1.Mechanisms of Intervertebral Disc Degeneration and Traditional Chinese Medicine Intervention Based on Inflammatory-related Signaling Pathways
Long YANG ; Chen-Chen WANG ; Tao HUANG ; Xin-Feng LIU ; Lin-Lin HE ; Tian-Long ZHANG ; Yan-Jun ZHANG
Progress in Biochemistry and Biophysics 2026;53(5):1115-1131
Intervertebral disc degeneration (IVDD) is the predominant pathological contributor to chronic low back pain, a pervasive musculoskeletal condition affecting over 630 million people globally and imposing tremendous socioeconomic and public health burdens. The etiopathogenesis of IVDD is remarkably complex and multifactorial, involving intricate crosstalk among chronic inflammatory responses, extracellular matrix (ECM) catabolism, cellular senescence, aberrant programmed cell death (including apoptosis, pyroptosis, and ferroptosis), mitochondrial dysfunction, and oxidative damage. Compelling evidence indicates that the inflammatory microenvironment acts as a decisive driving force throughout the entire degenerative course of IVDD. Among the diverse inflammatory mediators, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serve as core pro-inflammatory cytokines that initiate and perpetuate the degenerative cascade. These two pivotal cytokines collectively activate an array of canonical intracellular signaling pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascade. Such interconnected signaling networks trigger a self-reinforcing positive feedback loop, which exacerbates inflammatory reactions, disrupts the anabolic-catabolic homeostasis of the ECM, promotes oxidative stress and mitochondrial injury, induces multiple forms of disc cell death, and ultimately leads to progressive structural collapse and functional deterioration of the intervertebral disc. Conventional therapeutic strategies, dominated by nonsteroidal anti-inflammatory drugs and surgical interventions, are limited by systemic adverse reactions, suboptimal long-term efficacy, and the risk of adjacent segment degeneration. In contrast, traditional Chinese medicine (TCM) exhibits prominent advantages in the prevention and treatment of IVDD by virtue of its holistic regulation, syndrome differentiation, and multi-component, multi-target, multi-pathway pharmacological properties. This review systematically elucidates the molecular mechanisms by which inflammation-associated signaling pathways modulate disc cell fate and ECM metabolic homeostasis, and comprehensively summarizes the experimental progress over the past five years on TCM monomers and compound formulas for intervening in IVDD. Accumulating studies have confirmed that numerous natural active ingredients isolated from herbal medicines (ferulic acid, mangiferin, paeonol, astragaloside IV) and representative TCM compound prescriptions (Bushen Huoxue Formula, Shensuitongzhi Formula, Fuzi Decoction) exert synergistic protective effects by coordinately targeting core signaling hubs. These TCM agents demonstrate potent anti-inflammatory, antioxidant, anti-apoptotic, anti-pyroptotic, anti-ferroptotic, ECM-protective, and autophagy-regulating bioactivities, thereby effectively decelerating the pathological progression of IVDD. Despite remarkable progress, current investigations are still confronted by several critical limitations. Most studies are restricted to validating the regulatory effects of single TCM components on individual signaling pathways, leaving the systematic, dynamic, and synergistic mechanisms of TCM compound formulas within multi-pathway regulatory networks largely unexplored. Furthermore, clinical translation of TCM is severely hampered by the lack of efficient targeted drug delivery systems, unclear pharmacokinetic profiles, suboptimal local bioavailability, and incomplete long-term safety assessments. Therefore, future research should adopt an interdisciplinary paradigm integrating multi-omics technologies, artificial intelligence, organoid models, and organ-on-chip systems to systematically decipher the scientific basis of TCM against IVDD. Concurrently, the development of intelligent, site-specific delivery systems (hydrogels, nanoparticles, exosome-based carriers) is urgently needed to enhance the local accumulation and sustained release of TCM ingredients. By deepening mechanistic exploration and accelerating translational research, TCM is expected to evolve into safe, effective, and personalized precision therapeutic regimens for IVDD, offering novel and reliable solutions for the clinical management of chronic low back pain.
