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.Effects of Yishen paidu formula on renal fibrosis in rats with chronic renal failure by regulating the ROS/TXNIP/NLRP3 pathway
Li FENG ; Bowen PENG ; Bin PENG ; Xue FENG ; Shuangyi ZHU ; Wei XIONG ; Xi HU ; Xiaohui SUN
China Pharmacy 2026;37(2):174-179
OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure (CRF) through the reactive oxygen species (ROS)/thioredoxin-interacting protein (TXNIP)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) pathway. METHODS Rats were randomly divided into control group, model group, Yishen paidu formula low-dose (Yishen paidu formula-L) group, Yishen paidu formula high-dose (Yishen paidu formula- H) group, Yishen paidu formula-H+pcDNA-NC group, and Yishen paidu formula-H+ pcDNA-TXNIP group, with 10 rats in each group. Except for control group, all other rats were fed a diet containing 0.5% adenine to establish a CRF model; the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein, once daily, for 8 consecutive weeks. After the last administration, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), ROS, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β were measured in each group. Pathological changes in renal tissue were observed, and the protein expression levels of Collagen Ⅲ, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group, the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr, BUN, ROS, MDA, TNF- α, IL-6 and IL-1β, and the protein expressions of Collagen Ⅲ, α-SMA, TGF-β1, TXNIP and NLRP3 were significantly decreased, while SOD levels were significantly increased (P<0.05). Moreover, the changes were more pronounced in the Yishen paidu formula-H group (P<0.05). Compared with Yishen paidu formula-H+pcDNA-NC group, above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly (P<0.05). CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.
4.Interpretation of research progress on EGFR-mutant non-small cell lung cancer at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting
Xuxu ZHANG ; Jiahe LI ; Jipeng ZHANG ; Wei LI ; Wen LIU ; Bo BAO ; Qiang LU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):19-29
The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting was held in Chicago. At the meeting, researches on the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) once again took the spotlight. Combination therapy strategies have demonstrated the potential to overcome resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI) and prolong survival. Meanwhile, progress has also been made in individualized treatment strategies for young patients and those with fibrotic interstitial lung disease. However, the complexity of resistance mechanisms, special treatment considerations for different populations, and the impact of socioeconomic factors on treatment accessibility remain challenges in the field of EGFR-mutant NSCLC treatment. In the future, it is necessary to further explore more effective treatment regimens and expand the accessibility of precision medicine to maximize patient benefits.
5.Association between insufficient sleep and depressive symptoms among junior and senior high school students
LI Minmin, ZHANG Zhankui, MI Baibing, ZHAO Jingjun, WANG Yanxin, SHI Wei
Chinese Journal of School Health 2026;47(2):241-245
Objective:
To analyze the association between insufficient sleep and score of depressive symptoms among junior and senior high school students, so as to provide a scientific reference for targeted early intervention measures of adolescents depressive symptoms.
Methods:
From September to November 2023, a stratified cluster random sampling method was used to select 96 080 junior and senior high school students from 409 schools in 113 districts and counties in Shaanxi Province. A questionnaire survey was conducted using the 2023 Shaanxi Provincial Common Student Diseases and Health Influencing Factors Survey Form, and their height and weight were measured. Propensity score (PS) matched (1∶1) analysis was used to match participants with insufficient sleep to those sufficient sleep students. Through the gradual correction of the confounders, three multilevel linear models were established to analyze the association between insufficient sleep and depressive symptoms score, and subgroup analysis was conducted afterward.
Results:
A total of 70 135 (73.00%) students had insufficient sleep. After PS matching, 25 894 pairs were matched. Before PS matching, after adjusting for gender, educational stage, region, adolescent characteristics, boarding status, smoking, alcohol consumption, outdoor activities and body mass index grouping, linear regression analysis results showed that compared with students who got adequate sleep, students who lacked sleep had an increase of 1.39 scores ( B=1.39, 95%CI =1.28-1.51) in depressive symptoms; after PS matching, students with insufficient sleep got an increase of 1.32 scores ( B=1.32, 95%CI =1.17- 1.45 ) in depressive symptoms score compared with those who had adequate sleep (both P <0.05).
