1.Explainable Machine Learning Model for Predicting Prognosis in Patients with Malignant Tumors Complicated by Acute Respiratory Failure: Based on the eICU Collaborative Research Database in the United States
Zihan NAN ; Linan HAN ; Suwei LI ; Ziyi ZHU ; Qinqin ZHU ; Yan DUAN ; Xiaoting WANG ; Lixia LIU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):98-108
To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework. Clinical data of patients with malignant tumors and ARF were extracted from the eICU Collaborative Research Database in the United States, including demographic characteristics, comorbidities, vital signs, laboratory test indicators, and major interventions within the first 24 hours after ICU admission.The study outcome was ICU death.Enrolled patients were randomly divided into a training set and a validation set at a ratio of 7:3.Predictor variables were selected using least absolute shrinkage and selection operator (LASSO) regression.Five machine learning algorithms-extreme gradient boosting (XGBoost), support vector machine (SVM), Logistic regression, multilayer perceptron (MLP), and C5.0 Decision Tree-were employed to construct predictive models.Model performance was evaluated based on the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and other metrics.The optimal model was further interpreted using the Shapley additive explanations (SHAP) algorithm. A total of 3196 patients with malignant tumors complicated by ARF were included.The training set comprised 2, 261 patients and the validation set 935 patients; 683 patients died during ICU stay, while 2513 survived.LASSO regression ultimately selected 12 variables closely associated with patient ICU outcomes, including sepsis comorbidity, use of vasoactive drugs, and within the first 24 hours after ICU admission: minimum mean arterial pressure, maximum heart rate, maximum respiratory rate, minimum oxygen saturation, minimum serum bicarbonate, minimum blood urea nitrogen, maximum white blood cell count, maximum mean corpuscular volume, maximum serum potassium, and maximum blood glucose.After model evaluation, the XGBoost model demonstrated the best performance.The AUCs for predicting ICU mortality risk in the training and validation sets were 0.940 and 0.763, respectively; accuracy was 88.3% and 81.2%;sensitivity was 98.5% and 95.9%.Its predictive performance also remained optimal in sensitivity analyses.SHAP analysis indicated that the top five variables contributing to the model's predictions were minimum oxygen saturation, minimum serum bicarbonate, minimum mean arterial pressure, use of vasoactive drugs, and maximum white blood cell count. This study successfully developed a mortality risk prediction model for ICU patients with malignant tumors complicated by ARF based on a large-scale dataset and performed explainability analysis.The model aids clinicians in early identification of high-risk patients and implementing individualized interventions.
2.Intervention Strategies for Heart Failure with Preserved Ejection Fraction Using Combined Classical Formulas Based on the Theory of "Disease of Both Blood and Water"
Yuzhi JIA ; Qingyong HE ; Jie WANG ; Xin ZHAO ; Ziyi WANG ; Dongmei LI ; Junqiao AN
Journal of Traditional Chinese Medicine 2026;67(4):370-374
Based on the theory of "disease of both blood and water" in Essentials from the Golden Cabinet (《金匮要略》), and in combination with the dynamic syndrome evolution of heart failure with preserved ejection fraction (HFpEF), this paper systematically clarifies the pathomechanism of HFpEF, characterized by yang deficiency as the root, blood stasis as the pivotal factor and water retention as the manifestation. Accordingly, the therapeutic principles have been proposed, which are warming yang and banking up original qi to consolidate the root, activating blood and unblocking collaterals to smooth the mechanism, and promoting urination and regulating pivot to remove the branch. On this basis, a compound formula structure of "one monarch, one minister and one assistant" is established, forming an integrated intervention strategy that synergistically combines the three methods of warming yang, activating blood, and promoting urination through combined classical formulas. Zhenwu Decoction (真武汤), which warms yang and dissolves rheum, is used to consolidate the root and directly target the source of yang deficiency, serving as the monarch; Guizhi Fuling Pills (桂枝茯苓丸), which activates blood, promotes urination and unblocks the pivot, assists in interrupting the binding of blood stasis and water retention, serving as the minister; Tingli Dazao Xiefei Decoction (葶苈大枣泻肺汤), which regulates qi, disperses retained fluids, and eliminates the manifestation, alleviates acute water-retention symptoms, serving as the assistant. This compound formula is warming without being drying, diuretic without being drastic, and dispels stasis without consuming blood, thereby achieving the therapeutic effects of warming yang, activating blood, and promoting urination.
