1.Application and Prospect of State-target Pattern Differentiation and Treatment Theory in Signaling Pathways of Chronic Obstructive Pulmonary Disease
Xiaofang HE ; Xiaoli XIA ; Yanping MA ; Yafeng WANG ; Wenxia RAN ; Huijing XIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):254-261
The prevention and treatment of chronic obstructive pulmonary disease (COPD) pose a major global challenge, with difficulties in effectively integrating holistic regulation and precise micro-intervention. The traditional Chinese medicine (TCM) theory of state-target pattern differentiation and treatment advocates the combination of state regulation and target intervention, offering a new paradigm for integrated TCM and Western medicine. This article systematically reviews the theoretical connotations of this theory and constructs a dynamic correspondence framework linking TCM pattern states, signaling pathways, and targeted interventions across different stages of COPD. At the acute exacerbation stage, the phlegm-heat obstructing the lung state is characterized by hyperactivation of the nuclear factor (NF)-κB/NOD-like receptor protein 3 (NLRP3) inflammation pathway, and formulas for clearing heat and resolving phlegm suppress the cytokine storm through multi-component synergy. At the stable stage, the lung-spleen Qi deficiency state is characterized by functional decompensation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) antioxidative stress pathway, and therapies for tonifying the lung and spleen repair the essence of Qi deficiency through antioxidative defense and energy metabolism. At the severe/very severe stable stage, the lung-kidney deficiency state is pathologically based on dysregulation of the transforming growth factor (TGF)-β/Wnt repair network and depletion of stem/progenitor cells, and therapies for tonifying the kidney and reinforcing Qi absorption achieve simultaneous regulation of deficiency and stasis by inhibiting aberrant fibrosis and guiding ordered regeneration. These three pathways are not isolated but exhibit dynamic shifts in dominance and cross-talk, constituting the molecular network basis of deficiency causing excess and intermingled deficiency and excess. Furthermore, this article points out the current shortcomings in quantitative evidence, objective syndrome standardization, and coverage of syndrome states, and proposes future directions including building multi-omics databases, conducting biomarker-stratified randomized controlled trials, and developing disease-pattern combined animal models, aiming to provide a theoretical perspective that integrates holism and micro-targeting for precision prevention and treatment of COPD.
2.Application and Prospect of State-target Pattern Differentiation and Treatment Theory in Signaling Pathways of Chronic Obstructive Pulmonary Disease
Xiaofang HE ; Xiaoli XIA ; Yanping MA ; Yafeng WANG ; Wenxia RAN ; Huijing XIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):254-261
The prevention and treatment of chronic obstructive pulmonary disease (COPD) pose a major global challenge, with difficulties in effectively integrating holistic regulation and precise micro-intervention. The traditional Chinese medicine (TCM) theory of state-target pattern differentiation and treatment advocates the combination of state regulation and target intervention, offering a new paradigm for integrated TCM and Western medicine. This article systematically reviews the theoretical connotations of this theory and constructs a dynamic correspondence framework linking TCM pattern states, signaling pathways, and targeted interventions across different stages of COPD. At the acute exacerbation stage, the phlegm-heat obstructing the lung state is characterized by hyperactivation of the nuclear factor (NF)-κB/NOD-like receptor protein 3 (NLRP3) inflammation pathway, and formulas for clearing heat and resolving phlegm suppress the cytokine storm through multi-component synergy. At the stable stage, the lung-spleen Qi deficiency state is characterized by functional decompensation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) antioxidative stress pathway, and therapies for tonifying the lung and spleen repair the essence of Qi deficiency through antioxidative defense and energy metabolism. At the severe/very severe stable stage, the lung-kidney deficiency state is pathologically based on dysregulation of the transforming growth factor (TGF)-β/Wnt repair network and depletion of stem/progenitor cells, and therapies for tonifying the kidney and reinforcing Qi absorption achieve simultaneous regulation of deficiency and stasis by inhibiting aberrant fibrosis and guiding ordered regeneration. These three pathways are not isolated but exhibit dynamic shifts in dominance and cross-talk, constituting the molecular network basis of deficiency causing excess and intermingled deficiency and excess. Furthermore, this article points out the current shortcomings in quantitative evidence, objective syndrome standardization, and coverage of syndrome states, and proposes future directions including building multi-omics databases, conducting biomarker-stratified randomized controlled trials, and developing disease-pattern combined animal models, aiming to provide a theoretical perspective that integrates holism and micro-targeting for precision prevention and treatment of COPD.
