1.Intra-articular injection of different concentrations of silicon-based bioceramics in treatment of knee osteoarthritis in rats
Jingwen GUO ; Qingwei WANG ; Zijun HE ; Zihang HU ; Zhi CHEN ; Rong ZHU ; Yuming WANG ; Wenfei LIU ; Qinglu LUO
Chinese Journal of Tissue Engineering Research 2026;30(2):288-295
BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P<0.05),and the separation of trabeculae increased(P<0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P<0.05),and the separation of trabeculae decreased(P<0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P<0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P<0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.
2.Effects of human umbilical cord blood platelet-rich plasma,mononuclear cells,and mesenchymal stem cells in repairing thin endometrium in rats
Yanli MU ; Anchun HU ; Wenchi XU ; Panpan CHEN ; Hao CHEN ; Shuyun ZHAO ; Guanyou HUANG ; Xiaojuan CHEN
Chinese Journal of Tissue Engineering Research 2026;30(1):78-92
BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95%ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P<0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P<0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P<0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P<0.001),and their expression levels decreased after treatment(all P<0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P<0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P<0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P<0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.
3.Intra-articular injection of different concentrations of silicon-based bioceramics in treatment of knee osteoarthritis in rats
Jingwen GUO ; Qingwei WANG ; Zijun HE ; Zihang HU ; Zhi CHEN ; Rong ZHU ; Yuming WANG ; Wenfei LIU ; Qinglu LUO
Chinese Journal of Tissue Engineering Research 2026;30(2):288-295
BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P<0.05),and the separation of trabeculae increased(P<0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P<0.05),and the separation of trabeculae decreased(P<0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P<0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P<0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.
4.Effects of human umbilical cord blood platelet-rich plasma,mononuclear cells,and mesenchymal stem cells in repairing thin endometrium in rats
Yanli MU ; Anchun HU ; Wenchi XU ; Panpan CHEN ; Hao CHEN ; Shuyun ZHAO ; Guanyou HUANG ; Xiaojuan CHEN
Chinese Journal of Tissue Engineering Research 2026;30(1):78-92
BACKGROUND:Research has found that human umbilical cord blood platelet rich plasma and human umbilical cord blood derived mesenchymal stem cells have certain therapeutic effects on thin endometrium.However,there are currently no reports on the study of human umbilical cord blood mononuclear cells on thin endometrium,and there is a lack of relevant research comparing the three.OBJECTIVE:To explore the effects and mechanisms of human umbilical cord blood platelet rich plasma,monocytes,and mesenchymal stem cells in repairing thin endometrium in rats.METHODS:Sixty female SPF grade SD rats were randomly divided into sham operation group,model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group,with 12 rats in each group.The sham operation group received 0.5 mL physiological saline injection into the uterine horn,followed by 0.5 mL of PBS infusion after 5 minutes;The model group,human umbilical cord blood platelet rich plasma group,human umbilical cord blood mononuclear cell group,and human umbilical cord blood derived mesenchymal stem cell group were injected with 0.5 mL of 95%ethanol by volume.After 5 minutes,the remaining ethanol was aspirated and washed twice with physiological saline.Then,0.5 mL of PBS,human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells(1×107 cells/mL),and human umbilical cord blood derived mesenchymal stem cells(1×107 cells/mL)were perfused separately.During the third normal estrus cycle after reperfusion,organs,tissues and serum were collected for testing of relevant indicators.RESULTS AND CONCLUSION:(1)The macroscopic view of uterine tissue,hematoxylin eosin staining and Masson staining results:the sham operation group had