1.Impact of optimized varicella vaccination strategy on varicella incidence among nursery children in Shenzhen
Chinese Journal of School Health 2026;47(5):728-731
Objective:
To analyze the epidemiological characteristics of varicella among nursery children in Shenzhen from 2015 to 2024, and to evaluate the impact of optimizing varicella vaccine (VarV) immunization strategies on varicella incidence.
Methods:
Varicella incidence data for nursery children in Shenzhen from 2015 to 2024 were obtained from the China Disease Prevention and Control Information System. The study period was divided into three phases:one dose self pay VarV (January 2015 to October 2017), two dose self pay VarV (November 2017 to October 2019), and two dose free VarV (November 2019 to December 2024). Interrupted time series (ITS) analysis was conducted to assess changes in the level and trend of varicella incidence associated with each phase of policy implementation.
Results:
A total of 27 517 varicella cases was reported among nursery children from 2015 to 2024, with an average annual incidence of 514.01/100 000. During the same period, 136 clustered outbreaks were reported in nursery institutions, involving a cumulative total of 1 091 cases. ITS analysis showed that during the self pay 1 dose stage, the varicella incidence among nursery children showed an upward trend, with an average monthly increase of 2.58/100 000 (95% CI =2.21/ 100 000 -2.95/100 000, P <0.01). After the implementation of the self pay 2 dose strategy, the incidence decreased, with a change in incidence of -26.12/100 000 (95% CI =-37.30/100 000 to -14.94/100 000) and a change in slope of -2.65/100 000 (95% CI = -3.38/100 000 to -1.93/100 000)(all P <0.01). After the implementation of the free 2 dose strategy, the incidence decreased further, with a change in incidence of -40.03/100 000 (95% CI =-50.39/100 000 to -29.66/100 000, P <0.01) and a change in slope of -0.56/100 000 (95% CI =-1.20/100 000-0.08/100 000, P =0.09).
Conclusion
The gradual optimization of the VarV vaccination strategy in Shenzhen from self pay 1 dose to free 2 dose has significantly reduced the varicella incidence among nursery children, demonstrating good short term control and long term intervention effectiveness.
2.Clinical Efficacy of Janus Kinase Inhibitors in Combination with Chinese Herbal Medicine for Rheumatoid Arthritis:A Retrospective Study and A Meta-analysis
Chenguang ZHAN ; Shengqin YANG ; Xin LI ; Yu WEN ; Peng ZHANG ; Xingrui YAN ; Haifang DU ; Maojie WANG ; Xiaodong WU ; Liyan MEI ; Xiumin CHEN ; Yanlin LI ; Runyue HUANG
Journal of Traditional Chinese Medicine 2026;67(5):534-543
ObjectiveTo evaluate the efficacy and safety of Janus kinase (JAK) inhibitors combined with Chinese herbal medicine (CHM) in treating rheumatoid arthritis (RA). MethodsClinical data from 169 RA patients were retrospectively collected. Among them, 71 cases received JAK inhibitors as the control group, while 98 cases received JAK inhibitors plus CHM as the observation group, both treated for 24 weeks. The rheumatoid factor (RF), cyclic citic peptide antibody (anti-CCP), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell count (WBC) were recorded before and after treatment. Databases including CNKI, Wanfang, VIP, PubMed and Web of Science were searched from inception till August 31st, 2025 for randomized controlled trials (RCTs) on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF, anti-CCP, ESR, CRP, 28-joint disease activity score (DAS28), overall clinical effective rate, and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment, ESR, CRP, and anti-CCP levels decreased in the observation group, while ESR and CRP levels decreased in the control group (P<0.05). Moreover, ESR and RF levels in the observation group were lower than those in the control group (P<0.05). A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF (MD=-8.97, 95%CI -15.01 to -2.94, P=0.004), CRP (MD=-3.34, 95%CI -3.82 to -2.86, P<0.001), ESR (MD=-5.33, 95%CI -7.98 to -2.69, P<0.001), and DAS28 score (MD=-0.54, 95%CI -0.74 to -0.34, P<0.001), as well as in improving the overall clinical effective rate (OR=4.53, 95%CI 2.55 to 8.03, P<0.001). No statistically significant differences were observed between groups in anti-CCP levels (SMD=-2.08, 95%CI -4.41 to 0.24, P=0.080) or incidence of adverse events (OR=0.93, 95%CI 0.55 to 1.57, P=0.790). ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA, contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.