3.Textual Research on Classical Formula Mulisan
Dongsen HU ; Xiangyang ZHANG ; Canran XIE ; Jiawei SHI ; Ziyi WANG ; Zhuoyan ZHOU ; Lin ZHANG ; Yexin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):191-200
The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas (second batch) of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha, Astragali Radix, Ephedrae Radix et Rhizoma, and wheat, with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution, composition, dosage, original plants and their processing methods, decocting method, efficacy, indications, and modern clinical application of Mulisan by tracing, comparative analysis, and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition, dosage, efficacy, and indications of Mulisan were first recorded in the Treatise on Diseases, Patterns, and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods, Ostreae Concha is the shell of Ostrea rivularis, which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica, respectively, the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum, which can be used without processing, while the stir-fried fruit, being thin and deflated, demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g, Astragali Radix 8.26 g, Ephedrae Radix et Rhizoma 8.26 g, and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL, and the decoction should be taken warm. In modern clinical practice, Mulisan has a wide range of indications, including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases, neurological diseases, respiratory system diseases, and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research, development, and clinical application of Mulisan.
4.Characterization of Animal Models of Type 2 Diabetes Mellitus with Hypertension Based on Clinical Symptoms in Traditional Chinese and Western Medicine
Ziyi WANG ; Xingyu FAN ; Yuzhi JIA ; Qingyong HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):230-236
Type 2 diabetes mellitus (T2DM) and hypertension are common and frequent chronic non-communicable diseases, which often coexist in clinical practice, resulting in a large number of cardiovascular events and deaths, and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards, guidelines, and animal model evaluation methods of T2DM with hypertension at home and abroad, this study summarized, evaluated, and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin (STZ) in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine (TCM) are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages, the ideal modeling method for T2DM with hypertension is the two-kidney, one clip (2K1C) method (a surgical induction method) combined with feeding a high-fat and high-sugar diet and STZ injection. However, the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome, which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem, it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome, which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way, ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM, which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time, breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.
5.Textual Research on Classical Formula Mulisan
Dongsen HU ; Xiangyang ZHANG ; Canran XIE ; Jiawei SHI ; Ziyi WANG ; Zhuoyan ZHOU ; Lin ZHANG ; Yexin CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):191-200
The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas (second batch) of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha, Astragali Radix, Ephedrae Radix et Rhizoma, and wheat, with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution, composition, dosage, original plants and their processing methods, decocting method, efficacy, indications, and modern clinical application of Mulisan by tracing, comparative analysis, and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition, dosage, efficacy, and indications of Mulisan were first recorded in the Treatise on Diseases, Patterns, and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods, Ostreae Concha is the shell of Ostrea rivularis, which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica, respectively, the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum, which can be used without processing, while the stir-fried fruit, being thin and deflated, demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g, Astragali Radix 8.26 g, Ephedrae Radix et Rhizoma 8.26 g, and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL, and the decoction should be taken warm. In modern clinical practice, Mulisan has a wide range of indications, including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases, neurological diseases, respiratory system diseases, and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research, development, and clinical application of Mulisan.