3.Evaluation of Right Ventricular Function in Cardiac Amyloidosis by Two-Dimensional Speckle Tracking Imaging
Huiying CHEN ; Xiaojing MA ; Juan XIA ; Yafeng HE ; Jingjing WANG ; Jinlong ZHONG
Chinese Journal of Medical Imaging 2025;33(6):638-644
Purpose To investigate the value of two-dimensional speckle tracking in evaluating right ventricular function in cardiac amyloidosis(CA).Materials and Methods A total of 25 patients with CA,30 patients with hypertrophic cardiomyopathy(HCM)and 30 healthy controls were retrospectively selected from July 2021 to October 2023 in Wuhan Asia Heart Hospital.The regional difference was represented by the formula apical ratio.The parameters of conventional echocardiography,two-dimensional strain and apical ratio of the three groups were analyzed and compared.Results Only segmental strain was different in right ventricular structure and function between CA group and HCM group,and the differences were statistically significant(all P<0.05).In the CA group,the strain gradient of the right ventricle from the apex of the heart to the base was the same as that of the left ventricle,that was,the"apex preservation"pattern,which was not seen in the HCM group and the control group.Comparison of the right ventricular free wall longitudinal strain-apical ratio,right ventricle four-chamber longitudinal strain-apical ratio,left ventride global longitudinal strain-apical ratio among the three groups,it was found that the levels of CA group were higher than HCM group and control group,and the differences were statistically significant(H=40.40,43.18,55.43,all P<0.05).The right ventricular free wall longitudinal strain-apical ratio had the highest CA recognition value,the area under the curve was 0.935,sensitivity was 96%and specificity was 83%.Conclusion Two-dimensional speckle tracking can accurately evaluate the right ventricular function impairment in CA patients and provide a new choice for clinical evaluation and identification of CA patients.
4.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
5.Radiomics models based on fluid attenuated inversion recovery and contrast enhanced MRI for noninvasive prediction of isocitrate dehydrogenase mutation status in glioma
Qian'ang MA ; Jun LU ; Qi YAO ; Yafeng DONG ; Xuejun CHEN ; Jinrong QU
Journal of Practical Radiology 2025;41(6):915-919
Objective To investigate the value of MRI radiomics for the preoperative noninvasive prediction of isocitrate dehydrogenase(IDH)mutation status in glioma.Methods Totally,306 glioma patients were retrospectively selected.All patients were randomly assigned into training group(n=214)and validation group(n=92)at a ratio of 7∶3.Region of interest(ROI)was manually delineated by two radiologists independently on the fluid attenuated inversion recovery(FLAIR)and contrast enhanced(CE)MRI images for obtaining whole volume of interest(VOI)of lesion.A total of 851 radiomics features were extracted from the VOI,respectively.The least absolute shrinkage and selection operator(LASSO)method was used for features dimension reduction combing 10-fold cross validation.Three Radiomics score(Radscore)were calculated by linear combination of retained features and their corresponding coefficients.The optimal Radscore and clinical characteristics were incorporated to perform logistic regression analysis for establishing the IDH mutation status noninvasive prediction model.A nomogram was plotted for realizing the visualization of model.The receiver operating characteristic(ROC)curve was plotted to evaluate the prediction performance of model.The calibration and clinical utility of the model were evaluated by calibration curve and decision curve.Results The area under the curve(AUC)of Radscore-combined based on combination of two sequences was 0.856 in the training group,which was superior to the Radscore-CE(AUC=0.821),Radscore-FLAIR(AUC=0.766)from single sequence,with consistent result in the validation group.The addition of clinical characteristics to the model improved predictive value with AUC,sensitivity and specificity of 0.898,79.59%,90.52%in the training group.Conclusion The radiomics model based on FLAIR and CE MRI contributes to preoperative noninvasive prediction of IDH mutation status in glioma.The combination of multi-sequence and the addition of clinical characteristics can improve the prediction performance.
