.Regulation of Rat Intervertebral Disc Annulus Fibrosus Cell Proliferation and Apoptosis by Yaoshu Zhuyu Fang via miR-17-5P/MDM2/p53 Pathway
Haitao JIANG ; Hantao YUAN ; Wenting HUANG ; Rongrong YANG ; Xiaochun CHEN ; Baoqing YU ; Sibo LI
Laboratory Animal and Comparative Medicine 2026;46(1):55-65
ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.
6.Advances in the JAK2/STAT3 signaling pathway and its inhibitors in diffuse large B cell lymphoma
Chuanyang LU ; Qiuni CHEN ; Yuye SHI ; Yuan DENG ; Tingting JI ; Zhengyuan LIU ; Chunling WANG ; Liang YU
China Pharmacy 2026;37(5):682-688
Abnormal activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma (DLBCL). In recent years, inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors (e.g., ruxolitinib) and STAT3 inhibitors (direct small-molecule inhibitors, the antisense oligonucleotide, and proteolysis targeting chimeras, etc.) in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile, the development of novel drug delivery systems has significantly enhanced the stability, bioavailability, and targeting ability of the compounds. Furthermore, JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies (such as combinations with B-cell receptor signaling pathway inhibitors, immunomodulators, or other targeted drugs). However, current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL, and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.
7.Chufeng Yisuntang Ameliorates PM2.5-induced Dry Eye via ROS/p38 MAPK Signaling Pathway
Yuan ZHONG ; Pan ZHAO ; Shi TAN ; Yu TANG ; Dongdong LI ; Lihao CHEN ; Jun PENG ; Qinghua PENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):191-200
ObjectiveTo establish a mouse model of particulate matter 2.5 (PM2.5)-induced dry eye and investigate whether Chufeng Yisuntang can ameliorate the PM2.5-induced ocular surface damage by regulating the reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MethodsSixty 8-week-old male C57BL/6J mice were used. Ten were randomly selected as the control group. The remaining 50 mice received topical instillation of 1 drop (0.1 mL) of 5 g·L-1 PM2.5 suspension in both eyes, four times daily. Successfully modeled mice were randomized into four groups (n=10): Model, p38 MAPK inhibitor, Chufeng Yisuntang, and combination (Chufeng Yisuntang at 7.3 g·kg-1 + p38 MAPK inhibitor SB203580 at 5 mg·kg-1). Chufeng Yisuntang was administered via gavage, and the inhibitor group via intraperitoneal injection. The control and model groups received equal volumes of distilled water by gavage. All treatments lasted for 4 weeks. General conditions were dynamically observed. Tear secretion, tear film break-up time, and corneal fluorescein staining were assessed. After intervention for 4 weeks, hematoxylin and eosin (HE) staining was used to examine the histopathological changes. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure serum levels of ROS, malondialdehyde (MDA), superoxide dismutase (SOD) 1, and SOD2. Western blot and Real-time PCR were employed to determine the protein and gene levels, respectively, of p38 MAPK, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cysteinyl aspartate-specific proteinase-3 (Caspase-3) in the corneal tissue. ResultsCompared with the control group, the model group exhibited reduced tear secretion volume and tear film breakup time, along with increased corneal fluorescein staining scores (P<0.01). Compared with the model group, the Chufeng Yisuntang group, p38 MAPK inhibitor group, and combination group demonstrated increased tear secretion volume and tear film breakup time, along with decreased corneal fluorescein staining scores (P<0.01). HE staining revealed that compared with the control group, the model group exhibited marked increases in corneal epithelial cell layers and epithelial thickness, along with reduced meibomian gland acini and intensely stained, densely packed nuclei around the acini. Compared with the model group, the Chufeng Yisuntang group, p38 MAPK inhibitor group, and combination group showed intact corneal structure, improved cell morphology, and reduced damage severity. ELISA revealed elevated ROS and MDA levels (P<0.01) and decreased SOD1 and SOD2 levels (P<0.01) in the model group compared with the control group. Compared with the model group, Chufeng Yisuntang, p38 MAPK inhibitor, and the combination lowered ROS and MDA levels (P<0.01), while raising SOD1 and SOD2 levels (P<0.05, P<0.01). Western blot revealed that compared with the control group, the model group exhibited increased protein levels of p38 MAPK, Bax, and Caspase-3 (P<0.01) and reduced protein level of Bcl-2 (P<0.01). Compared with the model group, Chufeng Yisuntang, p38 MAPK inhibitor, and the combination down-regulated the protein levels of p38 MAPK, Bax, and Caspase-3 (P<0.01), while up-regulating the protein level of Bcl-2 (P<0.01). Compared with the Chufeng Yisuntang group, the combination group exhibited decreased protein levels of p38 MAPK, Bax, and Caspase-3 (P<0.01) and increased protein level of Bcl-2 (P<0.01). Real-time PCR revealed that compared with the control group, the model group exhibited upregulated mRNA levels of p38 MAPK, Bax, and Caspase-3 (P<0.01), and downregulated mRNA level of Bcl-2 (P<0.01). Compared with the model group, Chufeng Yisuntang, p38 MAPK inhibitor, and the combination down-regulated the mRNA levels of p38 MAPK, Bax, and Caspase-3 (P<0.01), while up-regulating the mRNA level of Bcl-2 (P<0.05, P<0.01). Compared with the Chufeng Yisuntang group, the combination group exhibited decreased mRNA levels of p38 MAPK, Bax, and Caspase-3 expression (P<0.05, P<0.01) and increased mRNA level of Bcl-2 (P<0.01). ConclusionChufeng Yisuntang may partially protect against PM2.5-induced corneal injury by inhibiting the ROS/p38 MAPK pathway, enhancing antioxidant defense, and reducing epithelial apoptosis.
