1.Mechanism of NAFLD-associated Intestinal Barrier Damage and Traditional Chinese Medicine Intervention Strategies Based on "Turbid Pathogenic Factors Entering the Blood" Theory
Haoyang QIN ; Lei LUO ; Mengge LI ; Xueqian KONG ; Fanghua ZHANG ; Zhongqin DANG ; Zhibo DANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):277-287
Intestinal barrier damage is a prominent feature of non-alcoholic fatty liver disease (NAFLD) and serves as a critical factor driving the progression from simple fatty liver to non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. The "turbid pathogenic factors entering the blood" theory integrates classical traditional Chinese medicine (TCM) principles with contemporary disease evolution trends and research findings. It posits that endogenous turbid pathogenic factors within the body infiltrate the blood vessels, leading to impure and viscous blood quality, thereby triggering various diseases. Based on this theory, this article elucidated the pathogenic mechanism of NAFLD-associated intestinal barrier damage. It argued that in NAFLD, the liver loses its dredging function, and the spleen becomes obstructed and dysfunctional. Moreover, essential nutrients fail to be properly transformed, resulting in the internal generation of turbid pathogenic factors. This subsequently initiates a series of pathological changes, namely, "infiltration of phlegm-turbidity into the blood, eroding the intestinal mucosa", "infiltration of glucose-turbidity into the blood, macerating and eroding the intestinal mucosa", "infiltration of heat-turbidity into the blood, scorching and eroding the intestinal mucosa", and "infiltration of stasis-turbidity into the blood, stagnating and eroding the intestinal mucosa", ultimately causing intestinal barrier damage. Furthermore, guided by the "turbid pathogenic factors entering the blood" theory, this article explored TCM intervention strategies: employing medicinals targeting the liver meridian to address the root cause and reduce the generation and deposition of turbid pathogenic factors in the liver, administering blood-system medicinals to clear the blood and purge turbidity, thereby intercepting the progression of the disease mechanism, and applying tonifying medicinals to bolster healthy Qi and defend against turbid invasion, allowing the damaged intestinal mucosa to gradually heal. This article presented novel theoretical and medicinal perspectives for analyzing NAFLD-associated intestinal barrier damage based on the "turbid pathogenic factors entering the blood" theory, aiming to provide new entry points and broader horizons for related research and clinical practice.
2.Molecular Mechanism of Programmed Cell Death in Chronic Obstructive Pulmonary Disease and Traditional Chinese Medicine Intervention: A Review
Xin PENG ; Yunhui LI ; Lei LIANG ; Zheyu LUAN ; Hanxiao WANG ; Haotian XU ; Ziming DANG ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):304-313
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that poses a significant threat to global health, exhibiting high morbidity, disability and mortality rate, with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex, and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death (PCD) is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine (TCM) is characterized by holistic regulation. In recent years, extensive research has been conducted in the TCM field focusing on modulating apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis for the treatment of COPD, yielding remarkable achievements. Therefore, this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD, aiming to provide insights and references for the clinical prevention, treatment and in-depth research of COPD.
3.Molecular Mechanism of Programmed Cell Death in Chronic Obstructive Pulmonary Disease and Traditional Chinese Medicine Intervention: A Review
Xin PENG ; Yunhui LI ; Lei LIANG ; Zheyu LUAN ; Hanxiao WANG ; Haotian XU ; Ziming DANG ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):304-313
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease that poses a significant threat to global health, exhibiting high morbidity, disability and mortality rate, with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex, and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death (PCD) is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine (TCM) is characterized by holistic regulation. In recent years, extensive research has been conducted in the TCM field focusing on modulating apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis for the treatment of COPD, yielding remarkable achievements. Therefore, this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD, aiming to provide insights and references for the clinical prevention, treatment and in-depth research of COPD.