6.Characterization of Animal Models of Type 2 Diabetes Mellitus with Hypertension Based on Clinical Symptoms in Traditional Chinese and Western Medicine
Ziyi WANG ; Xingyu FAN ; Yuzhi JIA ; Qingyong HE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):230-236
Type 2 diabetes mellitus (T2DM) and hypertension are common and frequent chronic non-communicable diseases, which often coexist in clinical practice, resulting in a large number of cardiovascular events and deaths, and their case fatality rate far exceeds that of other factors such as dyslipidemia and obesity. Based on the diagnostic standards, guidelines, and animal model evaluation methods of T2DM with hypertension at home and abroad, this study summarized, evaluated, and analyzed the characteristics of the existing animal models of T2DM with hypertension based on the clinical symptoms in traditional Chinese and Western medicine. The animal models showing high fitting degrees with the clinical symptoms in Western medicine are mainly established by injection of streptozocin (STZ) in SHR rats in the surgical induction and chemical induction methods and feeding a high-fat and high-salt diet combined with STZ injection in SD rats in the dietary induction methods. The models showcasing high fitting degrees with the clinical symptoms in traditional Chinese medicine (TCM) are mainly established by the surgical induction method. Considering the fitting degrees and the advantages and disadvantages, the ideal modeling method for T2DM with hypertension is the two-kidney, one clip (2K1C) method (a surgical induction method) combined with feeding a high-fat and high-sugar diet and STZ injection. However, the available models lack the characteristics of TCM and the evaluation indicators have poor specificity. This study found that there are few animal models of T2DM with hypertension considering the characteristics of both disease and syndrome, which may be related to the identification and attribution of TCM syndromes in animal macroscopic information. In view of this problem, it is suggested that the evaluation criteria should be established and improved for the animal models combining disease and syndrome, which can help to evaluate the fitting degree of the pathological characteristics of different syndromes in the animal models of T2DM with hypertension. In this way, ideal animal models of T2DM with hypertension can be established to simulate the disease occurrence and development in the human body. The animal models are expected to provide an ideal approach for the further research on the pathogenesis of T2DM and its prevention and treatment with TCM, which is of great significance for the treatment and prevention of T2DM with hypertension and the prognosis of its complications. At the same time, breakthroughs in the basic syndrome models of comorbidities are expected to lay a foundation for the leapfrog development of TCM research.
7.Diagnostic and Treatment Approach to Coronary Microvascular Disease from the Perspective of "Disharmony of Blood Collaterals and Dysfunction of Qi Transformation"
Xiaoxiao ZHANG ; Jianguo LIN ; Xiaoning SUN ; Ziyi SUN ; Tong TONG ; Wenqian ZUO ; Zeqi WANG ; Kuiwu YAO
Journal of Traditional Chinese Medicine 2025;66(7):755-759
The study explores the traditional Chinese medicine (TCM) diagnostic and treatment approach to coronary microvascular disease (CMVD) from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective, different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice, four targeted treatment methods, i.e. warming, unblocking, tonifying, and activating, are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia, myocardial infarction, and coronary revascularization, with corresponding pathological mechanisms of latent pathogenic obstruction, toxic accumulation in the collaterals, and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation, staging, and transformation. Accordingly, treatment principles include warming to assist qi transformation, unblocking obstruction and dispelling turbidity, activating to disperse toxic stasis and invigorate collaterals, and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis, attention should be paid to the underlying disease, analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.
8.Association of latent profiles of mobile phone dependence and self control with physical exercise among junior high school students
YAN Chuqi, ZHANG Tiancheng, ZHANG Fulan, WANG Aolun, PENG Jinyin, CHEN Ziyi, LUO Xiangyu
Chinese Journal of School Health 2025;46(3):391-395
Objective:
To explore the association of latent profiles of mobile phone dependence and self control with physical exercise among junior high school students, so as to provide references for the prevention of mobile phone dependence and the improvement of self control among junior high school students.
Methods:
From April to May 2024, a stratified random cluster sampling method was used to select a total of 2 311 students from grade 7 to grade 9 in three public junior high schools in Xiangxi Autonomous Prefecture, Hunan Province. Latent profile analysis was conducted to identify the latent profiles of mobile phone dependence and self control among junior high school students. Pearson correlation analysis was used to examine the correlation between mobile phone dependence and self control, and Chi square test was used to analyze the distribution differences of latent profiles of adolescents across different demographic characteristics. Multiple Logistic regression analysis was applied to explore the association between mobile phone dependence, self control, and physical exercise.