2.Mechanisms of Intervertebral Disc Degeneration and Traditional Chinese Medicine Intervention Based on Inflammatory-related Signaling Pathways
Long YANG ; Chen-Chen WANG ; Tao HUANG ; Xin-Feng LIU ; Lin-Lin HE ; Tian-Long ZHANG ; Yan-Jun ZHANG
Progress in Biochemistry and Biophysics 2026;53(5):1115-1131
Intervertebral disc degeneration (IVDD) is the predominant pathological contributor to chronic low back pain, a pervasive musculoskeletal condition affecting over 630 million people globally and imposing tremendous socioeconomic and public health burdens. The etiopathogenesis of IVDD is remarkably complex and multifactorial, involving intricate crosstalk among chronic inflammatory responses, extracellular matrix (ECM) catabolism, cellular senescence, aberrant programmed cell death (including apoptosis, pyroptosis, and ferroptosis), mitochondrial dysfunction, and oxidative damage. Compelling evidence indicates that the inflammatory microenvironment acts as a decisive driving force throughout the entire degenerative course of IVDD. Among the diverse inflammatory mediators, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) serve as core pro-inflammatory cytokines that initiate and perpetuate the degenerative cascade. These two pivotal cytokines collectively activate an array of canonical intracellular signaling pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) cascade. Such interconnected signaling networks trigger a self-reinforcing positive feedback loop, which exacerbates inflammatory reactions, disrupts the anabolic-catabolic homeostasis of the ECM, promotes oxidative stress and mitochondrial injury, induces multiple forms of disc cell death, and ultimately leads to progressive structural collapse and functional deterioration of the intervertebral disc. Conventional therapeutic strategies, dominated by nonsteroidal anti-inflammatory drugs and surgical interventions, are limited by systemic adverse reactions, suboptimal long-term efficacy, and the risk of adjacent segment degeneration. In contrast, traditional Chinese medicine (TCM) exhibits prominent advantages in the prevention and treatment of IVDD by virtue of its holistic regulation, syndrome differentiation, and multi-component, multi-target, multi-pathway pharmacological properties. This review systematically elucidates the molecular mechanisms by which inflammation-associated signaling pathways modulate disc cell fate and ECM metabolic homeostasis, and comprehensively summarizes the experimental progress over the past five years on TCM monomers and compound formulas for intervening in IVDD. Accumulating studies have confirmed that numerous natural active ingredients isolated from herbal medicines (ferulic acid, mangiferin, paeonol, astragaloside IV) and representative TCM compound prescriptions (Bushen Huoxue Formula, Shensuitongzhi Formula, Fuzi Decoction) exert synergistic protective effects by coordinately targeting core signaling hubs. These TCM agents demonstrate potent anti-inflammatory, antioxidant, anti-apoptotic, anti-pyroptotic, anti-ferroptotic, ECM-protective, and autophagy-regulating bioactivities, thereby effectively decelerating the pathological progression of IVDD. Despite remarkable progress, current investigations are still confronted by several critical limitations. Most studies are restricted to validating the regulatory effects of single TCM components on individual signaling pathways, leaving the systematic, dynamic, and synergistic mechanisms of TCM compound formulas within multi-pathway regulatory networks largely unexplored. Furthermore, clinical translation of TCM is severely hampered by the lack of efficient targeted drug delivery systems, unclear pharmacokinetic profiles, suboptimal local bioavailability, and incomplete long-term safety assessments. Therefore, future research should adopt an interdisciplinary paradigm integrating multi-omics technologies, artificial intelligence, organoid models, and organ-on-chip systems to systematically decipher the scientific basis of TCM against IVDD. Concurrently, the development of intelligent, site-specific delivery systems (hydrogels, nanoparticles, exosome-based carriers) is urgently needed to enhance the local accumulation and sustained release of TCM ingredients. By deepening mechanistic exploration and accelerating translational research, TCM is expected to evolve into safe, effective, and personalized precision therapeutic regimens for IVDD, offering novel and reliable solutions for the clinical management of chronic low back pain.
