1.Ameliorating Effect of Yifei Tongluo Prescription on Bleomycin-induced Pulmonary Fibrosis in Rats via Regulating NLRP3/Caspase-1/GSDMD Signaling Pathway and Epithelial-mesenchymal Transition
Bowen ZHOU ; Zefeng LI ; Xian MA ; Xuannian LI ; Jingwen WANG ; Fei XU ; Huaman LIU ; Xinhua JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):150-159
ObjectiveTo observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin D (GSDMD) pathway and epithelial-mesenchymal transition (EMT) in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley (SD) rats were randomly divided into a blank group, a model group, a prednisone acetate group (1.17 mg·kg-1), and low- and high-dose Yifei Tongluo prescription groups (10.62 and 21.24 g·kg-1, respectively). Administration started on the 7th day after modeling, once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression of α-smooth muscle actin (α-SMA) and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome, E-cadherin (E-cad), and typeⅠ collagen (ColⅠ) in lung tissues was detected by immunofluorescence. The content of hydroxyproline (HYP), tumor necrosis factor (TNF)-α, interleukin (IL)-18, and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), IL-1β, and transforming growth factor (TGF)-β1 in rat lung tissues were determined by real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of NLRP3, GSDMD, ASC, and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group, the model group exhibited a significantly increased lung coefficient (P<0.01) and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition, the levels of α-SMA, Vimentin, E-cad, and ColⅠ in lung tissues were significantly increased (P<0.01). The levels of fibrosis- and inflammation-related factors HYP, TNF-α, IL-18, and IL-1β in serum were significantly upregulated (P<0.01). The levels of factors related to the activation of NLRP3 inflammasome in lung tissues, including NLRP3, GSDMD, ASC, Caspase-1, IL-1β, and TGF-β1, were significantly upregulated (P<0.01). Compared with the model group, the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally, the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA, Vimentin, E-cad, and ColⅠ in lung tissue was significantly decreased (P<0.01). The levels of HYP, TNF-α, IL-18, and IL-1β in serum were significantly reduced (P<0.01). The expression levels of NLRP3, GSDMD, ASC, Caspase-1, IL-1β, and TGF-β1 in lung tissue were also significantly decreased (P<0.01). ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway, down-regulate release of pro-inflammatory and pro-fibrotic cytokines, alleviate NLRP3 inflammasome-mediated pyroptosis and EMT, and thereby improve pulmonary fibrosis in rats.
2.Research on the mechanism of Chaiqi yigan granules against liver cancer via the ferroptosis pathway
Bowen LIU ; Guiping MA ; Feng LI ; Xiaobin LI ; Fenping LU ; Xu PANG ; Shiping HU
China Pharmacy 2026;37(10):1272-1276
OBJECTIVE To explore the mechanism of Chaiqi yigan granules (CQYG) against liver cancer through the ferroptosis pathway. METHODS Network pharmacology combined with ferroptosis-related database was used to screen key targets and main effective components of CQYG against liver cancer via regulating ferroptosis; molecular docking technology was employed to analyze the binding ability of main active components to key targets. Human liver Huh-7 cells were divided into blank serum control (CON) group, CQYG drug-containing serum (CQYGKL) group, ferroptosis inducer (RSL3) group, mammalian target of rapamycin complex 1 (mTORC1) inhibitor (RMC-5552) group, mTORC1 agonist (CCT007093) group, and CCT007093+CQYGKL group. The levels of Fe 2+ , malondialdehyde (MDA), and glutathione (GSH) in the cells were detected in the former three groups; mRNA expressions of mammalian target of rapamycin (mTOR), sterol regulatory element-binding protein 1 (SREBP1), and stearoyl-CoA desaturase 1 (SCD1), protein expressions of SREBP1 and SCD1 as well as phosphorylation levels of mTOR and ribosomal S6 kinase (S6K) proteins were detected in all groups. RESULTS Key targets of CQYG for anti-liver cancer through the ferroptosis pathway were mTOR, SREBP1, SCD1,etc. The main active components included quercetin, tanshinone Ⅱ A , baicalein, etc. The binding energies of main active components to key targets were all less than -5 kJ/mol. Compared with CON group, the levels of Fe 2+ and MDA in the cells in CQYGKL group and RSL3 group were significantly increased, while the levels of GSH were significantly decreased ( P <0.05). mRNA expressions of mTOR, SREBP1 and SCD1, protein expressions of SREBP1 and SCD1, as well as the phosphorylation levels of mTOR and S6K proteins were significantly decreased in the CQYGKL group, RSL3 group, and RMC-5552 group, whereas all the above indicators were significantly increased in the CCT007093 group ( P <0.05). Compared with CCT007093 group, the changes in all the above indicators were significantly suppressed in the CCT007093+CQYGKL group ( P <0.05). CONCLUSIONS CQYG may induce ferroptosis by inhibiting mTORC1/SREBP1/SCD1 axis, thereby exerting anti-liver cancer effects.
