1.Exploring Mechanism of Yiqi Huoxue Jiedu Formula in Alleviating Immune Cell Exhaustion in Sepsis Based on Transcriptomics and Metabolomics
Rui CHEN ; Qiusha PAN ; Kaiqiang ZHONG ; Shuqi MA ; Wei HUANG ; Jiahua LAI ; Ruifeng ZENG ; Xiaotu XI ; Jun LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):109-118
ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula(YHJF) on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated, model, low-dose YHJF(4.1 g·kg-1), and high-dose YHJF(8.2 g·kg-1) groups. Except for the sham-operated group, a cecal ligation and puncture(CLP) procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses, while the sham-operated and model groups received an equal volume of physiological saline. After the intervention, the 7-day survival rate of each group was recorded, and spleen samples were collected 72 h post-intervention, and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP) nick end labeling(TUNEL) staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the levels of interleukin(IL)-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes(DEGs) and differential metabolites in the spleen, followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction(Real-time PCR), flow cytometry, and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice(P0.05). Compared with the sham-operated group, the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling, with markedly elevated peripheral serum IL-4 and IL-10 levels(P0.01). Compared with the model group, the high-dose YHJF group showed a reduction in apoptosis of spleen cells, an increase in the spleen index, and a significant decrease in peripheral serum IL-4 and IL-10 levels(P0.05). Spleen transcriptomics identified 255 DEGs between groups, potentially serving as intervention targets for YHJF. Gene Ontology(GO) enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer(NK) cell-mediated positive immune regulation, cell killing, cytokine production, positive regulation of innate immune cells, and interferon production. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear transcription factor-κB(NF-κB) signaling pathway. Protein-protein interaction(PPI) network analysis identified CD160, granzyme B(GZMB), and chemokine ligand 4(CCL4) as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention, and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism, arachidonic acid metabolism, glycosylphosphatidylinositol(GPI) anchor biosynthesis, linoleic acid metabolism, and α-linolenic acid metabolism pathways. Verification results showed that, compared with the sham-operated group, the model group exhibited significantly elevated CD160 mRNA expression level in the spleen, along with markedly decreased CCL4 and GZMB mRNA expression, and had a significant increase in CD160 expression on the surface of natural killer T(NKT) cells in the spleen(P0.01). Compared with the model group, the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen, a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group, CD160 expression on the surface of splenic NKT cells in the model group was significantly increased(P0.01), while high-dose YHJF intervention significantly reduced CD160 expression(P0.01). ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160, and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.
2.Exploring Mechanism of Yiqi Huoxue Jiedu Formula in Alleviating Immune Cell Exhaustion in Sepsis Based on Transcriptomics and Metabolomics
Rui CHEN ; Qiusha PAN ; Kaiqiang ZHONG ; Shuqi MA ; Wei HUANG ; Jiahua LAI ; Ruifeng ZENG ; Xiaotu XI ; Jun LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):109-118
ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula(YHJF) on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated, model, low-dose YHJF(4.1 g·kg-1), and high-dose YHJF(8.2 g·kg-1) groups. Except for the sham-operated group, a cecal ligation and puncture(CLP) procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses, while the sham-operated and model groups received an equal volume of physiological saline. After the intervention, the 7-day survival rate of each group was recorded, and spleen samples were collected 72 h post-intervention, and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP) nick end labeling(TUNEL) staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the levels of interleukin(IL)-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes(DEGs) and differential metabolites in the spleen, followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction(Real-time PCR), flow cytometry, and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice(P0.05). Compared with the sham-operated group, the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling, with markedly elevated peripheral serum IL-4 and IL-10 levels(P0.01). Compared with the model group, the high-dose YHJF group showed a reduction in apoptosis of spleen cells, an increase in the spleen index, and a significant decrease in peripheral serum IL-4 and IL-10 levels(P0.05). Spleen transcriptomics identified 255 DEGs between groups, potentially serving as intervention targets for YHJF. Gene Ontology(GO) enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer(NK) cell-mediated positive immune regulation, cell killing, cytokine production, positive regulation of innate immune cells, and interferon production. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear transcription factor-κB(NF-κB) signaling pathway. Protein-protein interaction(PPI) network analysis identified CD160, granzyme B(GZMB), and chemokine ligand 4(CCL4) as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention, and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism, arachidonic acid metabolism, glycosylphosphatidylinositol(GPI) anchor biosynthesis, linoleic acid metabolism, and α-linolenic acid metabolism pathways. Verification results showed that, compared with the sham-operated group, the model group exhibited significantly elevated CD160 mRNA expression level in the spleen, along with markedly decreased CCL4 and GZMB mRNA expression, and had a significant increase in CD160 expression on the surface of natural killer T(NKT) cells in the spleen(P0.01). Compared with the model group, the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen, a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group, CD160 expression on the surface of splenic NKT cells in the model group was significantly increased(P0.01), while high-dose YHJF intervention significantly reduced CD160 expression(P0.01). ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160, and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.