Conclusions
The insufficient sleep is associated with the increase of the depressive symptoms score of junior and senior high school students. It is recommended that junior and senior high school students should keep a good sleeping habit, so as to reduce the prevalence of depressive symptoms.
6.Interpretation of advances in the treatment of non-small cell lung cancer at the 2025 World Conference on Lung Cancer (WCLC)
Bo BAO ; Jiayu LU ; Wen LIU ; Xuxu ZHANG ; Jiahe LI ; Jipeng ZHANG ; Wei LI ; Qiang LU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):218-230
The 26th World Conference on Lung Cancer (WCLC) was held in Barcelona during September 6-9, 2025. As the world's largest and most influential academic meeting in the field of lung cancer, this year's congress unveiled long-term follow-up data from several pivotal studies and significant advances in novel therapeutic strategies. In the realm of targeted therapy, a next-generation combination strategy has been established as the new standard of care for the first-line treatment of patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), demonstrating a significant improvement in overall survival. In immunotherapy, novel combination regimens have not only addressed the therapeutic challenge of acquired resistance to EGFR targeted therapies, but also shown clear long-term survival benefits in both the perioperative and locally advanced settings. These findings pave the way for shifting the treatment paradigm to earlier stages for patients with NSCLC. Antibody-drug conjugates have made remarkable strides in this field. They have shown outstanding efficacy in patients with specific resistance mutations and those with brain metastases, and have also demonstrated immense potential in treating patients with HER2-aberrant lung cancer and broader NSCLC populations. This offers new therapeutic options for patients with refractory lung cancer.However, significant challenges remain, including the heterogeneity of resistance mechanisms, the selection of optimal treatment regimens, and management strategies for special populations. Future research should focus on identifying novel precision biomarkers and optimizing therapeutic strategies to ultimately improve clinical outcomes for all patients with lung cancer.
7.Knowledge map and visualization analysis of pulmonary nodule/early-stage lung cancer prediction models
Yifeng REN ; Qiong MA ; Hua JIANG ; Xi FU ; Xueke LI ; Wei SHI ; Fengming YOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):100-107
Objective To reveal the scientific output and trends in pulmonary nodules/early-stage lung cancer prediction models. Methods Publications on predictive models of pulmonary nodules/early lung cancer between January 1, 2002 and June 3, 2023 were retrieved and extracted from CNKI, Wanfang, VIP and Web of Science database. CiteSpace 6.1.R3 and VOSviewer 1.6.18 were used to analyze the hotspots and theme trends. Results A marked increase in the number of publications related to pulmonary nodules/early-stage lung cancer prediction models was observed. A total of 12581 authors from 2711 institutions in 64 countries/regions published 2139 documents in 566 academic journals in English. A total of 282 articles from 1256 authors were published in 176 journals in Chinese. The Chinese and English journals which published the most pulmonary nodules/early-stage lung cancer prediction model-related papers were Journal of Clinical Radiology and Frontiers in Oncology, respectively. Chest was the most frequently cited journal. China and the United States were the leading countries in the field of pulmonary nodules/early-stage lung cancer prediction models. The institutions represented by Fudan University had significant academic influence in the field. Analysis of keywords revealed that multi-omics, nomogram, machine learning and artificial intelligence were the current focus of research. Conclusion Over the last two decades, research on risk-prediction models for pulmonary nodules/early-stage lung cancer has attracted increasing attention. Prognosis, machine learning, artificial intelligence, nomogram, and multi-omics technologies are both current hotspots and future trends in this field. In the future, in-depth explorations using different omics should increase the sensitivity and accuracy of pulmonary nodules/early-stage lung cancer prediction models. More high-quality future studies should be conducted to validate the efficacy and safety of pulmonary nodules/early-stage lung cancer prediction models further and reduce the global burden of lung cancer.