3.Shenqi Buzhong Formula ameliorates mitochondrial dysfunction in a rat model of chronic obstructive pulmonary disease by activating the AMPK/SIRT1/PGC-1α pathway
Lu ZHANG ; Huanzhang DING ; Haoran XU ; Ke CHEN ; Bowen XU ; Qinjun YANG ; Di WU ; Jiabing TONG ; Zegeng LI
Journal of Southern Medical University 2025;45(5):969-976
Objective To explore the mechanism of Shenqi Buzhong(SQBZ)Formula for alleviating mitochondrial dysfunction in a rat model of chronic obstructive pulmonary disease(COPD)in light of the AMPK/SIRT1/PGC-1α pathway.Methods Fifty male SD rat models of COPD,established by intratracheal lipopolysaccharide(LPS)instillation,exposure to cigarette smoke,and gavage of Senna leaf infusion,were randomized into 5 groups(n=10)for treatment with saline(model group),SQBZ Formula at low,moderate and high doses(3.08,6.16 and 12.32 g/kg,respectively),or aminophylline(0.024 g/kg)by gavage for 4 weeks,with another 10 untreated rats as the control group.Pulmonary function of the rats were tested,and pathologies and ultrastructural changes of the lung tissues were examined using HE staining and transmission electron microscopy.The levels of SOD,ATP,MDA,and mitochondrial membrane potential in the lungs were detected using WST-1,colorimetric assay,TBA,and JC-1 methods.Flow cytometry was used to analyze ROS level in the lung tissues,and the protein expression levels of P-AMPKα,AMPKα,SIRTI,and PGC-1α were detected using Western blotting.Results The rat models of COPD showed significantly decreased lung function,severe histopathological injuries of the lungs,decreased pulmonary levels of SOD activity,ATP and mitochondrial membrane potential,increased levels of MDA and ROS,and decreased pulmonary expressions of P-AMPKα,SIRTI,and PGC-1α proteins.All these changes were significantly alleviated by treatment with SQBZ Formula and aminophylline,and the efficacy was comparable between high-dose SQBZ Formula group and aminophylline group.Conclusion SQBZ Formula ameliorates mitochondrial dysfunction in COPD rats possibly by activating the AMPK/SIRT1/PGC-1α pathway.
