1.Immunity-inflammation Mechanism of Viral Pneumonia and Traditional Chinese Medicine Treatment Based on Theory of Healthy Qi and Pathogenic Qi
Zheyu LUAN ; Hanxiao WANG ; Xin PENG ; Yihao ZHANG ; Yunhui LI ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):239-247
Viral pneumonia is an infectious disease caused by virus invading the lung parenchyma and interstitial tissue and causing lung inflammation, with the incidence rising year by year. Traditional Chinese medicine (TCM) can treat viral pneumonia in a multi-component, multi-target, and holistic manner by targeting the core pathogenesis of pneumonia caused by different respiratory viruses, demonstrating minimal side effects and significant advantages. According to the theory of healthy Qi and pathogenic Qi in TCM, the struggle between healthy Qi and pathogenic Qi and the imbalance between immunity and inflammation run through the entire process of viral pneumonia, and the immunity-inflammation status at different stages of the disease reflects different relationships between healthy Qi and pathogenic Qi. Immune dysfunction leads to the deficiency of healthy Qi, causing viral infections. The struggle between healthy Qi and pathogenic Qi causes immunity-inflammation imbalance, leading to the onset of viral pneumonia. Inflammatory damage causes persistent accumulation of phlegm and stasis, leading to the progression of viral pneumonia. The cytokine storm causes immunodepletion, leading to the excess of pathogenic Qi and diminution of healthy Qi and the deterioration of viral pneumonia. After the recovery from viral pneumonia, there is a long-term imbalance between immunity and micro-inflammation, which results in healthy Qi deficiency and pathogenic Qi lingering. Healthy Qi deficiency and pathogenic Qi excess act as common core causes of pneumonia caused by different respiratory viruses. Clinical treatment should emphasize both replenishing healthy Qi and eliminating pathogenic Qi, helping to restore the balance between healthy Qi and pathogenic Qi as well as between immunity and inflammation, thus promoting the recovery of patients from viral pneumonia. According to the TCM theory of healthy Qi and pathogenic Qi, this article summarizes the immunity-inflammation mechanisms at different stages of viral pneumonia, and explores the application of the method of replenishing healthy Qi and eliminating pathogenic Qi in viral pneumonia. The aim is to probe into the scientific connotation of the TCM theory of healthy Qi and pathogenic Qi in viral pneumonia and provide ideas for the clinical application of the method of replenishing healthy Qi and eliminating pathogenic Qi to assist in the treatment of viral pneumonia.
2.Thoughts of Syndrome Differentiation and Treatment and Effect Mechanism of Haoqin Qingdantang in Treating Viral Pneumonia Based on Theory of Treating Different Diseases with Same Therapy
Xin PENG ; Haotian XU ; Lei LIANG ; Zheyu LUAN ; Hanxiao WANG ; Yihao ZHANG ; Kun YANG ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):209-217
The principle of treating different diseases with the same therapy is the essence of syndrome differentiation and treatment in traditional Chinese medicine (TCM). It means that when the same pathogenic changes or the same symptoms appear in the development of different diseases, the same principles or methods can be used for treatment. Due to the complexity and high variability of viral pathogenicity, the precise and effective treatment of different types of viral pneumonia (VP) has always been a research focus and difficulty in modern medicine. VP belongs to the category of external-contraction febrile disease, warm disease, and epidemic in TCM. Haoqin Qingdantang (HQQDD) is a representative formula for clearing heat and dispelling dampness in warm diseases, and its intervention in VP caused by various viral infections has significant effects. This study, guided by the theory of treating different diseases with the same therapy, links the related studies on using HQQDD to treat different types of VP and finds that influenza virus pneumonia (IVP), severe acute respiratory syndrome (SARS), and COVID-19 all have a common pathogenic mechanism of dampness-heat at different stages of respective diseases. When these diseases are dominated by damp-heat factors, the use of HQQDD yields remarkable therapeutic effects. Modern pharmacological studies have confirmed that HQQDD can inhibit virus replication, reduce fever reactions, inhibit the expression of inflammatory mediators, and regulate immune balance. Moreover, the sovereign medicine in this formula has excellent antiviral activity, and the formula reflects rich scientific connotations of treating VP. According to the theory of treating different diseases with the same therapy and based on the effective treatment practice and modern pharmacological research of HQQDD for different types of VP, this paper mines the underlying TCM theory of treatment with the same therapy, explores the syndrome differentiation and treatment strategy and effect mechanism of this formula for different types of VP, and analyzes the treatment mechanism and characteristics, with the aim of providing evidence and reference for the clinical application and modern research of HQQDD.
