1.Expert Consensus on Clinical Application of Qidong Yixin Oral Liquid
Changkuan FU ; Xiaochang MA ; Mingjun ZHU ; Yue DENG ; Hongxu LIU ; Mingxue ZHANG ; Ying CHEN ; Yan ZHOU ; Ling ZHANG ; Jianhua FU ; Wei YANG ; Yu'er HU ; Ming CHEN ; Yanming XIE ; Yuanyuan LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):147-158
The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis (VMC). It has the functions of tonifying Qi, nourishing the heart,calming the mind, and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However,the understanding of its efficacy evidence, advantageous aspects, dosage and administration, and medication safety remains insufficient in clinical practice. Therefore,the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid (hereinafter referred to as consensus) was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine,successively completing multiple tasks such as the consensus project initiation,determination of clinical problems,evidence search and evaluation,formation of recommendation opinions and consensus suggestions,solicitation of opinions,peer review, submission for review and release, and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions,clarifying the clinical positioning,efficacy advantages,syndrome differentiation,dosage and administration,combination therapy,timing of medication,adverse reactions,contraindications, and precautions of Qidong Yixin oral liquid,indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease,providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23, 2024. Standard number:GSCACM-376-2024.
2.Ancient and Modern Documentation of Classic Formula Sangjuyin
Xiaofang WANG ; Lyuyuan LIANG ; Jialei CAO ; Ziming XU ; Wangju ZHOU ; Yiping WANG ; Yujie CHANG ; Ruiting SU ; Yihan LI ; Jingwen LI ; Bingqi WEI ; Bingxiang MA ; Wenli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):200-207
Sangjuyin, as a pungent and cooling agent with precise therapeutic effect, is a classic pungent formula for cooling relief of the epidermis, which is highly respected by medical practitioners. This formula is from the Wenbing Tiaobian written by WU Jutong in the Qing dynasty, on the basis of which subsequent medical practitioners have made additions and subtractions to apply it. The authors used the bibliometric method to systematically organize the medical books from the Qing dynasty and the Republic of China and modern literature to analyze the composition, concoction, decoction, efficacy, and previous and modern application of Sangjuyin. After examination, the drug base of this formula is basically clear. Armeniacae Semen Amarum is the dried mature seeds of Armeniaca vulgaris, family Rosaceae. Forsythiae Fructus is the dried fruit of Forsythia suspensa, family Mulleinaceae. Menthae Haplocalycis Herba is the dried above-ground part of Mentha haplocalyx, family Labiatae. Mori Folium is the dried leaves of Morus alba, family Moraceae. Chrysanthemi Flos is the dried head of Chrysanthemum morifolium, family Asteraceae. Platycodonis Radix is the dried root of Eryngium grandiflorum, family Eryngium. Glycyrrhizae Radix et Rhizoma is the dried root and rhizome of Glycyrrhiza uralensis of the Leguminosae family, and Phragmitis Rhizoma is the fresh or dried rhizome of Phragmites communis of the Gramineae family. It is recommended that the eight drugs be used in raw form as medicine. The dosage and method of decoction were converted into a modern single dosage of 7.46 g Armeniacae Semen Amarum, 5.60 g Forsythiae Fructus, 2.98 g Menthae Haplocalycis Herba, 9.33 g Mori Folium, 3.73 g Chrysanthemi Flos, 7.46 g Platycodonis Radix, 2.98 g Glycyrrhizae Radix et Rhizoma, and 11.19 g Phragmitis Rhizoma, with 400 mL water added, and the solution was boiled to obtain 200 mL, taken twice a day. Sangjuyin has the efficacy of dispersing wind and clearing heat, promoting lung and relieving cough, and it is used for treating the initial onset of wind-warmth and the evidence of evil spirits in the lungs and collaterals. Modern research has shown that Sangjuyin is often used in the treatment of cough, pneumonia, rhinitis, and other respiratory diseases, and the results of this study provide a reference for the later development of Sangjuyin.
3.Construction of an Evaluation System for Traditional Chinese Medicine Appropriate Technologies Based on Evidence-Based Medicine
Jixing WANG ; Zhiyi ZHOU ; Sisi LIN ; Dieyu MA ; Zhizhen ZHOU ; Conghua JI
Journal of Traditional Chinese Medicine 2026;67(4):355-359
Based on the theory of evidence-based medicine (EBM), this paper systematically constructed a multi-dimensional evaluation framework for traditional Chinese medicine (TCM) appropriate technologies, encompassing three core dimensions including evidence, practitioner, and patient. For the current practical challenges in the promotion of TCM technologies such as lack of high-quality evidence, inconsistent operational standards, and varying patient acceptance, the paper proposed the integration of published literature evidence and real-world research data to construct a scientific and applicable evaluation pathway. Regarding the evidence dimension, it emphasizes syste-matic assessment of effectiveness, safety, and economic efficiency, introducing methods like the target trial emulation framework to enhance evidence quality; for the practitioner dimension, it suggests developing multi-aspects competency evaluation tools based on educational background, training assessment, and clinical outcomes; for the patient dimension, it recommends designing patient acceptance assessment tools by considering factors such as technical characte-ristics, expected efficacy, patient-practitioner interaction, and the availability of alternative treatments. The purpose of the above measures is to provide methodological support for the standardized popularization and precision application of TCM appropriate technologies.