3.Mechanism of Gushining Granules in Attenuating Dexamethasone-induced Apoptosis of Bone Marrow Mesenchymal Stem Cells via Activating PI3K/Akt/Bad Signalling Pathway
Chengyu CHU ; Lei ZHU ; Long LIANG ; Feng WANG ; Xuejian YU ; Wenwu LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):115-122
ObjectiveTo establish steroid-induced osteonecrosis of the femoral head (SANFH) cell model by using dexamethasone (DEX)-induced bone marrow mesenchymal stem cells (BMSCs) and demonstrate that Gushing Granules (GSNs) exert an improving effect by activating the phosphatidylinositol-3-kinase/protein kinase B/B-lymphoma-2 gene related promoter (PI3K/Akt/Bad) signalling pathway. MethodsFirstly, SD rats were orally administered with drugs at a dose of 0.9 g·kg-1 to prepare GSN-containing serum, and CCK-8 screening was used to determine the optimal dosage and duration of action. Then, BMSCs were cultured and treated with 1×10-6 mol·L-1 DEX, 10% GSN-containing serum, and inhibitor LY294002 of PI3K/Akt signalling pathway for 24 hours to model and group SANFH cells. Cell viability and proliferation were detected by using CCK-8 assay kit and EdU staining kit. Flow cytometry was used to detect cell apoptosis. An alkaline phosphatase (ALP) assay kit was employed to detect ALP expression. In order to detect the PI3K/Akt/Bad signalling pathway and protein and mRNA expression of apoptosis-related proteins such as apoptosis regulatory factors B-cell lymphoma-2 gene (Bcl-2), and Bcl-2-associated X protein (Bax), osteocalcin (OCN), and Collagen Ⅰ, we used Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsThe CCK-8 assay kit determined that the optimal dosage for GSN-containing serum is 10%, and the duration of action is 48 hours. After modelling and grouping the cells in each group, the detection results showed that the SANFH model group had significantly lower cell viability, cell proliferation, and ALP expression, as well as protein and mRNA expressions of PI3K, Akt, Bad, Bcl-2, OCN, and Collagen I compared to the blank group. The nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly increased (P<0.05,P<0.01). After treatment with GSN-containing serum, cell viability, cell proliferation, and ALP expression, as well as expressions of PI3K, Akt, Bad, Bcl-2, OCN, and Collagen Ⅰ nucleic acids and proteins were significantly increased, while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly decreased(P<0.05,P<0.01). Compared with the GSN drug-containing serum group, the simultaneous treatment with the inhibitor LY294002 and GSN drug-containing serum reversed the improvement effect of GSN. Specifically, the cell viability, cell proliferation, ALP expression, and the nucleic acid and protein levels of PI3K, Akt, Bad, Bcl-2, OCN, and Collagen Ⅰ were all significantly decreased, while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry were significantly increased (P<0.05, P<0.01). ConclusionGSNs antagonize DEX-induced apoptosis of BMSCs by activating the PI3K/Akt/Bad signalling pathway, providing a scientific theoretical basis for the clinical treatment of SANFH with GSNs.
4.Status of Clinical Practice Guideline Information Platforms
Xueqin ZHANG ; Yun ZHAO ; Jie LIU ; Long GE ; Ying XING ; Simeng REN ; Yifei WANG ; Wenzheng ZHANG ; Di ZHANG ; Shihua WANG ; Yao SUN ; Min WU ; Lin FENG ; Tiancai WEN
Medical Journal of Peking Union Medical College Hospital 2025;16(2):462-471
Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.
5.Heterogeneity of Adipose Tissue From a Single-cell Transcriptomics Perspective
Yong-Lang WANG ; Si-Si CHEN ; Qi-Long LI ; Yu GONG ; Xin-Yue DUAN ; Ye-Hui DUAN ; Qiu-Ping GUO ; Feng-Na LI
Progress in Biochemistry and Biophysics 2025;52(4):820-835
Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.
6.Terms Related to The Study of Biomacromolecular Condensates
Ke RUAN ; Xiao-Feng FANG ; Dan LI ; Pi-Long LI ; Yi LIN ; Zheng WANG ; Yun-Yu SHI ; Ming-Jie ZHANG ; Hong ZHANG ; Cong LIU
Progress in Biochemistry and Biophysics 2025;52(4):1027-1035
Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.
7.Research on BP Neural Network Method for Identifying Cell Suspension Concentration Based on GHz Electrochemical Impedance Spectroscopy
An ZHANG ; A-Long TAO ; Qi-Hang RAN ; Xia-Yi LIU ; Zhi-Long WANG ; Bo SUN ; Jia-Feng YAO ; Tong ZHAO
Progress in Biochemistry and Biophysics 2025;52(5):1302-1312
ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.