3.Role of Traditional Chinese Medicine in Regulating Immune Inflammation and Microvascular Damage in Preventing Recurrence of Pneumonia During Recovery Based on Combination of Pathogenic Factors
Xin PENG ; Haotian XU ; Lei LIANG ; Zheyu LUAN ; Hanxiao WANG ; Kun YANG ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):249-258
Pneumonia is an infectious disease with high morbidity and mortality worldwide, and its damage to the body is not limited to the acute phase. The theory of combination of pathogenic factors emphasizes that the combination of new pathogens and residual pathogens in the body leads to the occurrence of diseases, which generalizes the causes of recurrence during pneumonia recovery. During the recovery stage of pneumonia, pathological changes such as disturbance of immune homeostasis, persistent low-grade inflammation, and microvascular damage continue to affect the body function, impair the health and quality of life of patients, and increase the risk of secondary infection. According to the theory of traditional Chinese medicine (TCM), pneumonia is caused by deficiency, and Qi deficiency and blood stasis is the core pathogenesis in the recovery stage. At this time, the body is not full of healthy qi and still has residual pathogens, and thus it is susceptible to external pathogenic factors that lead to disease recurrence. As an important part of the TCM philosophy of treating disease before its onset, prevention of recurrence after recovery emphasizes the need for aftercare in the recovery stage to prevent disease recurrence. Based on the pathogenesis theory of combination of pathogenic factors and the pathogenesis of Qi deficiency and blood stasis, this paper discusses the effect and connotation of TCM in regulating immune inflammation and microvascular damage in preventing recurrence of pneumonia during the recovery stage, aiming to develop new ideas for effective prevention and treatment of pneumonia at this stage.
4.Prospects for 3D Bioprinting Research and Transdisciplinary Application to Preclinical Animal Models
Min HU ; Lexuan DONG ; Yi GAO ; Ziqi XI ; Zihao SHEN ; Ruiyang TANG ; Xin LUAN ; Min TANG ; Weidong ZHANG
Laboratory Animal and Comparative Medicine 2025;45(3):318-330
Animal experiments are widely used in biomedical research for safety assessment, toxicological analysis, efficacy evaluation, and mechanism exploration. In recent years, the ethical review system has become more stringent, and awareness of animal welfare has continuously increased. To promote more efficient and cost-effective drug research and development, the United States passed the Food and Drug Administration (FDA) Modernization Act 2.0 in September 2022, which removed the federal mandate requiring animal testing in preclinical drug research. In April 2025, the FDA further proposed to adopt a series of "new alternative methods" in the research and development of drugs such as monoclonal antibodies, which included artificial intelligence computing models, organoid toxicity tests, and 3D micro-physiological systems, thereby gradually phasing out traditional animal experiment models. Among these cutting-edge technologies, 3D bioprinting models are a significant alternative and complement to animal models, owing to their high biomimetic properties, reproducibility, and scalability. This review provides a comprehensive overview of advancements and applications of 3D bioprinting technology in the fields of biomedical and pharmaceutical research. It starts by detailing the essential elements of 3D bioprinting, including the selection and functional design of biomaterials, along with an explanation of the principles and characteristics of various printing strategies, highlighting the advantages in constructing complex multicellular spatial structures, regulating microenvironments, and guiding cell fate. It then discusses the typical applications of 3D bioprinting in drug research and development,including high-throughput screening of drug efficacy by constructing disease models such as tumors, infectious diseases, and rare diseases, as well as conducting drug toxicology research by building organ-specific models such as those of liver and heart. Additionally,the review examines the role of 3D bioprinting in tissue engineering, discussing its contributions to the construction of functional tissues such as bone, cartilage, skin, and blood vessels, as well as the latest progress in regeneration and replacement. Furthermore, this review analyzes the complementary advantages of 3D bioprinting models and animal models in the research of disease progression, drug mechanisms, precision medicine, drug development, and tissue regeneration, and discusses the potential and challenges of their integration in improving model accuracy and physiological relevance. In conclusion, as a cutting-edge in vitro modeling and manufacturing technology, 3D bioprinting is gradually establishing a comprehensive application system covering disease modeling, drug screening, toxicity prediction, and tissue regeneration.