4.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
5.Effect of Acupuncture at Neiguan (PC6) on Improving Autism by Promoting Myelination Through The METTL14/m⁶A/PTEN Axis Based on “Xuanfu-Suiqiao” Theory
Wei-Li DANG ; Lü-Yuan LIANG ; Yu-Xin LI ; Zhi-Yao LI ; Sai-Dan LIU ; Jia-Lei CAO ; Rong-Ze MA ; Yun-Kai WANG ; Xiao-Qing YANG ; Bing-Qi WEI ; Bing-Xiang MA
Progress in Biochemistry and Biophysics 2026;53(5):1165-1177
ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m6A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m6A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m6A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.
6.Mechanisms of Metabolic Imbalance in MAFLD with T2DM from Theory of Middle Energizer Acting as a Balance and Traditional Chinese Medicine Intervention Strategies
Haoyang QIN ; Mengge LI ; Lei LUO ; Xueqian KONG ; Fanghua ZHANG ; Zhongqin DANG ; Zhibo DANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):244-253
Metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) have a high comorbidity rate, emerging as a major global public health issue. The concept that the middle energizer acting as a balance refers to the role of the middle energizer in maintaining the balance of Qi and blood, dryness and dampness, as well as water and fire (Yin and Yang) in the human body. The core feature of MAFLD with T2DM is the metabolic imbalance, which is closely related to the dysfunction of the middle energizer's balancing role. This article explores the mechanisms of metabolic imbalance in MAFLD with T2DM from the perspective of the middle energizer acting as a balance, proposing that middle energizer dysfunction is the root cause. Qi movement, dryness-dampness, and ministerial fire are the two ends of the balance. MAFLD with T2DM is accompanied by various seemingly contradictory pathological states and imbalances, such as "Qi stagnation and failure of free movement vs. Qi dispersion without retention", "damp-turbidity obstruction vs. internal dryness and fluid consumption", and "ministerial fire decline vs. hyperactivity and scorching". On this basis, the traditional Chinese medicine (TCM) intervention strategies and their microscopic mechanisms are discussed. For the root cause of middle energizer imbalance, wind-dispelling herbs and Qi-replenishing and middle energizer-invigorating herbs are used to restore the balancing role of the middle energizer (delaying glucose and lipid absorption, restoring intestinal homeostasis, and ameliorating insulin resistance in skeletal muscle and adipocytes). For the secondary imbalances, pungent-dispersing and liver-soothing herbs combined with sour-astringent herbs are used to balance Qi movement (alleviating mitochondrial dysfunction in hepatocytes and impaired glucose transport in tissue cells). Bitter-warm and dampness-draining herbs combined with sweet-cold and moistening herbs are used to balance dryness and dampness (reducing hepatic steatosis, cellular hyperosmotic dehydration, and intracellular metabolic disorders). Yang-lifting and warm-invigorating herbs combined with clearing-descending and Yin-nourishing herbs are used to balance ministerial fire (ameliorating hepatocyte apoptosis and liver fibrosis processes and alleviating systemic chronic inflammation and related damage). According to the theory of the middle energizer acting as a balance, this article explores the mechanisms of metabolic imbalance in MAFLD with T2DM and TCM intervention strategies, providing new insights and a framework for related scientific research and clinical practice.