Results:
Four latent profiles of mobile phone dependence and self control were identified: low dependence-moderate self control group ( n =885, 38.3%), moderate dependence-low self control group ( n =910, 39.4%), high dependence-no self control group ( n =232, 10.0%), and no dependence-high self control group ( n =284, 12.3%). Significant differences were observed in the distribution of latent profiles across gender, grade and only child status ( χ 2=10.85, 35.72, 13.85, P <0.05). Logistic regression analysis showed that, after controlling for demographic variables, compared with the low dependence-moderate self control group, physical exercise was negatively associated with the moderate dependence-low self control group ( OR =0.79) and the high dependence-no self control group ( OR =0.81), while positively associated with the no dependence-high self control group ( OR =1.58) ( P <0.01).
Conclusions
The influence of physical exercise on junior high school students different potential profile types of mobile phone dependence and self control is different. Schools and families should adopt targeted physical exercise interventions based on the characteristics of different profiles to promote the physical and mental health of junior high school students.
9.Effect of CCNA2 on Prognosis of Colon Cancer by Regulating Immune Microenvironment of Tumor Cells
Peng YANG ; Ziyi QIU ; Lingling WANG ; Yuan HU ; Zhengzhen CHEN ; Meizhen ZHONG ; Feiyue YU ; Rongyuan QIU
Cancer Research on Prevention and Treatment 2025;52(4):305-312
Objective To investigate the relationship between cyclin A2 (CCNA2) and the prognosis of colon cancer, and its possible mechanism from the perspective of immune infiltration. Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database. Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2. A total of 75 specimens of colon cancer and normal tissues were collected, and the expression level of CCNA2 was analyzed using immunohistochemical methods. Multivariate analysis was conducted to explore its relationship with clinicopathological features. Gene Set Enrichment Analysis (GSEA) was used to assess the potential molecular functions of CCNA2 in colon cancer. CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer. Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues (P<0.001). The overall survival, disease-specific survival, and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression (all P<0.05). In tumor tissues, the expression level of CCNA2 decreased with increased pathological and TNM stages (P<0.05). The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages (all P<0.001). GSEA suggested that Wnt/β-catenin, KRAS, and other signaling pathways were enriched when CCNA2 was lowly expressed. CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low. Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage. It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways, thereby reducing immune-cell infiltration and promoting colon cancer progression, leading to poor prognosis.
10.Study on the safety and pharmacological effect on improving dyspepsia of Shuangshu decoction in rats
Xinyuan CHEN ; Changzhou XIONG ; Jiongfen LI ; Kangyi YU ; Huan XU ; Yingxia WANG ; Dan LIAO ; Junyu TAO ; Ziyi YANG ; Caizhi LIN
China Pharmacy 2025;36(9):1059-1064
OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia (FD) in rats. METHODS In safety test, 40 rats were divided into blank control group, Shuangshu decoction low-dose, medium- dose and high-dose groups [108, 216, 324 g/(kg·d), calculated by raw medicine, the same applies below]; they were given relevant medicine intragastrically, for continuous 14 days. The mortality and toxic reactions of rats were recorded, and the organ indexes of the liver, kidney, spleen, lung and heart of rats were calculated; the pathological morphological changes in the liver, kidney, spleen, lung, heart, stomach, duodenum, and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded, and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed, and blood routine and serum biochemical indicators were measured, in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group, model group, and Shuangshu decoction low-, medium-, and high-dose groups (9.45, 18.9, 37.8 g/kg), with 10 rats in each group. Except for blank control group, rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide (3.5 mg/kg). Rats in each group were administered the corresponding drug solution/normal saline intragastrically, once a day, for 14 consecutive days. After the last medication, fecal moisture content, intestinal propulsion rate, gastric emptying rate and serum level of motilin were all detected, and interstitial cell of Cajal (ICC) ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group, and no significant difference was found in organ coefficient, routine blood and serum biological index, compared to blank control group (P>0.05); no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that, compared with the blank control group, the fecal moisture content, gastric emptying rate, intestinal propulsion rate, and serum motilin levels in the model group were significantly decreased (P<0.05); in the colonic tissue, the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae, and the endoplasmic reticulum was dilated. Compared with model group, the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators (P< 0.05); additionally, there was a large number of mitochondria in the ICC of the colonic tissue, with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats; its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion, as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.


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