intact structure,moderate endometrial thickness,and clear vascular structure.Compared with the sham operation group,the model group showed uterine atrophy,incomplete structure,significantly reduced endometrial thickness and glandular quantity,disordered vascular structure,and increased fibrosis.Compared with the model group,after treatment with human umbilical cord blood derivatives,the size,structure,and endometrial thickness of the uterus were restored(all P<0.01),and fibrosis was reduced,with the most significant recovery observed in the human umbilical cord blood mononuclear cell group.The increase in glandular quantity was most significant in the human umbilical cord blood platelet rich plasma group(P<0.000 1).(2)The immunohistochemistry and immunofluorescence results of uterine tissue showed that compared with the sham operation group,the expression levels of cell proliferation related indicators such as keratin 9 and vimentin,endometrial receptivity related indicators such as leukemia inhibitory factor and integrin αyβ3,platelet endothelial cell adhesion molecule,basic fibroblast growth factor,and vascular endothelial growth factor were all reduced in the model group(all P<0.05).Compared with the model group,the above indicators were significantly increased after treatment with human umbilical cord blood derivatives.Comparison of human umbilical cord blood derivatives among groups showed that keratin 9 and vascular endothelial growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood platelet rich plasma group;Wave shaped protein and leukemia inhibitory factor protein:human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group;Integrin αyβ3 protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group>human umbilical cord blood mononuclear cell group;Platelet endothelial cell adhesion molecule protein:human umbilical cord blood platelet rich plasma group>human umbilical cord blood mononuclear cell group>human umbilical cord blood derived mesenchymal stem cell group;Basic fibroblast growth factor protein:human umbilical cord blood mononuclear cell group>human umbilical cord blood platelet rich plasma group>human umbilical cord blood derived mesenchymal stem cell group.(3)Western blot analysis showed that compared with the sham operation group,the protein levels of interleukin-6,interleukin-1β,and tumor necrosis factor alpha in the model group were significantly increased(all P<0.001),and their expression levels decreased after treatment(all P<0.05).(4)ELISA assay showed that compared with the sham operation group,the model group had lower levels of anti Mullerian hormone,estradiol,and progesterone,and increased levels of follicle stimulating hormone and luteinizing hormone(except for luteinizing hormone,all P<0.05).After treatment,there was a certain degree of recovery in the levels of sex hormones and anti Mullerian hormones.(5)Fertility experiments showed that compared with the sham operation group,the model group had an increase in conception time and a significant decrease in litter size(all P<0.05).After treatment with human umbilical cord blood derivatives,the litter size of all three groups increased(P<0.05),and no significant differences were found between the groups.This study preliminarily reveals that human umbilical cord blood mononuclear cells have a certain therapeutic effect on thin endometrium,and human umbilical cord blood platelet rich plasma,human umbilical cord blood mononuclear cells,and human umbilical cord blood derived mesenchymal stem cells have different advantages and differences in improving endometrial regeneration function,endometrial receptivity,angiogenesis,inflammation regulation,and improving pregnancy outcomes in thin endometrium.
5.Preparation of Trop2-ECD_HPF fusion nanoparticles and their immunotherapeutic effects against triple-negative breast cancer
HU Meilin1 ; PENG Haojie2 ; QIU Guochang2 ; MA Xiancai2 ; CHEN Xinxin1
Chinese Journal of Cancer Biotherapy 2026;33(5):494-499
[摘 要] 目的:旨在构建Trop2-ECD与幽门螺杆菌铁蛋白(HPF)融合纳米颗粒疫苗,并评价其免疫原性与抗三阴性乳腺癌(TNBC)活性。方法:构建Trop2-ECD_HPF纳米颗粒疫苗,并在293F细胞中表达和纯化。通过尺寸排阻色谱和透射电子显微镜验证疫苗的纯度和均一性。使用铝佐剂配制疫苗对雌性BALB/c小鼠进行免疫,通过酶联免疫吸附法(ELISA)检测血清中Trop2特异性抗体滴度,并评估其对4T1-Trop2肿瘤模型的抑制效果。结果:Trop2-ECD_HPF纳米颗粒粒径约20 nm,颗粒形成率较高,纯度较高,能够显著诱导小鼠产生高滴度的Trop2特异性抗体,疫苗组第6周抗体滴度达106,显著高于佐剂组(P < 0.000 1)。在动物实验中,疫苗组小鼠的肿瘤体积显著减小(抑瘤率为38.6%),肿瘤增长速度显著减缓(P < 0.001),显示出较强的抗肿瘤效果。结论:Trop2-ECD_HPF融合纳米颗粒疫苗可有效诱导特异性体液免疫应答,显著抑制TNBC生长,为靶向Trop2的纳米疫苗开发提供了实验依据。