7.Mechanisms of Metabolic Imbalance in MAFLD with T2DM from Theory of Middle Energizer Acting as a Balance and Traditional Chinese Medicine Intervention Strategies
Haoyang QIN ; Mengge LI ; Lei LUO ; Xueqian KONG ; Fanghua ZHANG ; Zhongqin DANG ; Zhibo DANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):244-253
Metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) have a high comorbidity rate, emerging as a major global public health issue. The concept that the middle energizer acting as a balance refers to the role of the middle energizer in maintaining the balance of Qi and blood, dryness and dampness, as well as water and fire (Yin and Yang) in the human body. The core feature of MAFLD with T2DM is the metabolic imbalance, which is closely related to the dysfunction of the middle energizer's balancing role. This article explores the mechanisms of metabolic imbalance in MAFLD with T2DM from the perspective of the middle energizer acting as a balance, proposing that middle energizer dysfunction is the root cause. Qi movement, dryness-dampness, and ministerial fire are the two ends of the balance. MAFLD with T2DM is accompanied by various seemingly contradictory pathological states and imbalances, such as "Qi stagnation and failure of free movement vs. Qi dispersion without retention", "damp-turbidity obstruction vs. internal dryness and fluid consumption", and "ministerial fire decline vs. hyperactivity and scorching". On this basis, the traditional Chinese medicine (TCM) intervention strategies and their microscopic mechanisms are discussed. For the root cause of middle energizer imbalance, wind-dispelling herbs and Qi-replenishing and middle energizer-invigorating herbs are used to restore the balancing role of the middle energizer (delaying glucose and lipid absorption, restoring intestinal homeostasis, and ameliorating insulin resistance in skeletal muscle and adipocytes). For the secondary imbalances, pungent-dispersing and liver-soothing herbs combined with sour-astringent herbs are used to balance Qi movement (alleviating mitochondrial dysfunction in hepatocytes and impaired glucose transport in tissue cells). Bitter-warm and dampness-draining herbs combined with sweet-cold and moistening herbs are used to balance dryness and dampness (reducing hepatic steatosis, cellular hyperosmotic dehydration, and intracellular metabolic disorders). Yang-lifting and warm-invigorating herbs combined with clearing-descending and Yin-nourishing herbs are used to balance ministerial fire (ameliorating hepatocyte apoptosis and liver fibrosis processes and alleviating systemic chronic inflammation and related damage). According to the theory of the middle energizer acting as a balance, this article explores the mechanisms of metabolic imbalance in MAFLD with T2DM and TCM intervention strategies, providing new insights and a framework for related scientific research and clinical practice.
8.Research frontiers and hotspots of carbon nanomaterials in biomedical field over the past 10 years
Xiaowen DANG ; Hailiang HUANG ; Lei HUANG ; Yajie WANG
Chinese Journal of Tissue Engineering Research 2025;29(4):752-760
BACKGROUND:Research on carbon nanomaterials in the biomedical field is booming,and related scientific research results are increasing year by year.However,visualization analysis of the annual number of publications,the research status of countries,institutions,authors,and research hotspots and trends in this field is relatively scarce. OBJECTIVE:To present the research status of carbon nanomaterials in biomedical field,reveal the main research subjects,explore the research hotspots and development trends,and provide a reference for the future development of this field. METHODS:The core data set of Web of Science was used as the literature source to search the relevant researches on carbon nanomaterials in the biomedical field from 2012 to 2023.The knowledge map was generated by using Citespace software with countries,institutions,authors,keywords,and co-citations as nodes and for visualization analysis. RESULTS AND CONCLUSION:(1)A total of 2 932 papers were included in this study.In the medical field,carbon nanomaterials had a large number of papers and a fast growth rate.The United States has a large number of papers;China is an emerging force in this field,although the number of papers is the largest,but the level of research and influence need to be improved.The Chinese Academy of Sciences is the largest cooperative network institution,which mainly targets domestic institutions and lacks cooperation with well-known foreign institutions.(2)Keyword analysis displays that the green synthesis method and application of displaying carbon points have been the focus of research,followed by the new method of combining carbon nanomaterials with cancer phototherapy and immunotherapy,the key direction of future research.(3)The dynamic development trend of co-citations suggests that tissue engineering is a hot research topic of carbon nanomaterials in the field of biomedicine,mainly including the research of carbon nanomaterials for the repair and regeneration of heart and nerve tissue and as a bio-ink additive for 3D and 4D bioprinting.(4)In the future,with the development of the biomedical field in the direction of precision and treatment,researchers should speed up the creation of carbon-based systems formed by the combination of scientific and effective carbon nanomaterials with science and technology,new polymers or organic molecules,and new therapeutic methods,so as to give full play to the maximum effect of carbon nanomaterials.