3.Research progress on the role of macrophages in atherosclerosis
Wenxiu MA ; Li BAI ; Wen MA ; Tingting QI ; Haonan ZHANG ; Xuan WANG ; Xin ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(4):770-775
Atherosclerosis (AS) is a chronic and inflammatory vascular disease. Macrophages are common immune cells and play an important role in the development of AS. In recent years, research has found that the formation of AS plaques is closely related to pathological and physiological processes such as macrophage polarization, energy metabolism, and lipid phagocytosis. This review aims to summarize the mechanism of macrophages in the development of AS, and to explore potential therapeutic methods for delaying AS by regulating macrophages, providing new ideas for the treatment and research of AS.
4.DIA Proteomic Profiling on Staged Regulatory Effect of Tonifying Deficiency and Dredging Collaterals Method on Liver Fibrosis in Rats Based on Theory of "Zhu Ke Jiao"
Xin WANG ; Pengyu ZHU ; Li WEN ; Jibin LIU ; Aochun YUE ; Ziyi CHEN ; Jing ZHANG ; Li ZHU ; Quansheng FENG ; Cen JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):119-132
ObjectiveThis paper aims to investigate the differential mechanisms underlying the staged therapeutic effects of Qijia Rougan formula on liver fibrosis using proteomic technology. MethodsThe staged rat model of liver fibrosis was established by subcutaneous injection of carbon tetrachloride (CCl4) and olive oil. One hundred and four SD rats were randomized into thirteen groups:a normal group,a two-week model group,a four-week model group,a six-week model group,an eight-week model group,a two-week Qijia Rougan formula group,a four-week Qijia Rougan formula group,a six-week Qijia Rougan formula group,an eight-week Qijia Rougan formula group,a two-week compound Biejia Ruangan tablet group,a four-week Compound Biejia Ruangan Tablet group,a six-week Compound Biejia Ruangan Tablet group,and an eight-week compound Biejia Ruangan tablet group. After two weeks of drug intervention,liver tissue and abdominal aortic blood samples were collected from the rats for testing. Hematoxylin-eosin (HE) staining,Masson staining,and Picro Sirius red staining were used to observe pathological damage and collagen fiber deposition in liver tissues. Immunohistochemistry (IHC) was employed to detect the contents of fibrosis markers in liver tissues. The contents of liver function indicators in the serum were measured using a fully automated biochemical analyzer,and the levels of liver fibrosis indicators in the serum were assessed by enzyme-linked immunosorbent assay (ELISA). Liver tissues from the normal group,each model group,and each Qijia Rougan formula group were subjected to label-free quantitative proteomic analysis to identify differential proteins among the groups,with key proteins validated by Western blot. Finally,bioinformatics analysis was performed on the differential proteins. Results(1) The staged rat model of liver fibrosis constructed with CCl4 and olive oil showed pathological results at the 2nd,4th,6th,and 8th weeks of modeling that were consistent with the Metavir standards for the F1,F2,F3,and F4 stages. Compared with those in the normal control group,the protein expressions of α-smooth muscle actin (α-SMA) and Collagen Ⅰ were significantly increased in each stage (P<0.05). The levels of liver function indicators in the serum,including alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),direct bilirubin (DBIL),and total bilirubin (TBil) in each model group,were significantly elevated in each stage (P<0.01). The levels of liver fibrosis indicators in the serum,including procollagen Ⅲ peptide (PⅢP),type Ⅳ collagen(Ⅳ-C),hyaluronic acid (HA),and laminin (LN) in each model group,were significantly increased in each stage (P<0.05,P<0.01). This study successfully established a staged rat model of liver fibrosis. (2) Compared with the model groups at each stage,the administration groups showed a reduction in hepatocyte ballooning degeneration,a more orderly arrangement of hepatocytes,and a decrease of inflammatory cell infiltration. The blue-stained collagen fibers became significantly thinner and finer,with reduced and narrowed fibrous septa. The areas of collagen fibers and Picro Sirius red staining were reduced (P<0.05). The positive areas of α-SMA and Collagen Ⅰ expression were significantly decreased (P<0.05). The levels of ALT,AST,ALP,DBIL,and TBil in the rats of the model groups at each stage were significantly reduced (P<0.05,P<0.01). The levels of PⅢP,Ⅳ-C,HA,and LN in the rats of the model groups at each stage were significantly decreased (P<0.05). Among these,the improvements in all indicators were most significant in the F3 stage (P<0.01).(3) The proteomic results show that a total of 165 differential proteins exhibit a callback trend when comparing the model groups at four stages with the normal group,and when comparing the Qijia Rougan formula group with the model group. Western blot analysis reveals that the levels of NAD(P)H:quinone oxidoreductase 1 (NQO1),mitogen-activated protein kinase 1 (MAPK1),arginase 1 (Arg1),and glutathione S-transferase α1 (GSTA1) were consistent with the proteomic results. Bioinformatics results reveal that 165 differentially expressed proteins are enriched in multiple signaling pathways. Notably,signaling pathways such as drug metabolism-cytochrome P450,arginine biosynthesis,and the peroxisome proliferator-activated receptor (PPAR) signaling pathway were found to be closely associated with liver fibrosis,suggesting that the Qijia Rougan formula may exert its staged regulatory effects on liver fibrosis by regulating these pathways. ConclusionThe Qijia Rougan formula may achieve staged regulation of liver fibrosis by regulating drug metabolism-cytochrome P450,arginine biosynthesis,and the PPAR signaling pathway.