4.Ameliorating Effect of Yifei Tongluo Prescription on Bleomycin-induced Pulmonary Fibrosis in Rats via Regulating NLRP3/Caspase-1/GSDMD Signaling Pathway and Epithelial-mesenchymal Transition
Bowen ZHOU ; Zefeng LI ; Xian MA ; Xuannian LI ; Jingwen WANG ; Fei XU ; Huaman LIU ; Xinhua JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):150-159
ObjectiveTo observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin D (GSDMD) pathway and epithelial-mesenchymal transition (EMT) in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley (SD) rats were randomly divided into a blank group, a model group, a prednisone acetate group (1.17 mg·kg-1), and low- and high-dose Yifei Tongluo prescription groups (10.62 and 21.24 g·kg-1, respectively). Administration started on the 7th day after modeling, once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression of α-smooth muscle actin (α-SMA) and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome, E-cadherin (E-cad), and typeⅠ collagen (ColⅠ) in lung tissues was detected by immunofluorescence. The content of hydroxyproline (HYP), tumor necrosis factor (TNF)-α, interleukin (IL)-18, and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), IL-1β, and transforming growth factor (TGF)-β1 in rat lung tissues were determined by real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of NLRP3, GSDMD, ASC, and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group, the model group exhibited a significantly increased lung coefficient (P<0.01) and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition, the levels of α-SMA, Vimentin, E-cad, and ColⅠ in lung tissues were significantly increased (P<0.01). The levels of fibrosis- and inflammation-related factors HYP, TNF-α, IL-18, and IL-1β in serum were significantly upregulated (P<0.01). The levels of factors related to the activation of NLRP3 inflammasome in lung tissues, including NLRP3, GSDMD, ASC, Caspase-1, IL-1β, and TGF-β1, were significantly upregulated (P<0.01). Compared with the model group, the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally, the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA, Vimentin, E-cad, and ColⅠ in lung tissue was significantly decreased (P<0.01). The levels of HYP, TNF-α, IL-18, and IL-1β in serum were significantly reduced (P<0.01). The expression levels of NLRP3, GSDMD, ASC, Caspase-1, IL-1β, and TGF-β1 in lung tissue were also significantly decreased (P<0.01). ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway, down-regulate release of pro-inflammatory and pro-fibrotic cytokines, alleviate NLRP3 inflammasome-mediated pyroptosis and EMT, and thereby improve pulmonary fibrosis in rats.
5.Prediction and verification of the mechanism of Chaiqi yigan granules improving hepatocellular carcinoma
Guiping MA ; Yuanjie ZHANG ; Yichi ZHOU ; Jinzhen LYU ; Conghui WANG ; Fenping LU ; Bowen LIU ; Yun RAN ; Shiping HU
China Pharmacy 2026;37(5):620-625
OBJECTIVE To predict and validate the mechanisms of Chaiqi yigan granules (CQYG) improving hepatocellular carcinoma (HCC). METHODS The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group (normal saline), sorafenib group (positive control, 50 mg/kg), and CQYG low-, medium- and high-dose groups (24.83, 49.66, 99.32 g/kg), with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically, once a day, for 14 consecutive days. After last administration, pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition (EMT) [N-cadherin, E-cadherin, Vimentin, matrix metalloproteinase 7 (MMP7)] and the mitogen-activated protein kinase (MAPK) signaling pathway [p38 MAPK, phosphorylated p38 MAPK, c-Jun N-terminal kinase (JNK), phosphorylated JNK, extracellular regulated protein kinase 1/2 (ERK1/2), phosphorylated ERK1/2] in tumor tissue of mice. RESULTS Network pharmacology analysis revealed that metabolic pathways, pathways in cancer, and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments, the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group, CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover, the expression levels of Ki-67, N-cadherin, MMP7 and Vimentin proteins, along with the phosphorylation levels of ERK1/2 and JNK proteins, were all significantly reduced ( P <0.05). The expression level of E-cadherin protein was significantly increased ( P <0.05), the phosphorylation level of p38 MAPK protein was increased, the difference was not statistically significant ( P >0.05). CONCLUSIONS CQYG can inhibit EMT by regulating the MAPK signaling pathway, thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.