4.Application exploration of bidirectional regulation among meridian,time rhythm,and immune system in allergic rhinitis
Ke CHEN ; Bowen XU ; Xue LIANG ; Di WU ; Haoran XU ; Jie ZHU ; Jiabing TONG ; Zegeng LI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(6):833-838
Time rhythm and the immune system play crucial roles in the pathogenesis of allergic rhinitis.Traditional Chinese medicine(TCM)believes that the circulation of qi and blood in lung meridian follows the principle of"yang during the day,yin at night",which has a defensive function to protect the body from external pathogens.Qi stagnation in lung meridian and impaired qi and blood circulation can lead to the invasion of external pathogens,exacerbating allergic reactions,especially during the active period of the lung meridian,when the immune system is most sensitive to allergens.Based on this,this paper proposes the concept of"bidirectional regulation among meridian,time rhythm,and immune system",and in combination with TCM theory of midnight-noon and ebb-flow doctrine,analyzes the fluctuations of allergic rhinitis symptoms and the temporal changes of meridian qi and blood,and reveals the rhythmic relationship between meridian activity and immune response.This paper combines existing clinical and experimental studies to support this hypothesis,integrating the time dimension into traditional TCM syndrome differentiation and treatment,offering a more individualized treatment approach.This concept not only provides novel scientific evidence for TCM treatment of allergic rhinitis,but also offers theoretical support for optimizing treatment timing and intervention strategies.
5.Research progress on pyroptosis in subarachnoid hemorrhage
Bowen SUN ; Shuai LAN ; Xi'ao WANG ; Shancai XU ; Huaizhang SHI
Chinese Journal of Cerebrovascular Diseases 2025;22(5):349-355
Subarachnoid hemorrhage(SAH)is a major subtype of stroke,characterized by high mortality and disability rates.Pyroptosis,a form of programmed cell death,has been identified as a key pathological process in early brain injury.Current research indicates that pyroptosis can occur in neurons,microglia,astrocytes,and cerebral vascular endothelial cells after SAH,leading to neurological dysfunction,brain edema,and disruption of the blood-brain barrier.The NOD-like receptor protein 3(NLRP3)inflammasome is regarded as a central regulatory component of pyroptosis,and its activation mechanisms and roles in various cell types have become focal points of research.A variety of therapeutic strategies targeting this pathway have emerged,including NLRP3 inhibitors,Caspase-1 inhibitors,and Gasdermin-D inhibitors.The aforemenetioned approaches all have demonstrated efficacy in animal studies.Additionally,novel technologies such as stem cell therapy,exosome therapy,and gas therapy offer novel intervention approaches for modulating pyroptosis.Although,various therapeutic strategies targeting pyroptosis-related pathways have emerged in recent years,a comprehensive summary remains absent.This article reviewed the advancements in pyroptosis research following SAH and associated treatment strategies,aiming to provide a theoretical foundation for subsequent mechanistic studies and clinical translation.
6.Direction and clinical practice of traditional Chinese medicine in the prevention and treatment of cancer
Xinyi MA ; Bowen XU ; Jie LI ; Ying ZHANG ; Luchang CAO ; Yuansha GE ; Guanghui ZHU ; Xiaoyu ZHU ; Jingyuan WU ; Xinmiao WANG
Chinese Journal of Oncology 2025;47(2):121-128
Cancer is a major chronic disease that threatens human health, while traditional Chinese medicine (TCM) is a unique method for cancer prevention and treatment in China. After about 70 years of innovation and development, TCM has made constant progress in areas such as the clinical diagnosis, treatment, evidence-based researches, and mechanism exploration of cancer. It has special advantages in aspects such as reducing toxicity, enhancing treatment efficacy, managing symptoms, accelerating recovery, preventing recurrence and metastasis, and prolonging advanced-stage survival. However, there are still bottlenecks for TCM in cancer care. This paper cuts in the key links between TCM and western medicine in their combined application in cancer prevention and treatment, and take the original TCM theories on cancer as the lead, high-quality evidence-based researches as the drive, and analysis on the dynamic mechanism as the core, to show the advantages and effects of TCM in cancer treatment in an all-round way. It also aims to provide novel strategies for sustainable and innovative development and for formulation of comprehensive schemes that integrate TCM and western medicine for cancer prevention and treatment.