3.A bibliometric and visual analysis of the literature published in the journal of Organ Transplantation since its inception
Xi CAO ; Tao HUANG ; Qiwei YANG ; Lin YU ; Xiaowen WANG ; Wenfeng ZHU ; Haoqi CHEN ; Ning FAN ; Genshu WANG
Organ Transplantation 2026;17(1):133-142
Objective To systematically analyze the literature characteristics of Journal of Organ Transplantation since its inception. Methods Using the China National Knowledge Infrastructure (CNKI) academic journal full-text database as the data source, all articles published in the Journal of Organ Transplantation from January 2010 to August 2025 were retrieved. After excluding non-academic papers, a total of 1 568 research papers were included. R language 4.3.0, Bibliometrix package 3.2.1, and Citespace software were used to analyze the number of publications, publishing institutions, authors, keywords and other aspects. Results The number of publications in Journal of Organ Transplantation increased from an average of 82 articles per year in the early years after its inception to 113 articles per year in recent years, a growth of 37.8%. The geographical distribution of publishing institutions covers 32 provinces, cities and autonomous regions nationwide, mainly concentrated in the South China, East China and North China regions, and has now basically covered the central and western regions in recent years. The author collaboration network includes 45 authors distributed across 7 major collaboration clusters, forming a stable multi-level national research system centered on key university-affiliated hospitals. The high-frequency keywords are dominated by "liver transplantation" (425 times) and "kidney transplantation" (396 times). The theme evolution shows a clear three-stage characteristic: initially focusing on clinical technology application, deepening to immune mechanism exploration in the middle stage, and recently (since 2022) focusing on cutting-edge research areas such as xenotransplantation. Conclusions Journal of Organ Transplantation has witnessed the rapid development of China's organ transplantation cause, fully reflecting the research status and trends in China's organ transplantation field, and has provided an important platform for the future development and international cooperation in China's organ transplantation field.
4.Effect and Mechanism of Schisandrae Chinensis Fructus Lignans on Behavior of Schizophrenic Mice
Jiaqi LI ; Xi CHEN ; Siwei WANG ; Qi WANG ; Yiting LIU ; Ziyan GUO ; Zilong LUN ; Chengyi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):65-71
ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate (MK-801) in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank, model, positive drug, and low-, medium-, and high-dose (40, 80, 160 mg·kg-1, respectively) Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water, and the other groups were injected with 0.5 mg·kg-1 MK-801 to induce schizophrenia symptoms. Meanwhile, risperidone was injected at 0.2 mg·kg-1 in the positive drug group, and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test, open field test, forced swimming test, and water maze test. The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) in the brain and tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in peripheral blood were quantified by enzyme-linked immunosorbent assay (ELISA). The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining, and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 (SIRT1) and forkhead box protein O3a (FoxO3a) in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group, low, medium, and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities, total distance in the open field test, immobile time in the forced swimming test, and levels of TNF-α and NF-κB in peripheral blood (P<0.05), while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue (P<0.05). Compared with the model group, risperidone and low, medium, and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region, with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus (P<0.05). ConclusionTo sum up, Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.