8.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
9.Influencing factors for autism spectrum disorder in Chinese children: a meta analysis
CHEN Xi ; YANG Hongsheng ; LI Wei ; ZHAI Rui ; JIANG Yanlin ; WANG Junhong
Journal of Preventive Medicine 2025;37(2):181-188
Objective:
To systematically evaluate the influencing factors for autism spectrum disorder (ASD) in Chinese children, so as to provide the evidence for risk prediction and intervention of ASD.
Methods:
The publications pertaining to the influencing factors for ASD in Chinese children were retrieved from CNKI, Wanfang Data, VIP, PubMed and Embase database from inception to August 2024. A meta-analysis was performed using R package version 4.4.1. Sensitivity analysis was performed using the "leave-one-out" evaluation procedure. Publication bias was assessed using Egger regression test.
Results:
A total of 38 high-quality articles out of 9 015 articles were finally included, covering 149 607 individuals, with 5 974 cases of ASD. The meta-analysis showed that demographic factors including family history of related diseases (OR=14.958), maternal age of ≥35 years (OR=2.287) and parental history of hazardous occupations (OR=3.511); pregnancy-related factors including history of abortion (OR=5.832), no folate supplementation before and during pregnancy (OR=4.566), tobacco exposure before and during pregnancy (OR=2.596), history of other adverse exposures before and during pregnancy (OR=3.533), history of infectious diseases during pregnancy (OR=3.753), history of non-infectious diseases during pregnancy (OR=2.563), psychological problems during pregnancy (OR=3.864), history of medication during pregnancy (OR=6.651), adverse environmental exposures during pregnancy (OR=3.754), severe pregnancy reactions (OR=5.082), abnormal perinatal period (OR=2.987), cesarean delivery (OR=1.659), other perinatal adverse factors (OR=3.856), history of neonatal asphyxia (OR=2.792) and neonatal jaundice (OR=3.687); parenting factors including non-exclusive breastfeeding (OR=2.510), early/excessive screen exposure (OR=3.589) and feeding problems (OR=3.113); and individual factors including being male (OR=3.333) and history of convulsions/epilepsy (OR=7.035) were influencing factors for ASD in Chinese children.
Conclusions
The prevalence of ASD in Chinese children is primarily associated with 23 influencing factors, including family history of related diseases, history of abortion, no folate supplementation before and during pregnancy, medication during pregnancy, early/excessive screen exposure and history of convulsions/epilepsy.
10.Gao Jiansheng's Experience in Differentiating and Treating Herpes Simplex Keratitis Based on the Theory of Hidden Pathogens
Xi CHEN ; Yina CHEN ; Xiaonan YANG ; Danyu LI ; Wei YANG
Journal of Traditional Chinese Medicine 2025;66(5):448-452
This paper summarizes Professor Gao Jiansheng's clinical experience in treating herpes simplex keratitis (HSK) based on the theory of hidden pathogens. It is believed that the core pathogenesis of HSK involves deficiency of vital qi and the internal presence of pathogenic factors. In the early stage, the pathogenesis is characterized by lung and spleen qi deficiency and invasion of external pathogens. In the middle stage, pathogenesis worsens due to latent pathogens damaging the vital qi and spleen deficiency with dampness. In the late stage, kidney yang deficiency and lingering pathogenic toxins are the root cause of recurrent attacks. In clinical practice, it is recommended to strengthen and protect the vital qi. In the early stage, the Modified Yupingfeng Powder (玉屏风散) is used. In the middle stage, the Modified Linggui Zhugan Decoction (苓桂术甘汤) is used. In the late stage, a self-formulated Modified Bushen Tuodu Fomulation (补肾托毒方) is applied. Additionally, herbs of tonifying qi and strengthening the exterior are used throughout the treatment to reduce recurrence.


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