7.Fusobacterium nucleatum upregulates ABCG2 by activating the E-cadherin/β-catenin signaling pathway to promote oxaliplatin resistance in colorectal cancer
Fangqi XU ; Bowen LI ; Yang LIU ; Yunwei WEI
Chinese Journal of Oncology 2025;47(4):329-339
Objective:To investigate whether F.nucleatum affects the chemotherapy resistance of colorectal cancer by regulating ABC subfamily G subtype 2 (ABCG2), in view of the fact that the correlation between the two has not been reported. Methods:Oxaliplatin was used to interfere with colorectal cancer cells and co-cultured with F.nucleatum to establish a chemotherapy-induced model of microbial infection. Calcein AM/PI cell staining, trypan blue staining, and cell counting kit 8 (CCK-8) method were used to detect cell activity. Real-time fluorescence quantitative polymerase chain reaction and western blot were used to detect ABCG2 mRNA and protein expression levels in colorectal cancer cells. The target gene was knocked down by constructing shRNA plasmids. The HCT-116 cell F.nucleatum infection model was constructed and transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses were performed to determine the differential gene expression enrichment pathways. Genistein (GST) was used as an E-cadherin blocker, and triclabendazole sulfoxide (TCBZSO) was used as an ABCG2 blocker. Immunofluorescence was used to detect E-cadherin and β-catenin protein expressions and intracellular localization levels. The subcutaneous xenograft model of nude mice was constructed in vivo, and the expression level of ABCG2 protein in tissues was detected by immunohistochemical staining. Results:CCK-8 results showed that F. nucleatum+oxaliplatin group [HT-29, (92.26±1.66)%; HCT-116, (82.13±1.84)%] cell relative survival rate was higher than that of oxaliplatin group [HT-29, (79.64±3.72)%; HCT-116, (67.56±2.96)%; P<0.001]. The relative survival rate of oxaliplatin and F. nucleatum co-culture group with ABCG2-knockdown HCT-116 cells [(61.44±1.48)%] was lower than that of F. nucleatum and oxaliplatin co-cultured with HCT-116 cells [(69.29±4.45)%, P=0.015]. GO enrichment analysis showed that HCT-116 cells co-cultured with F.nucleatum were significantly enriched in "β-catenin binding", "cadherin binding" and "regulation of Wnt signaling pathway". RT-qPCR results showed that the relative expression of ABCG2 mRNA in F.nucleatum + genistein group was significantly lower than that in F.nucleatum group ( P<0.001). The results in vivo showed that the tumor weight in the F.n+L-OHP+TCBZSO group [(0.12±0.02)g] was lower than that in the F.n+L-OHP group [(0.33±0.05)g, P<0.001]. Immunohistochemistry suggested that the promotion of ABCG2 protein expression by F. nucleatum was blocked after TCBZSO intervention. Conclusion:F. nucleatum up-regulates ABCG2 expression through E-cadherin/β-catenin signaling pathway to promote colorectal cancer resistance to oxaliplatin.
8.Exploration on the Three-Stage Treatment System for Chronic Obstructive Pulmonary Disease Based on National TCM Master Han Mingxiang's"Qi Monism"
Bowen XU ; Ke CHEN ; Jiabing TONG ; Zegeng LI ; Mingxiang HAN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(10):160-163
This article systematically summarized the clinical experience of Professor Han Mingxiang,a national TCM master,in treating chronic obstructive pulmonary disease(COPD)from the perspective of the"qi monism"theory,proposing an innovative"three stages,three strategies"diagnostic and treatment approach.Under the guidance of"qi monism",Professor Han believes that the core pathological mechanisms of COPD progress are through three successive stages:dysfunction in the ascent and descent of qi,deficiency of yang qi,and prolapse of the great qi,all of which stem from the disruption of the dynamic balance of qi.In response to this chain of qi imbalance,Professor Han develops three strategies:"strengthening the foundation","illuminating the central yang",and"lifting and correcting",which aim to regulate qi flow,support yang qi,and coordinate the three energizers in a phased manner.This approach seeks to achieve dynamic restoration and holistic balance of qi,with prescriptions carefully aligned with the dynamic balance and pathological changes of qi,yielding distinctive therapeutic effects.