6.Mechanism of Yangjing Zhongyutang in Regulating SIRT1/PGC-1α Signaling Pathway to Promote Mitochondrial Function and Alleviate Oxidative Stress Damage in Rats with Diminished Ovarian Reserve
Ping ZHANG ; Lijuan YANG ; Shenghui CHEN ; Wenliang YAO ; Yuliang ZHOU ; Ling MA ; Huiying WU ; Yanwen XU ; Ziyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):46-55
ObjectiveTo observe the effects of Yangjing Zhongyutang (YJZYT) on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) signaling pathway in cyclophosphamide (CTX)-induced rats with diminished ovarian reserve (DOR), and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group (n=7) and a model group (n=35). Rats in the model group received a single intraperitoneal injection of CTX (90 mg·kg-1) to establish the DOR model. After modeling, estrous cycles were monitored for 7 consecutive days, and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling, rats were divided into groups for intervention: estradiol valerate group (0.09 mg·kg-1), and YJZYT high-, medium-, and low-dose groups (19.98, 9.99, 5.00 g·kg-1). The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state, body weight, and ovarian wet weight of rats were observed and recorded, and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Hematoxylin-eosin (HE) staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species (ROS) expression levels. Colorimetric assays were employed to measure adenosine triphosphate (ATP) and malondialdehyde (MDA) content in ovarian tissues. Quantitative Real-time polymerase chain reaction (Real-time PCR) was used to detect mitochondrial DNA (mtDNA) copy number and the mRNA expression levels of key genes including SIRT1, PGC-1α, nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). Western blot was performed to detect the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM. ResultsCompared with the blank group, rats in the model group exhibited disrupted estrous cycles, obviously reduced body weight, and decreased ovarian index (P<0.05). Ovarian histopathology revealed cortical thinning, loose structure, and a significant reduction in both primordial and growing follicles (P<0.01). Serum FSH and LH levels were significantly elevated (P<0.01), while E2 and AMH levels were obviously reduced (P<0.05, P<0.01). ATP content and mtDNA copy number decreased in ovarian tissue (P<0.01), ROS expression increased, MDA levels rose, while SOD and GSH-Px activities obviously decreased (P<0.05, P<0.01), mRNA and protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM were obviously downregulated (P<0.05, P<0.01). After treatment, compared with the model group, body weight and ovarian index obviously recovered in rats administered various doses of YJZYT (P<0.05), serum E2 and AMH levels increased, while FSH and LH levels obviously decreased (P<0.05, P<0.01), ovarian tissue ATP content and mtDNA copy number were up-regulated, ROS and MDA levels decreased, and antioxidant enzymes SOD and GSH-Px activity obviously increased (P<0.05, P<0.01), Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group (P<0.05, P<0.01), HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups, with a obviously increase in the number of primordial and growing follicles (P<0.05, P<0.01). Granulosa cells were neatly arranged, indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway, promoting mitochondrial biogenesis, enhancing mitochondrial function, and alleviating oxidative stress damage.
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.Comparison of sleep EEG power spectral density between depressive episode patients and schizophrenia patients with suicidal behavior
Jingwen LIU ; Yunfei ZHOU ; Jingchu HU ; Jiaoyan ZHOU ; Junwei YANG ; Jie LIANG ; Hong XU ; Yu CANG ; Shimeng MA
Sichuan Mental Health 2026;39(1):50-57
BackgroundPatients with depressive episode and schizophrenia have a high risk of suicide. The sleep electroencephalogram power spectral density characteristics of patients with depressive episode accompanied by suicidal behavior and those with schizophrenia may be different, but there is currently a lack of direct comparative studies on these two groups of patients. ObjectiveTo compare the sleep electroencephalogram power spectral density between depressive episode and schizophrenic patients with suicidal behavior, in order to provide references for exploring predictive indicators of suicidal behavior. MethodsFrom June 2018 to December 2020, 20 patients with depressive episode and 20 patients with schizophrenia who had committed suicide within the past month and were treated at the outpatient department of Shenzhen Kangning Hospital were selected. All of them met the diagnostic criteria for depressive episode or schizophrenia as defined in the International Classification of Diseases, tenth edition (ICD-10). Using a random sampling method, 20 volunteers with matching gender and age to the patient groups were selected from the Cuiping community in Shenzhen as the control group. The subjective sleep of the patients was evaluated using the Insomnia Severity Index (ISI), the Dysfunctional Belief and Attitude about Sleep (DBAS), the Disturbing Dreams and Nightmare Severity Index (DDNSI), and the Epworth Somnolence Scale (ESS). The objective sleep of the patients was assessed using polysomnography. The sleep electroencephalogram was filtered and the power spectral density of the brain wave was analyzed and processed for all the subjects. The subjective and objective sleep conditions of the two patient groups were compared, and the sleep electroencephalogram power spectral density