6.Radiomics models based on fluid attenuated inversion recovery and contrast enhanced MRI for noninvasive prediction of isocitrate dehydrogenase mutation status in glioma
Qian'ang MA ; Jun LU ; Qi YAO ; Yafeng DONG ; Xuejun CHEN ; Jinrong QU
Journal of Practical Radiology 2025;41(6):915-919
Objective To investigate the value of MRI radiomics for the preoperative noninvasive prediction of isocitrate dehydrogenase(IDH)mutation status in glioma.Methods Totally,306 glioma patients were retrospectively selected.All patients were randomly assigned into training group(n=214)and validation group(n=92)at a ratio of 7∶3.Region of interest(ROI)was manually delineated by two radiologists independently on the fluid attenuated inversion recovery(FLAIR)and contrast enhanced(CE)MRI images for obtaining whole volume of interest(VOI)of lesion.A total of 851 radiomics features were extracted from the VOI,respectively.The least absolute shrinkage and selection operator(LASSO)method was used for features dimension reduction combing 10-fold cross validation.Three Radiomics score(Radscore)were calculated by linear combination of retained features and their corresponding coefficients.The optimal Radscore and clinical characteristics were incorporated to perform logistic regression analysis for establishing the IDH mutation status noninvasive prediction model.A nomogram was plotted for realizing the visualization of model.The receiver operating characteristic(ROC)curve was plotted to evaluate the prediction performance of model.The calibration and clinical utility of the model were evaluated by calibration curve and decision curve.Results The area under the curve(AUC)of Radscore-combined based on combination of two sequences was 0.856 in the training group,which was superior to the Radscore-CE(AUC=0.821),Radscore-FLAIR(AUC=0.766)from single sequence,with consistent result in the validation group.The addition of clinical characteristics to the model improved predictive value with AUC,sensitivity and specificity of 0.898,79.59%,90.52%in the training group.Conclusion The radiomics model based on FLAIR and CE MRI contributes to preoperative noninvasive prediction of IDH mutation status in glioma.The combination of multi-sequence and the addition of clinical characteristics can improve the prediction performance.
7.Evaluation of Right Ventricular Function in Cardiac Amyloidosis by Two-Dimensional Speckle Tracking Imaging
Huiying CHEN ; Xiaojing MA ; Juan XIA ; Yafeng HE ; Jingjing WANG ; Jinlong ZHONG
Chinese Journal of Medical Imaging 2025;33(6):638-644
Purpose To investigate the value of two-dimensional speckle tracking in evaluating right ventricular function in cardiac amyloidosis(CA).Materials and Methods A total of 25 patients with CA,30 patients with hypertrophic cardiomyopathy(HCM)and 30 healthy controls were retrospectively selected from July 2021 to October 2023 in Wuhan Asia Heart Hospital.The regional difference was represented by the formula apical ratio.The parameters of conventional echocardiography,two-dimensional strain and apical ratio of the three groups were analyzed and compared.Results Only segmental strain was different in right ventricular structure and function between CA group and HCM group,and the differences were statistically significant(all P<0.05).In the CA group,the strain gradient of the right ventricle from the apex of the heart to the base was the same as that of the left ventricle,that was,the"apex preservation"pattern,which was not seen in the HCM group and the control group.Comparison of the right ventricular free wall longitudinal strain-apical ratio,right ventricle four-chamber longitudinal strain-apical ratio,left ventride global longitudinal strain-apical ratio among the three groups,it was found that the levels of CA group were higher than HCM group and control group,and the differences were statistically significant(H=40.40,43.18,55.43,all P<0.05).The right ventricular free wall longitudinal strain-apical ratio had the highest CA recognition value,the area under the curve was 0.935,sensitivity was 96%and specificity was 83%.Conclusion Two-dimensional speckle tracking can accurately evaluate the right ventricular function impairment in CA patients and provide a new choice for clinical evaluation and identification of CA patients.