5.Prospects for 3D Bioprinting Research and Transdisciplinary Application to Preclinical Animal Models
Min HU ; Lexuan DONG ; Yi GAO ; Ziqi XI ; Zihao SHEN ; Ruiyang TANG ; Xin LUAN ; Min TANG ; Weidong ZHANG
Laboratory Animal and Comparative Medicine 2025;45(3):318-330
Animal experiments are widely used in biomedical research for safety assessment, toxicological analysis, efficacy evaluation, and mechanism exploration. In recent years, the ethical review system has become more stringent, and awareness of animal welfare has continuously increased. To promote more efficient and cost-effective drug research and development, the United States passed the Food and Drug Administration (FDA) Modernization Act 2.0 in September 2022, which removed the federal mandate requiring animal testing in preclinical drug research. In April 2025, the FDA further proposed to adopt a series of "new alternative methods" in the research and development of drugs such as monoclonal antibodies, which included artificial intelligence computing models, organoid toxicity tests, and 3D micro-physiological systems, thereby gradually phasing out traditional animal experiment models. Among these cutting-edge technologies, 3D bioprinting models are a significant alternative and complement to animal models, owing to their high biomimetic properties, reproducibility, and scalability. This review provides a comprehensive overview of advancements and applications of 3D bioprinting technology in the fields of biomedical and pharmaceutical research. It starts by detailing the essential elements of 3D bioprinting, including the selection and functional design of biomaterials, along with an explanation of the principles and characteristics of various printing strategies, highlighting the advantages in constructing complex multicellular spatial structures, regulating microenvironments, and guiding cell fate. It then discusses the typical applications of 3D bioprinting in drug research and development,including high-throughput screening of drug efficacy by constructing disease models such as tumors, infectious diseases, and rare diseases, as well as conducting drug toxicology research by building organ-specific models such as those of liver and heart. Additionally,the review examines the role of 3D bioprinting in tissue engineering, discussing its contributions to the construction of functional tissues such as bone, cartilage, skin, and blood vessels, as well as the latest progress in regeneration and replacement. Furthermore, this review analyzes the complementary advantages of 3D bioprinting models and animal models in the research of disease progression, drug mechanisms, precision medicine, drug development, and tissue regeneration, and discusses the potential and challenges of their integration in improving model accuracy and physiological relevance. In conclusion, as a cutting-edge in vitro modeling and manufacturing technology, 3D bioprinting is gradually establishing a comprehensive application system covering disease modeling, drug screening, toxicity prediction, and tissue regeneration.
6.Pathogenesis of Airway Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Intervention of Traditional Chinese Medicine: A Review
Xin PENG ; Jian LIU ; Zheyu LUAN ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):228-239
Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases of the respiratory system in the clinic. The disease has a long course and is difficult to cure, which seriously threatens human health. Airway mucus hypersecretion (AMH) is an independent risk factor for COPD and has a significant impact on the development and prognosis of the disease. The review finds that the abnormal proliferation of goblet cells and the excessive secretion of mucin are the direct causes of AMH. The pathogenesis of AMH may be closely related to the inhalation of heterogeneous particles, airway inflammation, the imbalance of mucin/water salt ratio, and the regulation of related signaling pathways. Traditional Chinese medicine (TCM) believes that AMH of COPD belongs to the category of lung distension with phlegm-fluid retention syndrome, and the disease is mainly treated from phlegm on the basis of lung distension. This article summarizes the relevant research in the field of TCM in recent years and finds that the single TCM that effectively intervened AMH of COPD is mainly phlegm-resolving TCM, and the main active ingredients of TCM are flavonoids, terpenoids, phenols, and alkaloids. The main TCM compounds are mainly designed to remove heat-phlegm, warmly resolve cold-phlegm, dry dampness to eliminate phlegm, invigorate Qi, promote blood circulation and dispel phlegm, and invigorate lung, spleen, and kidney. Its mechanism of action may be direct inhibition or indirect inhibition of airway epithelial goblet cell metaplasia and mucin expression by inhibiting airway inflammation, regulating aquaporins to correct the imbalance of mucin/water salt ratio, and regulating signaling pathways, so as to reduce mucus oversecretion in COPD. However, there are still some problems. For example, the research mainly focuses on TCM compounds instead of the single TCM or its effective components. The research on the mechanism of action is not thorough enough, and the research results are not interoperable. The clinical transformation rate of basic research is insufficient. This article systematically reviews the research status of AMH in the treatment of COPD with TCM and puts forward some thoughts on the existing problems, so as to provide a reference for clinical rational medication and in-depth research.
7.Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy.
Yongchun PAN ; Xiaowei LUAN ; Fei ZENG ; Xuyuan WANG ; Shurong QIN ; Qianglan LU ; Guanzhong HE ; Yanfeng GAO ; Xiaolian SUN ; Xin HAN ; Bangshun HE ; Yujun SONG
Acta Pharmaceutica Sinica B 2024;14(2):795-807
Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.
8.Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" Acta Pharm Sin B (2022) 4224-4234.
Zekun LI ; Yongchun PAN ; Shiyu DU ; Yayao LI ; Chao CHEN ; Hongxiu SONG ; Yueyao WU ; Xiaowei LUAN ; Qin XU ; Xiaoxiang GUAN ; Yujun SONG ; Xin HAN
Acta Pharmaceutica Sinica B 2024;14(2):897-899
[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].