5.Risk factors for type 2 diabetes mellitus with metabolic-associated fatty liver disease and their relationship with BMI management
Xi CHEN ; Jing ZHANG ; Yang LIU
Journal of Public Health and Preventive Medicine 2026;37(1):108-111
Objective To analyze the risk factors of type 2 diabetes mellitus (T2DM) with metabolic-associated fatty liver disease (MAFLD) and explore their relationship with BMI management. Methods A retrospective analysis was conducted of 310 patients with type 2 diabetes who underwent physical examinations at the 363 hospital between March 2023 and March 2025. Among these patients, those with MAFLD were counted. The risk factors of T2DM with MAFLD were analyzed by logistic regression analysis. The relationship between T2DM with MAFLD and BMI management was explored by Spearman correlation coefficient analysis. Results Compared with the non-MAFLD group, the levels of alanine aminotransferase (ALT), fasting insulin (I0), fasting blood glucose (G0), BMI, triglyceride (TG), aspartate aminotransferase (AST), and serum uric acid (SUA) were higher while the level of high-density lipoprotein cholesterol (HDL-C) was lower in the MAFLD group (P<0.05). Logistic regression analysis showed that BMI, SUA, I0, ALT, G0, and BMI control scale score were risk factors of T2DM with MAFLD (P<0.05). The score of BMI control scale of patients in the MAFLD group was higher than that in the non-MAFLD group (P<0.05). Correlation analysis indicated that T2DM with MAFLD was negatively correlated with BMI management (P<0.05). Conclusion BMI, SUA, I0, ALT, and G0 are all risk factors of T2DM with MAFLD. BMI management is negatively correlated with T2DM with MAFLD. Patients with T2DM should control BMI and blood glucose to reduce the occurrence of MAFLD.
6.Effects of baicalin on insulin resistance in rats with gestational diabetes mellitus and its mechanism
Kewei SHI ; Xi CHEN ; Xiaoyan ZHAO ; Bo YANG ; Yunchun LIU ; Yueyue GAO
China Pharmacy 2026;37(4):450-455
OBJECTIVE To investigate the effects of baicalin (BC) on insulin resistance in rats with gestational diabetes mellitus (GDM) and its underlying mechanism based on the adenosine monophosphate-activated protein kinase (AMPK)/suppressor of variegation 3-9 homolog 1 (SUV39H1)/histone H3 lysine 9 trimethylation (H3K9me3) axis. METHODS A GDM rat model was established by a combination of a high-fat diet and streptozotocin injection. The successfully modeled rats were divided into the GDM group, BC low-dose group, BC high-dose group, and high-dose of BC+AMPK inhibitor (Compound C) group, with 10 rats in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding drugs/normal saline intragastrically and/or intraperitoneally, once daily for 2 consecutive weeks. After the last administration, the levels of fasting blood glucose (FBG), pancreatic function indexes [fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISI)], blood lipid indexes (total cholesterol, triglyceride, low-density lipoprotein cholesterol), liver function indexes (alanine transferase, aspartate transferase, alkaline phosphatase), inflammatory indicators (C-reactive protein, interleukin-1β, interleukin-6), metabolic regulatory protein [complement-C1q/tumor necrosis factor-related protein 3 (CTRP3)], insulin sensitivity related factors [glucose transporter 4 (GLUT4), adiponectin], and oxidative stress indicators [superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA)] were measured. Pathological changes in liver tissue were observed, and the expressions of proteins related to the AMPK/SUV39H1/H3K9me3 axis in liver tissue were detected. RESULTS Compared with the GDM group, rats in the BC low- and high-dose groups showed varying degrees of improvement in pathological changes such as disordered cell arrangement, vacuolar degeneration, lipid deposition, and inflammatory cell infiltration in liver tissue. Their FBG and FINS levels, HOMA-IR, the levels of blood lipid indexes, liver function indexes, inflammatory indicators and MDA, and the expressions of SUV39H1 and H3K9me3 were significantly decreased or down-regulated, while metabolic regulatory protein, insulin sensitivity-related factors and AMPK protein phosphorylation levels were significantly increased ( P <0.05). The improvement was more significant in the BC high-dose group ( P <0.05). Compound C could significantly reverse the ameliorative effects of high-dose BC on the above quantitative indicators ( P <0.05). CONCLUSIONS BC can significantly reduce oxidative stress and inflammatory responses, increase serum levels of CTRP3, GLUT4 and adiponectin, thereby improving insulin resistance in GDM rats. These effects may be related to the activation of AMPK and inhibition of SUV39H1-mediated H3K9me3 modification.