6.Network meta-analysis of the efficacy of GLP-1 receptor agonists in the treatment of type 2 diabetes mellitus complicated with obesity/overweight
Jin ZENG ; Juliang CHEN ; Ziwei HU ; Liangran YAO ; Yakun ZHAN
China Pharmacy 2026;37(10):1357-1363
OBJECTIVE To systematically evaluate the efficacy and safety of 6 kinds of GLP-1RAs in the treatment of type 2 diabetes mellitus (T2DM) patients with overweight or obesity, and to provide evidence-based reference for clinical practice. METHODS A comprehensive search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, CNKI, VIP, Wanfang Data, and CBM from the inception to December 1, 2025. Randomized controlled trials (RCTs) were screened according to inclusion and exclusion criteria. Data extraction and risk of bias assessment were performed on the included studies. Network meta-analysis was conducted using Stata 17.0 software. RESULTS A total of 29 eligible RCTs were included, involving 7 404 patients. Six GLP-1RAs were evaluated: semaglutide, liraglutide, exenatide, dulaglutide, polyethylene glycol loxenatide, and beinaglutide. In terms of glycemic control, semaglutide had the highest probability of ranking first in reducing glycated hemoglobin (HbA1c) and fasting plasma glucose levels, followed by polyethylene glycol loxenatide. In terms of weight management, semaglutide showed the highest probability of ranking first, followed by liraglutide and exenatide. Regarding safety, dulaglutide had the highest probability of ranking first in reducing the incidence of gastrointestinal adverse events; none of the GLP-1RAs significantly increased the risk of severe hypoglycemia. Subgroup analysis revealed that liraglutide 1.8 mg, qd and exenatide extend-release 2.0 mg, qw demonstrated superior efficacy in reducing HbA1c and body weight compared with other doses/dosage forms of the same agents. CONCLUSIONS For T2DM patients with overweight or obesity, semaglutide offers the greatest benefits in glycemic control and weight reduction, while dulaglutide demonstrates superior gastrointestinal tolerability. Liraglutide 1.8 mg, qd and exenatide extend-release 2.0 mg, qw show relatively better overall efficacy in glycemic control and weight reduction among the same agents.
8.Inheritance and Current Research Status of Major Spleen-Stomach Theories in Traditional Chinese Medicine
Ling HU ; Fengyun WANG ; Xudong TANG ; Beihua ZHANG ; Yunkai DAI ; Xu CHEN ; Shiqi LI
Journal of Traditional Chinese Medicine 2026;67(1):87-94
This paper systematically reviews the core concepts and lines of theoretical inheritance of major spleen-stomach theories in traditional Chinese medicine (TCM), including spleen deficiency theory, spleen-stomach damp-heat theory, and liver-spleen disharmony theory. It is found that these theories have all undergone a developmental trajectory characterized by classical foundation, refinement of therapeutic methods, systematization of pathogenesis, and modern innovation. The evolution of spleen-stomach theory has achieved a shift from a singular focus on tonifying the spleen to regulating dynamic middle-jiao (焦) balance, and from localized spleen-stomach regulation to the circular movement of qi involving all five zang organs. In terms of modern disease-syndrome integrative research, spleen deficiency syndrome is shown to be closely associated with impairment of the gastrointestinal mucosal barrier, metabolic disorders, and gene polymorphisms related to Helicobacter pylori-associated gastric diseases. Spleen-stomach damp-heat syndrome is closely linked to hyperactive energy metabolism, inflammatory cytokines, and abnormal expression of aquaporins. Liver-spleen disharmony syndrome is mainly associated with dysregulation of the brain-gut axis and microbiota-related metabolic disorders. It is proposed that future research on spleen-stomach diseases and syndromes should further elucidate their potential multidimensional differential biological characteristics, thereby promoting the modernization of the TCM discipline of spleen-stomach studies.