8.Research on Construction of Index System for the Quality Evaluation of Multidisciplinary Diagnosis and Treatment Model for Cancer on the Multi Case Coding
Yiqing MAO ; Wenjie MA ; Bowen ZHANG ; Xinrui YANG ; Shuwan CHEN ; Yafeng ZHANG ; Mengyu YANG ; Shanshan YANG ; Chengzeng WANG
Chinese Hospital Management 2024;44(7):36-41
Objective It aims to construct a quality evaluation index system for cancer multidisciplinary diagnosis and treatment(MDT)model in China from a full process perspective,providing guidance for practical application and model optimization.Methods Based on the number of MDT publications and practical situations,20 provincial-level hospitals nationwide were selected as typical cases.Rooted theory was used to extract evaluation indicators from the original text of the cases through three-level coding.A cancer MDT quality evaluation index system was constructed under the Input-Process-Output framework.Results Through three-level coding,27 initial categories,8 subcategories,and 3 main categories were sorted out,and a cancer MDT quality evaluation index system was constructed with input,process,and output as the primary evaluation indicators,and top-level design,management system,object resources,meeting preparation,meeting progress,plan implementation,patient outcomes,and hospital outcomes as the secondary evaluation indicators.Conclusion The quality evaluation index system of cancer MDT mode based on the perspective of the entire process can effectively guide practical optimization,but there is still a need for the improvement of supporting policies and information systems to assist in quality evaluation.
9.Predictive value of inflammatory cells and clinical features in prognosis for non-small cell lung cancer immunotherapy
Qingyue ZHENG ; Chunliang YAN ; Qishan XUE ; Yafeng LIU ; Liyun MA ; Xiyan REN
Chongqing Medicine 2024;53(16):2496-2502
Objective To investigate the predictive value of inflammatory cells and clinical features in the prognosis of immune checkpoint inhibitors (ICIs) treating non-small cell lung cancer (NSCLC).Methods The data of 163 cases of stage Ⅲ and Ⅳ NSCLC patients treated with the ICIs in this hospital from January 1,2017 to December 31,2022 were collected.The CT examination was conducted after 6-8 weeks treatment.The pa-tients were divided into the objective remission group[complete remission (CR)+partial remission (PR)]and non-objective remission group[stable disease (SD)+progressed disease (PD)],disease control group (CR+PR+SD) and non-disease control group (PD),persistent clinical benefit group (DCB) and non-DCB group.The differences in clinical features and inflammatory cells indicators were compared among the differ-ent groups.The receiver operating characteristic (ROC) curve was adopted to evaluate the predictive efficiency of the inflammatory cells indicators for DCB.The influencing factors analysis of progression free survival (PFS) time and overall survival (OS) time adopted the Cox regression analysis.Results The lymphocyte count (ALC) in the disease control group was higher than that in the non-disease control group.The neutro-phil to lymphocyte ratio (NLR),platelet-lymphocyte ratio (PLR) and mononuclear lymphocyte ratio (MLR) were lower than those in the non-disease control group.The proportions of squamous cell carcinoma,stage Ⅲ,ECOG score 0-1 point,adverse reactions in the DCB group were higher than those in the non-DCB group (P<0.05),the PLT count,NLR,PLR and MLR were lower than those in the non-DCB group (P<0.05). The ROC curve analysis results showed that PLT,NLR,PLR and MLR could serve as the indicators for pre-dicting DCB,the area under of ROC curve (AUC) was 0.633,0.602,0.635 and 0.604 respectively,the opti-mal cut off values were 187×109/L (P=0.004),5.0 (P=0.026),235 (P=0.003) and 0.35 (P=0.024) re-spectively.The multivariate Cox regression analysis showed that non-squamous carcinoma including adenocar-cinoma (HR=1.565,95%CI:1.057-2.316) and other pathologic types (HR=2.285,95%CI:1.326-3.936),ECOG score 2-3 points (HR=2.375,95%CI:1.652-3.415),AMC≥0.65×109/L (HR=1.847,95%CI:1.160-2.938) and PLR≥235 (HR=1.557,95%CI:1.016-2.386) were the independent risk factors for short PFS.The ECOG score 2-3 points (HR=4.615,95%CI:2.882-7.391),AMC≥0.65×109/L (HR=5.161,95%CI:2.984-8.925) and PLR ≥235 (HR=1.732,95%CI:1.059-2.833) were the independent risk fac-tors for short OS (P<0.05),and having adverse reactions (HR=0.472,95%CI:0.294-0.757) was the independ-ent protective factor for short OS (P<0.05).Conclusion Lower PLT,AMC,NLR,MLR and PLR,higher ALC,squamous cell carcinoma,TNM stage Ⅲ,ECOG score 0-1 point and immunotherapy related adverse reactions could prompt that the prognosis is good in ICIs treating advanced NSCLC.PLT,NLR,PLR and MLR could serve as the indicators for predicting DCB.