5.Analysis of follow-up and prognosis in pediatric rheumatic diseases associated with pulmonary embolism
Tong YUE ; Yuchun YAN ; Min KANG ; Jia ZHU ; Yingjie XU ; Dan ZHANG ; Ming LI ; Min WEN ; Feifei WU ; Jianming LAI
Chinese Journal of Pediatrics 2026;64(1):89-94
Objective:To explore the clinical characteristics, diagnosis and treatment strategies, and prognosis of pulmonary embolism (PE) complicating childhood rheumatic diseases.Methods:A retrospective case series study was performed on the demographic data, laboratory indicators, imaging features, treatment regimens, and follow-up data of 8 children with rheumatic diseases complicated by PE who were admitted to the Department of Rheumatology and Immunology, Capital Center for Children′s Health, Capital Medical University from January 2014 to October 2023.Results:Among the 8 children, there were 4 boys and 4 girls, with an age of 12.0 (7.5, 13.0) years. Among the primary diseases, there were 3 cases of systemic lupus erythematosus, 2 cases of Beh?et′s disease, 2 cases of Takayasu arteritis, and 1 case of antiphospholipid syndrome. All children developed PE during the active phase of the primary disease. PE was detected at the onset of the primary disease in 3 cases, and the median time from the diagnosis of the primary disease to the development of PE was 10.0 (6.0, 25.0) months in the remaining 5 cases. Fever was present in all 8 children, 4 cases were accompanied by chest tightness, dyspnea, etc., and 2 cases only presented with fever. Laboratory examinations revealed the following results: erythrocyte sedimentation rate was 42.0 (17.0, 78.0) mm/1 h, high-sensitivity C-reactive protein was 12.7 (2.6, 78.7) mg/L, white blood cell count was 9.6 (7.2, 18.7)×10 9/L; D-dimer was 2.3 (0.9, 6.2) mg/L; and hemoglobin was (109±16) g/L.Imaging examinations revealed that 5 cases had involvement of the bilateral lower pulmonary arteries, 5 cases had peripheral embolism, and 3 cases had central PE. Complications included 3 cases of deep vein thrombosis, 2 cases of intracranial venous sinus thrombosis, and 1 case of mild pulmonary hypertension.In terms of treatment, 7 cases received anticoagulation with heparin followed by warfarin. Immunomodulation was mainly based on glucocorticoids combined with immunosuppressants, and 4 cases were combined with biological agents. The follow-up time of 4.17 (1.75, 7.17) years, the time for complete absorption of PE was 10.5 (6.0, 18.0) months; all 8 children had no target events, with no recurrence or chronic thromboembolic pulmonary hypertension, and the pulmonary artery remodeling was good. Conclusions:PE complicating childhood rheumatic diseases is closely related to the activity of the primary disease. The clinical manifestations are insidious, with fever as the main symptom. Imaging examination is the key to diagnosis.Early adoption of heparin followed by warfarin anticoagulation and glucocorticoids combined with immunosuppressants and (or) biological agents to control the primary disease can achieve a favorable prognosis.
6.Effects of Huanglian Jiedutang on Neutrophil Infiltration in Brain of MCAO Mice via Regulation of Chemokine Expression in Exosomes
Haojia ZHANG ; Kai WANG ; Zijin SUN ; Chunyu WANG ; Wei SHAO ; Kunjing LIU ; Liyang DONG ; Dan CHEN ; Wenxiu XU ; Chuanzun WANG ; Wen WANG ; Changxiang LI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):42-53
ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion (MCAO) mice by regulating the expression of neutrophil-related chemokines in exosomes, thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups: Sham-operated group, MCAO model group, Huanglian Jiedutang group (6 g·kg-1), and Ginaton group (21.6 mg·kg-1), with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·(10 g)-1 for 7 consecutive days, while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days, MCAO surgery was performed. The distal and proximal ends of the right common carotid artery (CCA) were ligated, a small incision was made between the two ligatures, and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling, mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy, particle size analysis, and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase (MPO) in the brains of mice in each group. ResultsCompared with the sham-operated group, the model group showed decreased neurological function scores (P<0.01), obvious cerebral infarction (P<0.01), reduced cerebral blood flow (P<0.01), neuronal necrosis in the brain, and decreased numbers of Nissl bodies (P<0.01). The mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were significantly increased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were increased (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were elevated (P<0.01). Compared with the model group, the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores (P<0.05), reduced cerebral infarct volume (P<0.01), restored cerebral blood flow (P<0.01), reduced necrotic cells in the brain, and increased numbers of Nissl bodies (P<0.01). In the Huanglian Jiedutang group, the mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were decreased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were reduced (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were decreased (P<0.01). ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice, thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.