8.Retrospective Clinical Analysis on Lead Extraction and Reimplantation Strategies,Success and Complication Rates During Upgrade of Cardiovascular Implantable Electronic Devices in Non-infected Patients
Cuizhen YUAN ; Feng ZE ; Ding LI ; Jiangbo DUAN ; Xu ZHOU ; Cuncao WU ; Jinshan HE ; Long WANG ; Xuebin LI
Chinese Circulation Journal 2025;40(2):170-174
Objectives:To analyze the clinical characteristics,strategies,success and complication rates of lead extraction and re-implantation during the upgrade of cardiovascular implantable electronic devices(CIED)in non-infectious patients.Methods:This retrospective study collected and analyzed the baseline clinical data and surgical data of 66 non-infected patients who had their existing CIEDs(including cardiac pacemaker,implantable cardioverter defibrillator[ICD],cardiac resynchronization therapy pacemaker[CRT-P])upgraded to ICD or CRT-P or cardiac resynchronization therapy defibrillator(CRT-D)or subcutaneous implantable cardioverter defibrillator(S-ICD)in Peking University People's Hospital from March 2018 to March 2024.We analyzed the strategies of lead extraction and reimplantation as well as the operation success rate and complication rate.Results:Among the 66 patients,preoperative imaging revealed that 12 patients(18.2%)had severe stenosis/occlusion of the venous access route,with lead wear/perforation in 26 patients(39.4%).32 patients(48.5%)underwent transvenous lead extraction(TLE),of which all leads were removed in 27 patients(84.4%),and only non-functional leads were removed in 5 patients(15.6%).The success rate of the TLE procedure was 100%and no complication occurred.Among the 66 patients,functional leads retained and new leads were implanted on the same side in 28 patients(42.4%),all leads were removed and new leads were reimplanted on the opposite side in 22 patients(33.3%),only non-functional leads were removed and new leads were reimplanted on the same side in 5 patients(7.6%),all leads were removed and new leads were reimplanted on the same side in 5 patients(7.6%),and 6 patients(9.1%)had the leads abandoned and then were re-implanled.The success rate of the upgrade surgery was 100%,no complications were reported.Conclusions:When the existing CIEDs(including cardiac pacemaker,ICD,CRT-P)of non-infected patients are upgraded to ICD,CRT-P,CRT-D or S-ICD,lead extraction and reimplantation are safe and feasible,and reimplantation can be performed on the ipsilateral or contralateral side.
9.Effect of different decompression methods on unilateral biportal endoscopy in the treatment of elderly patients with severe lumbar spinal stenosis
Zhi-long ZHANG ; Hai-ying WANG ; Feng-hua MA ; Yan-jie HOU
Journal of Regional Anatomy and Operative Surgery 2025;34(9):780-784
Objective To investigate the effect of different decompression methods on the efficacy of the unilateral biportal endoscopy(UBE)in the treatment of severe lumbar spinal stenosis(LSS).Methods A total of 203 elderly patients with LSS who underwent UBE treatment in our hospital from September 2021 to June 2024 were selected and divided into the unilateral group(102 cases)and the bilateral group(101 cases)according to different decompression methods.The unilateral group underwent unilateral decompression during operation,while the bilateral group underwent bilateral decompression(with bilateral decompression through the same incision and unilateral approach)during operation.The perioperative conditions,anatomical image parameters,visual analogue scale(VAS)scores,Oswestry disability index(ODI),and complications were compared between the two groups.The rehabilitation progress and complications of patients with different Charlson comorbidity index(CCI)values were compared.Results The operation time of patients in the bilateral group was longer than that in the unilateral group(P<0.05).The dural sac area and lumbar spinal canal area of patients in the bilateral group were larger than those in the unilateral group immediately after operation and 3 months after operation(P<0.05).The VAS scores and ODI 7 days and 3 months after operation of patients in the bilateral group were lower than those in the unilateral group(P<0.05).There was no statistically significant difference in the total incidence of complications between the two groups of patients(P>0.05).The first time of getting out of bed after operation and hospital stay in patients with CCI value>2 scores were longer than those in patients with CCI value≤2 scores(P<0.05).Conclusion Compared with unilateral decompression,bilateral decompression for elderly patients with severe LSS takes a longer surgical time,but it can better restore lumbar shape,alleviate pain,improve lumbar function,and has higher safety,and the milder the patient's condition,the faster the postoperative recovery.
10.Simultaneous management of transcatheter aortic valve replacement and transcatheter mitral valve edge-to-edge repair for a case of aortic regurgitation combined mitral valve prolapse
Yun-long MA ; Rui-feng LI ; Ming-jun HE ; Shun WANG ; Xiao-zhen ZHUO ; Ke HAN
Chinese Journal of Interventional Cardiology 2025;33(10):588-593
Aortic regurgitation and mitral regurgitation are more common in elderly heart valve disease,and both may be present in some patients.Severe aortic regurgitation complicated with severe mitral regurgitation often requires surgical valve replacement,but in patients at high risk of surgery,the risk of perioperative mortality is significantly increased.Therefore,for such patients,minimally invasive interventions can significantly improve long-term patient outcomes while reducing surgical risk.This article report a case of transcatheter aortic valve replacement combined with transcatheter edge-to-edge repair in the treatment of severe aortic regurgitation combined with mitral valve prolapse,in order to explore new treatment ideas for similar cases.

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