of the patient groups and the control group were also compared. ResultsA comparison of subjective and objective sleep conditions between patients with depressive episode accompanied by suicidal behavior and patients with schizophrenia accompanied by suicidal behavior showed no statistically significant differences (P>0.05). Comparisons of sleep electroencephalogram power spectral density in the W stage (average power of α wave, total power of δ wave, average power of δ wave, average power of θ wave), N1 stage (average power of β wave, total power of α wave, total power of δ wave), N2 stage (total power of α wave, average power of α wave, total power of δ wave, average power of δ wave), N3 stage (average power of α wave, average power of δ wave), and R stage (total power of α wave, average power of α wave, total power of δ wave, average power of δ wave) between patients with depressive episode accompanied by suicidal behavior, patients with schizophrenia accompanied by suicidal behavior, and the control group showed statistically significant differences (P<0.05 or 0.01). The total power of δ wave in the W stage and the average power of β wave and δ wave in the N1 stage were higher in two patient groups were higher than those of the control group. The total power of α wave and the average power of α wave in the N2 stage were lower than those of the control group, while the average power of δ wave was higher than that of the control group. The average power of α wave in the N3 stage of both patient groups were lower than that of the control group, while the average power of δ wave was higher than that of the control group. The total power and average power of α wave in the R stage were lower than those of the control group, while the total power and average power of δ wave were higher than those of the control group. All the differences were statistically significant. Patients with depressive episode accompanied by suicidal behavior had higher average powers of α wave, δ wave, and θ wave in the W stage compared with the control group, while the total power of α wave in the N1 stage was lower in the former group. All these differences were statistically significant (P<0.05). ConclusionThe depressive episode patients accompanied by suicidal behavior have highly overlapping sleep electroencephalogram abnormal patterns with those of schizophrenia patients, mainly manifested as a general decrease in α wave power (N2, N3, R stage) and a general increase in δ wave power (W, N1, N2, N3, R stage) as well as β wave power in N1 stage. At the same time, patients with depressive episode accompanied by suicidal behavior also show specific changes, including an increase in the average power of α and θ waves during the wakefulness period (W stage), and a decrease in the total power of α wave in N1 stage. [Funded by Guangdong Province High-level Clinical Key Specialty (with supporting funds from Shenzhen City) (number, SZGSP013); Shenzhen Key Medical Discipline (number, SZXK041); Shenzhen Clinical Medicine Research Center Project (number, 20210617155253001)]
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.Clinical study on noninfectious fever of endovascular aortic repair
Zhengyue QIAN ; Yao FU ; Wenbo ZHOU ; Bingbing MA
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(02):275-280
Objective To analyze the clinical characteristics and risk factors of noninfectious fever after endovascular repair of aortic dilatation diseases, and to explore management strategies. Methods A retrospective analysis was conducted on the clinical data of patients who underwent endovascular aortic repair for aortic dilatation diseases from January 2021 to October 2023. Based on inclusion and exclusion criteria, the enrolled patients were divided into a febrile group and an afebrile group according to the presence of postoperative fever. Clinical data, including demographics and surgical details, were compared between the two groups. Multivariate logistic regression analysis was performed on indicators with P≤0.05 in the univariate analysis, and receiver operating characteristic (ROC) curves were generated to analyze the predictive value of risk factors for postoperative noninfectious fever. Results A total of 305 patients were included in the final analysis. Postoperative noninfectious fever occurred in 75.08% (229/305) of the patients, with 98.25% of cases occurring within the first two postoperative days. The febrile group (n=229) had a median age of 65.0 (IQR: 53.0, 73.0) years with 83.4% males, while the afebrile group (n=76) had a median age of 71.0 (IQR: 65.0, 76.7) years with 84.2% males. Univariate analysis showed that the age, prevalence of coronary heart disease, preoperative statin use, and prevalence of aortic aneurysm were significantly lower in the febrile group compared to the afebrile group. Logistic regression analysis indicated that age, surgical site, disease type, preoperative elevated body temperature, and stent type were significantly associated with noninfectious fever, while preoperative statin use was negatively correlated. ROC curve analysis demonstrated that age, surgical site, preoperative elevated body temperature, and stent type had significant predictive value for postoperative noninfectious fever (P<0.01). Conclusion Noninfectious fever is highly prevalent following aortic repair. The relationship between fever and infection should be comprehensively evaluated based on risk factors and changes in the patient's condition to promote the rational use of antibiotics.

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