8.Mechanism of Action of Kaixinsan in Ameliorating Alzheimer's Disease
Xiaoming HE ; Xiaotong WANG ; Dongyu MIN ; Xinxin WANG ; Meijia CHENG ; Yongming LIU ; Yetao JU ; Yali YANG ; Changbin YUAN ; Changyang YU ; Li ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):20-29
ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Encyclopedia of Traditional Chinese Medicine(ETCM) databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards, Online Mendelian Inheritance in Man(OMIM), TTD, PharmGKB, and DrugBank databases were used to obtain the relevant targets of AD. The intersection (common targets) of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken, and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction(PPI) network. The CytoNCA plugin within Cytoscape was used to screen out the core targets, and the Metascape platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2, and AutoDock Vina was used for molecular docking. Scopolamine (SCOP) was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control (CON) group (0.9% NaCl, n=8), model (SCOP) group (3 mg·kg-1·d-1, n=8), positive control group (3 mg·kg-1·d-1 of SCOP+3 mg·kg-1·d-1 of Donepezil, n=8), and Kaixinsan group (3 mg·kg-1·d-1 of SCOP+6.5 g·kg-1·d-1 of Kaixinsan, n=8). Mice in each group were administered with 0.9% NaCl, Kaixinsan, or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to determine the serum acetylcholine (ACh) and acetylcholinesterase (AChE) contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3(STAT3) and nuclear transcription factor(NF)-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained, and 578 potential targets (common targets) of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol, gijugliflozin, etc.. Potential core targets were STAT3, NF-κB p65, et al. GO functional enrichment analysis obtained 3 124 biological functions, 254 cellular building blocks, and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways, mainly involving cancer-related pathways, TRP pathway, cyclic adenosine monophosphate(cAMP) pathway, and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65, STAT3, and other targets involved in the NF-κB signaling pathway.
9.Clinical Efficacy of Modified Huangqi Chifengtang in Treatment of IgA Nephropathy Patients and Exploration of Dose-effect Relationship of Astragali Radix
Xiujie SHI ; Meiying CHANG ; Yue SHI ; Ziyan ZHANG ; Yifan ZHANG ; Qi ZHANG ; Hangyu DUAN ; Jing LIU ; Mingming ZHAO ; Yuan SI ; Yu ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):9-16
ObjectiveTo explore the dose-effect relationship and safety of high, medium, and low doses of raw Astragali Radix in the modified Huangqi Chifengtang (MHCD) for treating proteinuria in immunoglobulin A (IgA) nephropathy, and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy, diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity, were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo, while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix (60, 30, 15 g). Each group contained 30 patients, and the treatment period was 12 weeks. Changes in 24-hour urinary protein (24 hUTP), traditional Chinese medicine (TCM) syndrome scores, effective rate, and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment, 24 hUTP significantly decreased in the high, medium, and low-dose groups, as well as the control group (P<0.05, P<0.01). The TCM syndrome scores in the high, medium, and low-dose groups also significantly decreased (P<0.01). Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium, low-dose, and control groups (P<0.05, P<0.01), and the 24 hUTP in the medium-dose group was significantly lower than in the control group (P<0.05). The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups (P<0.05, P<0.01). The total effective rates for proteinuria in the high, medium, low-dose, and control groups were 92.59% (25/27), 85.19% (23/27), 60.71% (17/28), and 57.14% (16/28), respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups (χ2=13.185, P<0.05, P<0.01). The effective rates for TCM syndrome scores in the high, medium, low-dose, and control groups were 88.89% (24/27), 81.48% (22/27), 71.43% (20/28), and 46.43% (13/28), respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group (χ2=14.053, P<0.01). Compared with pre-treatment values, there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However, eGFR significantly decreased in the low-dose and control groups after treatment (P<0.05), and serum creatinine levels increased significantly in the control group (P<0.05). No statistically significant differences were observed in urea nitrogen, uric acid, albumin, total cholesterol, triglycerides, liver function, and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high, medium, and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.
10.Potential application of liver organoids in liver disease models and transplantation therapy
Weibo YUAN ; Chan LIU ; Limei YU
Chinese Journal of Tissue Engineering Research 2025;29(8):1684-1692
BACKGROUND:Liver organoids are of great significance to elucidate the exact pathological mechanism of liver diseases and the treatment of liver diseases. OBJECTIVE:To summarize the basic research in this field at home and abroad,review the important research progress in the construction of liver organoids,disease modeling and transplantation therapy,and discuss the application prospect of combined tissue engineering technology of liver organoids. METHODS:The relevant articles included in PubMed and CNKI databases were searched.The English and Chinese search terms were"liver,organoids,liver diseases."The main search time was from April 2018 to April 2024.Duplicate literature was excluded by manual reading.Finally,94 articles were included for review and analysis. RESULTS AND CONCLUSION:The seed cells constructed by liver organoids are mainly concentrated in adult cells and pluripotent stem cells,which promote the generation of organoids by assisting various cytokines to participate in signal guidance and providing 3D microenvironment by extracellular matrix.However,the overall maturity is not high,which is expected to improve this problem by combining tissue engineering technology.In vitro disease modeling is mainly studied in the field of simple diseases and single-gene genetic diseases.Organoids highly retain patient genetic characteristics,and it is expected to simulate more complex liver diseases and clarify deeper pathological mechanisms by combining CRISPR-Cas9 gene correction and other emerging technologies.In vivo transplantation treatment,liver organoids can be safely and effectively implanted,showing amazing liver function replacement potential,tissue regeneration ability,and may also be combined with other tissue engineering materials to achieve therapeutic purposes.

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