9.Discussion on Traditional Chinese Medicine Theory and Pharmacological Mechanism of Xuanfei Baidu Prescription in Treatment of Viral Pneumonia
Yihao ZHANG ; Xin PENG ; Zheyu LUAN ; Yunfan WANG ; Jiaqi SHANG ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):214-224
Viral pneumonia (VP) is an inflammatory disease caused by one or more viruses that infect the upper respiratory tract and spread downward. Causing varying degrees of pulmonary parenchymal damage, VP poses a serious threat to the society and public health. The treatment of VP now faces the dilemma of drug shortage, since Western medicine can only alleviate symptoms and lacks specific treatment methods. In traditional Chinese medicine (TCM), VP is assigned as an epidemic disease, with the etiology attributed to epidemic toxin and six excesses and the pathological factors of dampness, heat, toxin, deficiency, and stasis. The basic pathogenesis of VP is Yin-Yang imbalance, dysfunction of Zang-Fu organs, and healthy Qi deficiency. Accordingly, the treatment should follow the principle of replenishing healthy Qi and expelling pathogen. The treatment method of VP is mainly developed based on syndrome differentiation of six meridians, defense-Qi-nutrient-blood, and triple energizer. Xuanfei Baidu prescription (XFBD) is an effective prescription developed by Academician ZHANG Boli and Professor LIU Qingquan by literature research and selection of multi-component Chinese medicine. It is the product of modern research combined with TCM. XFBD is modified from Maxing Shigantang, Maxing Yigantang, Tingli Dazao Xiefeitang, Qianjin Weijingtang, and Buhuanjin Zhengqisan. It is mainly used to treat epidemic diseases with the syndrome of dampness toxin stagnating in the lung, with the effects of ventilating lung and resolving dampness, clearing heat and expelling pathogen, purging lung, and removing toxin, demonstrating the potential for the prevention and treatment of VP. This paper reviews the research progress of XFBD in combating VP in terms of the prescription composition, compatibility ideas, indications, and clinical new applications, as well as the pharmacological mechanisms of inhibiting virus, reducing inflammation, regulating immune system, ameliorating pulmonary fibrosis, and modulating intestinal flora. In addition, we put forward our thoughts and suggestions on the problems in the research, with a view to informing the clinical use of drugs and the basic research on the treatment of VP including COVID-19.
10.Effects of salvianolic acid B on anti-oxidative stress of umbilical cord mesenchymal stem cells
Yu-Ling LUAN ; Ling-Xiao ZHANG ; Xin-Yue DING ; Zong-Jun LIU
The Chinese Journal of Clinical Pharmacology 2024;40(10):1434-1437
Objective To investigate the effect of salvianolic acid B on the antioxidant stress capacity of human umbilical cord mesenchymal stem cells(HUCMSCs)and to improve the clinical application efficiency of mesenchymal stem cells.Methods The 5th generation HUMSCs were used for the experiment and divided into control group,model group,and experimental-L,-M,-H groups.The control group was cultured normally;the model group was treated with 800 μmol·L-1 hydrogen peroxide(H2 O2)for 2 h;and the experimental-L,-M,-H groups were pretreated with 2,10,20 μg·mL-1salvianolic acid B for 24 h before adding 800 μmol·L-1 H2 O2 for 2 h.The levels of glutathione(GSH),superoxide dismutase(SOD),and malondialdehyde(MDA)in the cell supernatant of each group were detected using test kits;real-time fluorescence quantitative reverse transcription polymerase chain reaction was used to detect the mRNA expression of apoptosis-related genes Caspase 1,and B-cell lymphoma-2(Bcl-2).Results After treatment with 800 μmol·L-1H2 O2 for 2 h,the levels of MDA in the cell supernatants of the control group,model group,and experimental-H group were(3.27±0.41),(6.50±0.21)and(4.79±0.40)nmol·mL-1,respectively;the GSH levels were(35.43±0.72),(20.13±0.58)and(32.30±3.87)μmoL·L-1;the SOD levels were(5.34±0.18),(3.34±0.20)and(5.09±0.15)U·mL-1;the expression of Caspase 1 mRNA were 1.02±0.21,2.78±0.26 and 2.37±0.32;the expression of Bcl-2 mRNA were 1.01±0.12,0.43±0.03 and 0.60±0.17.Compared with the control group,the above indexes in the model group were statistically significant(P<0.05,P<0.01).Compared with the model group,the above indexes in the experimental-H group were statistically significant(P<0.05,P<0.01).Conclusion Salvianolic acid B can reduce apoptosis caused by oxidative stress and enhance the antioxidant stress capacity of HUCMSCs.

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