7.Correlation Analysis of Huanglian Jiedu Wan on Syndrome Improvement and Clinical Biomarkers of "Excess Heat-Toxicity" Based on Machine Learning Model
Qi LI ; Keke LUO ; Baolin BIAN ; Hongyu YU ; Mengxiao WANG ; Mengyao TIAN ; Wen XIA ; Yuan MA ; Xinfang ZHANG ; Pengyue LI ; Nan SI ; Hongjie WANG ; Yanyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):162-173
ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally, the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome, such as oral ulcers, sore throat, and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation, oxidative stress, and energy metabolism in the early phase, Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting (XGBoost) algorithm was used to develop a prediction model for main symptom classification, with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers, sore throat, and overall symptoms, with significant effects observed especially in sore throat and overall symptom analyses (P<0.01). Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement, were also called "heat-related biomarkers", including succinic acid, α-ketoglutaric acid, glycine, lactic acid, adenosine monophosphate (AMP), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and so on. Conversely, clinical biomarkers negatively correlated with symptom severity, were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan, including malic acid, fumaric acid, cis-aconitic acid, adrenocorticotropic hormone (ACTH), IL-1β, IL-4, IL-8, succinic acid, and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables, with importance scores of 0.081 and 0.080, respectively. After screening out 14 key variables and optimizing the parameters, model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables, confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established, achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.
8.Effects of Huanglian Jiedutang on Neutrophil Infiltration in Brain of MCAO Mice via Regulation of Chemokine Expression in Exosomes
Haojia ZHANG ; Kai WANG ; Zijin SUN ; Chunyu WANG ; Wei SHAO ; Kunjing LIU ; Liyang DONG ; Dan CHEN ; Wenxiu XU ; Chuanzun WANG ; Wen WANG ; Changxiang LI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):42-53
ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion (MCAO) mice by regulating the expression of neutrophil-related chemokines in exosomes, thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups: Sham-operated group, MCAO model group, Huanglian Jiedutang group (6 g·kg-1), and Ginaton group (21.6 mg·kg-1), with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·(10 g)-1 for 7 consecutive days, while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days, MCAO surgery was performed. The distal and proximal ends of the right common carotid artery (CCA) were ligated, a small incision was made between the two ligatures, and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling, mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy, particle size analysis, and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase (MPO) in the brains of mice in each group. ResultsCompared with the sham-operated group, the model group showed decreased neurological function scores (P<0.01), obvious cerebral infarction (P<0.01), reduced cerebral blood flow (P<0.01), neuronal necrosis in the brain, and decreased numbers of Nissl bodies (P<0.01). The mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were significantly increased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were increased (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were elevated (P<0.01). Compared with the model group, the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores (P<0.05), reduced cerebral infarct volume (P<0.01), restored cerebral blood flow (P<0.01), reduced necrotic cells in the brain, and increased numbers of Nissl bodies (P<0.01). In the Huanglian Jiedutang group, the mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were decreased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were reduced (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were decreased (P<0.01). ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice, thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.
9.Correlation Analysis of Huanglian Jiedu Wan on Syndrome Improvement and Clinical Biomarkers of "Excess Heat-Toxicity" Based on Machine Learning Model
Qi LI ; Keke LUO ; Baolin BIAN ; Hongyu YU ; Mengxiao WANG ; Mengyao TIAN ; Wen XIA ; Yuan MA ; Xinfang ZHANG ; Pengyue LI ; Nan SI ; Hongjie WANG ; Yanyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):162-173
ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally, the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome, such as oral ulcers, sore throat, and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation, oxidative stress, and energy metabolism in the early phase, Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting (XGBoost) algorithm was used to develop a prediction model for main symptom classification, with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers, sore throat, and overall symptoms, with significant effects observed especially in sore throat and overall symptom analyses (P<0.01). Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement, were also called "heat-related biomarkers", including succinic acid, α-ketoglutaric acid, glycine, lactic acid, adenosine monophosphate (AMP), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and so on. Conversely, clinical biomarkers negatively correlated with symptom severity, were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan, including malic acid, fumaric acid, cis-aconitic acid, adrenocorticotropic hormone (ACTH), IL-1β, IL-4, IL-8, succinic acid, and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables, with importance scores of 0.081 and 0.080, respectively. After screening out 14 key variables and optimizing the parameters, model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables, confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established, achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.
10.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.


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