9.Correlation between cognitive impairment and depression in elderly patients with type 2 diabetes mellitus
Yuanyuan ZHAN ; Xinyue XU ; Bowen LU ; Muxin ZHANG ; Fangbo CHEN ; Jie FENG ; Qingrong PAN ; Zhe CHEN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(4):426-430
Objective To investigate the correlation between cognitive impairment and depression in elderly patients with type 2 diabetes mellitus(T2DM).Methods Based on China Health and Retirement Longitudinal Study in 2011,totally 521 elderly T2DM patients were enrolled,and according to the results of minimum mental state examination(MMSE)and their education lev-els,they were divided into a cognitively impaired group(437 cases)and a cognitively normal group(84 cases).Center for ED Epidemiological Survey Depression Scale was used to assess the depression symptoms.The correlation between cognitive impairment and depression was analyzed.Results Compared with the cognitively normal group,the cognitively impaired group had signifi-cantly advanced age(71.98±5.29 year vs 69.42±3.98 year,P=0.000),larger proportion of de-pression(60.6%vs 35.7%,P=0.000),and higher C-reactive protein level(5.09±12.80 mg/L vs 2.25±2.43 mg/L,P=0.000),and obviously lower ratios of being married(72.1%vs 86.9%,P=0.001)and having cardiovascular disease(20.1%vs 32.1%,P=0.010),and decreased estimated glomerular filtration rate[77.15±15.88 ml/(min·1.73 m2)vs 81.91±13.55 ml/(min·1.73 m2),P=0.001].Multivariate logistic regression analysis showed that cognitive impairment was an independent risk factor for the development of depression in elderly T2DM patients(OR=3.44,95%CI:1.89-6.27,P<0.01).ROC curve analysis indicated that the AUC value of MMSE score in predicting depression in elderly T2DM patients was 0.669(95%CI:0.626-0.709,P<0.01).The direct effect of cognitive impairment and the mediating effect of loneliness on depression in elderly T2DM patients accounted for 72.22%and 27.78%of the total effect,respectively.Conclu-sion Cognitive impairment is associated with the presence of depression in elderly T2DM pa-tients,and loneliness plays a mediating role.
10.Combining proprioceptive training with core stability training improves the balance and lower limb motor functioning of burns patients
Haiyang ZHAO ; Juntao HAN ; Jiaqi LIU ; Dahai HU ; Qin ZHOU ; Chan ZHU ; Jin XU ; Bowen ZHANG ; Zongshi QI
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(5):425-429
Objective:To observe any influence of combining proprioceptive training with core stability training in rehabilitation motor functioning and balance after extensive burns.Methods:Sixty patients with lower limb motor and balance disorders after extensive burns were randomly divided into a treatment group and a control group, each of 30. Both groups underwent skin grafting on the lower limbs. After the wounds had healed, both groups were given routine rehabilitation treatment, including joint stretching and muscle strength training, but the treatment group was additionally provided with proprioception and core stability training. Before and after 12 weeks of treatment, both groups′ lower limb motor function and walking ability were evaluated using the Fugl-Meyer Assessment (L-FMA), and static and dynamic balance were quantified using Holden Functional Ambulation Classification (FAC). The duration of standing on one leg with the eyes closed was recorded, along with Timed " Up & Go" Test (TUGT) times. After the treatment, each patient′s satisfaction was assessed using a self-designed questionnaire.Results:Significant improvement was observed in the average L- FMA and FAC scores after the treatment, as well as in the ability to stand on one leg with the eyes closed. The average TUGT time in both groups was shorter, but there had been significantly greater improvement of the treatment group than among the controls. Reported satisfaction was significantly higher among the treated group than among the controls.Conclusions:Supplementing basic rehabilitation with proprioception training and core stability training can further improve the motor functioning, balance and walking of persons who have suffered extensive burns.

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