9.Strategies for Building an Artificial Intelligence-Empowered Trusted Federated Evidence-Based Analysis Platform for Spleen-Stomach Diseases in Traditional Chinese Medicine
Bin WANG ; Huiying ZHUANG ; Zhitao MAN ; Lifeng REN ; Chang HE ; Chen WU ; Xulei HU ; Xiaoxiao WEN ; Chenggong XIE ; Xudong TANG
Journal of Traditional Chinese Medicine 2026;67(1):95-102
This paper outlines the development of artificial intelligence (AI) and its applications in traditional Chinese medicine (TCM) research, and elucidates the roles and advantages of large language models, knowledge graphs, and natural language processing in advancing syndrome identification, prescription generation, and mechanism exploration. Using spleen-stomach diseases as an example, it demonstrates the empowering effects of AI in classical literature mining, precise clinical syndrome differentiation, efficacy and safety prediction, and intelligent education, highlighting an upgraded research paradigm that evolves from data-driven and knowledge-driven approaches to intelligence-driven models. To address challenges related to privacy protection and regulatory compliance in cross-institutional data collaboration, a "trusted federated evidence-based analysis platform for TCM spleen-stomach diseases" is proposed, integrating blockchain-based smart contracts, federated learning, and secure multi-party computation. The deep integration of AI with privacy-preserving computing is reshaping research and clinical practice in TCM spleen-stomach diseases, providing feasible pathways and a technical framework for building a high-quality, trustworthy TCM big-data ecosystem and achieving precision syndrome differentiation.
10.Staged Characteristics of Mitochondrial Energy Metabolism in Chronic Heart Failure with Heart-Yang Deficiency Syndrome and Prescription Intervention from Theory of Reinforcing Yang
Zizheng WU ; Xing CHEN ; Lichong MENG ; Yao ZHANG ; Peng LUO ; Jiahao YE ; Kun LIAN ; Siyuan HU ; Zhixi HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):129-138
Chronic heart failure (CHF) is a complex clinical syndrome caused by ventricular dysfunction, with mitochondrial energy metabolism disorder being a critical factor in disease progression. Heart-Yang deficiency syndrome, as the core pathogenesis of CHF, persists throughout the disease course. Insufficiency of heart-Yang leads to weakened warming and propelling functions, resulting in the accumulation of phlegm-fluid, blood stasis, and dampness. This eventually causes Qi stagnation with phlegm obstruction and blood stasis with water retention, forming a vicious cycle that exacerbates disease progression. According to the theory of reinforcing Yang, the clinical experience of the traditional Chinese medicine (TCM) master Tang Zuxuan in treating CHF with heart-Yang deficiency syndrome, and achievements from molecular biological studies, this study innovatively proposes an integrated research framework of "TCM syndrome differentiation and staging-mitochondrial metabolism mechanisms-intervention with Yang-reinforcing prescriptions" which is characterized by the integration of traditional Chinese and Western medicine. Heart-Yang deficiency syndrome is classified into mild (Stage Ⅰ-Ⅱ), severe (Stage Ⅲ), and critical (Stage Ⅳ) stages. The study elucidates the precise correlations between the pathogenesis of each stage and mitochondrial metabolism disorders from theoretical, pathophysiological, and therapeutic perspectives. The mild stage is characterized by impaired biogenesis and substrate-utilization imbalance, corresponding to heart-Yang deficiency and phlegm-fluid aggregation. Linggui Zhugantang and similar prescriptions can significantly improve the expression of peroxisome proliferator-activated receptor gamma co-activator-1α(PGC-1α)/silent information regulator 2 homolog 1 (SIRT1) and ATPase activity. The severe stage centers on oxidative stress and structural damage, reflecting Yang deficiency with water overflow and phlegm-blood stasis intermingling. At this stage, Zhenwu Tang and Qiangxin Tang can effectively mitigate oxidative stress damage, increase adenosine triphosphate (ATP) content, and repair mitochondrial structure. The critical stage arises from calcium overload and mitochondrial disintegration, leading to the collapse of Yin-Yang equilibrium. At this stage, Yang-restoring and crisis-resolving prescriptions such as Fuling Sini Tang and Qili Qiangxin capsules can inhibit abnormal opening of the mitochondrial permeability transition pore (MPTP), reduce cardiomyocyte apoptosis rate, and protect mitochondrial function. By summarizing the characteristics of mitochondrial energy metabolism disorders at different stages of CHF, this study explores the application of the theory of reinforcing Yang in treating heart-Yang deficiency syndrome and provides new insights for the clinical diagnosis and treatment of CHF.

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