9.Research progress in the fungal bioluminescence pathway.
Lei LÜ ; Ke CHENG ; Zhitao XU ; Shijie AN ; Dang XU ; Hao DU
Chinese Journal of Biotechnology 2025;41(7):2545-2558
The fungal bioluminescence pathway (FBP) catalyzes the oxidation of endogenous caffeic acid to produce green bioluminescence through an enzymatic cascade. Genetic engineering of FBP into plants creates autoluminescent specimens that circumvent the substrate limitations of conventional reporter systems. These transgenic plants serve dual functions as aesthetic displays and versatile biosensing platforms, enabling applications in real-time gene expression monitoring, continuous environmental surveillance, and non-invasive bioimaging, offering novel opportunities for horticultural production, environmental conservation, and bioengineering applications. This review synthesizes current advances in plant FBP engineering and explores how machine learning approaches can optimize autoluminescent phenotypes, thereby accelerating innovation in agricultural biotechnology, environmental sensing, and synthetic biology applications.
Fungi/genetics*
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Plants, Genetically Modified/metabolism*
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Genetic Engineering
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Biosensing Techniques
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Luminescent Measurements
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Caffeic Acids/metabolism*
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Luminescence
10.Causal relationship between immune cells and myopia:a two-sample bidirec-tional and multivariable Mendelian randomization analysis
Xueting WANG ; Yalong DANG ; Fang LEI
Recent Advances in Ophthalmology 2025;45(3):221-226
Objective To explore the causal relationship between myopia and specific immune cells through Mende-lian randomization(MR)analysis.Methods Data were mined from the Genome-Wide Association Studies(GWAS)data-base,and 731 immune cell characteristics were selected as exposure factors and myopia as the outcome factor.A signifi-cance threshold was established to filter single nucleotide polymorphisms(SNPs)significantly associated with immune cells and myopia,and the influence of weak instrument variable bias was eliminated.The primary analysis method employed was the inverse variance weighted(IVW)approach,supplemented by simple mode,weighted median,weighted mode,and MR-Egger regression for data analysis.The causal relationship between circulating immune cells and myopia was assessed using odds ratios(OR)and 95%confidence intervals.For the SNPs of immune cells that met the hypothesis,Cochran's Q test was used to evaluate heterogeneity,and MR-Egger regression and MR-PRESSO methods were employed to exclude hor-izontal pleiotropy.The leave-one-out analysis was utilized to assess whether significant results were driven by individual SNPs.To avoid reverse causal relationships,myopia was taken as the exposure variable and immune cell phenotypes as outcome variables in the reverse MR analysis.Additionally,multivariate Mendelian randomization(MVMR)was used to e-valuate the causal and independent effects of these immune cells on myopia.Results(1)The results from the two-sam-ple MR IVW method indicated that Memory B cell AC and CD24+CD27+AC(B cells)were protective factors against my-opia.In contrast,Naive CD8br%CD8br(T cells),CD39+CD8br AC(T cells),CD25 on CD39+activated Treg(T cells),PDL-1 on CD 14+CD 16+monocytes and CD80 on myeloid DC were identified as risk factors for myopia.These re-sults are consistent with those of MR-Egger and other methods.MR-Egger regression and MR-PRESSO analyses demonstra-ted that there was no horizontal pleiotropy(P>0.05).(2)The reverse two-sample MR analysis revealed no bidirectional causal relationships between myopia and the aforementioned seven immune cells(all P>0.05).(3)In the MVMR analysis,the significant causal relationship between CD80 on myeloid DC and myopia remained robust after adjusting for potential confounding variables.Conclusion This study reveals the complex causal relationships between various immune pheno-types and myopia through genetic methods,and demonstrates the intricate regulatory patterns of interactions between the immune system and myopia.

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