7.Clinical doctor-patient shared decision-making: the “collision” between Western theories and Chinese culture
Mengnan LI ; Yuanyuan YAN ; Guang FU ; Xi CHEN ; Wenjuan MO
Chinese Medical Ethics 2026;39(1):100-104
This paper reviewed the development history of doctor-patient shared decision-making (SDM) at home and abroad, emphasizing the importance of cross-cultural analysis in constructing a Chinese doctor-patient SDM model. It also delved into the relationship between Western “individualistic” sociocultural values and doctor-patient SDM, as well as the influence of China’s “collectivist” sociocultural values on doctor-patient SDM, revealing significant disparities in doctor-patient SDM models under distinct sociocultural contexts. Although the doctor-patient SDM theory in China originated from the West, this theory requires profound “collision” and adaptation with local Chinese culture to form a localized theory suited to China’s national conditions. Through cross-cultural adaptation and integrating China’s familism tradition and medical ethics concepts, the future construction of the doctor-patient SDM model in China should emphasize family members’ involvement and seek cultural balance to facilitate its widespread application in clinical practice.
8.Construction and Evaluation of "Constitution-disease-syndrome" Trinity Model for Rodents with Qi Deficiency
Yasheng DENG ; Jiang LIN ; Yujiang XI ; Qian ZHOU ; Yanping FAN ; Wenyue LI ; Yonghui LIU ; Zhaobing NI ; Qiu CHEN ; Xi MING
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):274-284
The theory of constitution in traditional Chinese medicine (TCM) has emerged as a new discipline in recent years. Constitution plays a vital role in the onset,progression,transformation,and prognosis of diseases. At present,some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation",in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology,onset,pathogenesis,syndrome differentiation,and treatment. Against this background,the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution,aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models,thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions,diseases,and syndromes,but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods,the study evaluates the model's validity,reliability,and practicality,with the aim of opening new avenues for future research in TCM and promoting the development of the field.
9.Construction and Evaluation of "Constitution-disease-syndrome" Trinity Model for Rodents with Qi Deficiency
Yasheng DENG ; Jiang LIN ; Yujiang XI ; Qian ZHOU ; Yanping FAN ; Wenyue LI ; Yonghui LIU ; Zhaobing NI ; Qiu CHEN ; Xi MING
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):274-284
The theory of constitution in traditional Chinese medicine (TCM) has emerged as a new discipline in recent years. Constitution plays a vital role in the onset,progression,transformation,and prognosis of diseases. At present,some clinical scholars have adopted a novel diagnostic and treatment model of "constitution differentiation-disease identification-syndrome differentiation",in which constitution is regarded as a core element throughout the diagnostic and therapeutic process. Constitution is closely associated with etiology,onset,pathogenesis,syndrome differentiation,and treatment. Against this background,the construction of animal models based on constitution holds far-reaching significance for advancing clinical research. This paper focuses on the construction and evaluation of rodent models with Qi-deficiency constitution,aiming to explore how to further induce Qi-deficiency syndromes and related disease states on the basis of Qi-deficiency constitution models,thereby developing an integrated animal model that embodies the trinity of "constitution-disease-syndrome". The establishment of this model not only provides a solid experimental foundation for the development of new therapies and drugs in TCM targeting specific constitutions,diseases,and syndromes,but also greatly promotes the modernization and scientific advancement of TCM theory. By comprehensively applying multidisciplinary technologies and methods,the study evaluates the model's validity,reliability,and practicality,with the aim of opening new avenues for future research in TCM and promoting the development of the field.
10.Impact of number of positive regional lymph nodes in N1 stage on the prognosis of patients with non-small cell lung cancer: A propensity score matching study
Dandan LIU ; Jiachen WANG ; Lidan CHANG ; Jia CHEN ; Ranran KONG ; Shiyuan LIU ; Minxia ZHU ; Jiantao JIANG ; Shaomin LI ; Zhengshui XU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):63-71
Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.


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