10.A recombinant adeno-associated virus expressing secretory TGF-β type Ⅱ receptor inhibits triple-negative murine breast cancer 4T1 cell proliferation and lung metastasis in mice
Zhi CUI ; Cuijiao MA ; Qianru WANG ; Jinhao CHEN ; Ziyang YAN ; Jianlin YANG ; Yafeng LÜ ; Chunyu CAO
Journal of Southern Medical University 2024;44(5):818-826
Objective To investigate the effects of an adeno-associated virus(AAV2)vector expressing secretory transforming growth factor-β(TGF-β)type Ⅱ receptor(sTβRⅡ)extracellular domain-IgG2a Fc fusion protein(sTβRⅡ-Fc)on proliferation and migration of triple-negative murine breast cancer 4T1 cells in mice.Methods The pAAV-sTβRⅡ-Fc vector expressing sTβRⅡ-Fc fusion protein constructed by molecular cloning,the capsid protein-expressing vector pAAV2 and the helper vector were co-transfected into HEK 293T cells to prepare the recombinant AAV2-sTβRⅡ virus,which was purified by density gradient centrifugation with iodixanol.Western blotting was used to examine the effects of AAV-sTβRⅡ virus on Smad2/3 phosphorylation in 4T1 cells and on expression levels of E-cadherin,vimentin and p-Smad2/3 in 4T1 cell xenografts in mice.BALB/c mice bearing subcutaneous xenografts of luciferase-expressing 4T1 cells received intravenous injections of AAV-sTβRⅡ virus,AAV-GFP virus or PBS(n=6)through the tail vein,and the proliferation and migration of 4T1 cells were analyzed with in vivo imaging.Ki67 expression in the tumor tissues and sTβRⅡ protein expressions in mouse livers were detected with immunohistochemistry and immunofluorescence staining,and tumor metastases in the vital organs were examined with HE staining.Results The recombinant pAAV-sTβRⅡ-Fc vector successfully expressed sTβRⅡ in HEK 293T cells.Infection with AAV2-sTβRⅡ virus significantly reduced TGF-β1-induced Smad2/3 phosphorylation in 4T1 cells and effectively inhibited proliferation and lung metastasis of 4T1 xenografts in mice(P<0.05).In the tumor-bearing mice,intravenous injection of AAV-sTβRⅡ virus significantly increased E-cadherin expression,reduced vimentin and Ki67 protein expressions and Smad2/3 phosphorylation level in the tumor tissues(P<0.05 or 0.01),and induced liver-specific sTβRⅡ expression without causing body weight loss or heart,liver,spleen or kidney pathologies.Conclusion The recombinant AVV2 vector encoding sTβRⅡ extracellular domain is capable of blocking the TGF-β signaling pathway to inhibit the proliferation and lung metastasis of 4T1 cells in mice.

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