1.Zuoguiwan Mitigates Oxidative Stress in Rat Model of Hyperthyroidism Due to Kidney-Yin Deficiency via DRD4/NOX4 Pathway
Ling LIN ; Qianming LIANG ; Changsheng DENG ; Li RU ; Zhiyong XU ; Chao LI ; Mingshun SHEN ; Yueming YUAN ; Muzi LI ; Lei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):43-51
ObjectiveTo decipher the mechanism by which Zuoguiwan (ZGW) treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 (DRD4)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone (0.35 mg·kg-1). After successful modeling, the rats were randomized into model, methimazole (positive control, 5 mg·kg-1), low-, medium-, and high-dose (1.85, 3.70, 7.40 g·kg-1, respectively) ZGW, and normal control groups. After 21 days of continuous gavage, the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones [triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH)], renal function indexes [serum creatine (Scr) and blood urea nitrogen (BUN)], energy metabolism markers [cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)], and oxidative stress-related factors [superoxide dismutase (SOD), malondialdehyde (MDA), and NADPH)] were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was employed to analyze the expression of DRD4, NOX4, mitochondrial respiratory chain complex proteins [NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) and cytochrome C oxidase subunit 4 (COX4)], and inflammation-related protein [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), p38 mitogen-activated protein kinase (MAPK)] pathway in the renal tissue. ResultsCompared with the normal group, the model group showed mental malaise, body weight decreases (P<0.01), inflammatory cell infiltration in the renal tissue, a few residual parotid glands in the thyroid, elevations in serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA, and NADPH (P<0.01), down-regulation in protein levels of TSH, SOD, and DRD4 (P<0.05, P<0.01), and up-regulation in expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.01). Compared with the model group, ZGW increased the body weight (P<0.05, P<0.01), reduced the infiltration of renal interstitial inflammatory cells, restored the thyroid structure and follicle size, lowered the serum levels of T3, T4, Scr, BUN, cAMP, cAMP/cGMP, MDA and NADPH (P<0.05, P<0.01), up-regulated the expression of TSH, SOD and DRD4 (P<0.05, P<0.01), and down-regulated the expression of NOX4, p-p38 MAPK/p38 MAPK, and inflammatory factors (P<0.05, P<0.01). Moreover, high-dose ZGW outperformed methimazole (P<0.05). ConclusionBy activating DRD4, ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway, reduce oxidative stress and inflammatory response, thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.
2.Effect of Feiyanning Granules on Inducing Ferroptosis in Lung Cancer Cells and Its Regulatory Function onNrf2/SLC7A11/GPX4 Signaling Pathway
Xin LIU ; Wenjie WANG ; Zhenye XU ; Zhan ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):100-107
ObjectiveThis study aims to explore the effect of Feiyanning granules on ferroptosis in lung cancer cells and its regulatory function within the nuclear transcription factor E2-related factor 2 (Nrf2)/mouse solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. MethodsThe cell counting kit-8 (CCK-8) method was used to detect the effect of Feiyanning granule on the proliferation of A549 lung cancer cells. A549 lung cancer cells were categorized into a blank group, a ferroptosis inhibitor-1 (Fer-1) group (10 μmol·L-1), a Feiyanning granules (600 mg·L-1) group, and a Feiyanning granules + Fer-1 group. After 48 hours of intervention, the activity and morphology of the cells were observed. The CCK-8 method was employed to measure cell viability. Biochemical assays were carried out to measure the levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and ferrous ions (Fe²⁺) in A549 cells. Western blot was utilized to evaluate the expression levels of Kelch-like ECH-associated protein 1 (Keap1), Nrf2, SLC7A11, and GPX4 proteins. A549 lung cancer cells were categorized into a blank group and a Feiyanning Granule group (600 mg·L-1), and mitochondrial morphology was examined via transmission electron microscopy (TEM). ResultsAfter the intervention of Feiyaning granules, the proliferation of A549 cells was significantly inhibited in a concentration-dependent manner compared with that in the blank group (P<0.01). Compared with the blank group, the Feiyanning granules group exerted an significantly inhibitory effect on the viability of lung cancer cells (P<0.01). Compared with that in the Feiyanning granules group, the cell viability in the Feiyanning granules +Fer-1 group was obviously restored (P<0.05). Compared with the blank group, the Feiyanning Granule group showed a significant increase in the levels of ROS, MDA, and Fe²⁺ (P<0.01), a significant decrease in the GSH level (P<0.01), and facilitated ferroptosis. Compared with the blank group, the Feiyanning granules group showed significantly decreased expression of Nrf2, SLC7A11, and GPX4 proteins and enhanced expression of Keap1 (P<0.01). Compared with those in the Feiyanning Granule group, the protein levels of Nrf2, SLC7A11, and GPX4 increased significantly (P<0.01), and the expression of Keap1 decreased significantly in the Feiyanning granules + Fer-1 group (P<0.01). Compared with the blank group, the Feiyaning granules group exhibited reduced mitochondrial size and increased matrix electron density. ConclusionFeiyanning granules can induce ferroptosis in lung cancer cells, and its underlying mechanism might be associated with the inhibition of the Nrf2/SLC7A11/GPX4 signaling pathway.
3.Clinical Efficacy and Mechanism of Bupi Qingfei Prescription in Treating Stable Bronchiectasis
Zi YANG ; Guangsen LI ; Bing WANG ; Bo XU ; Jianxin WANG ; Sheng CAO ; Xinyan CHEN ; Xia SHI ; Qing MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):162-169
ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription (BPQF) in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized, double-blind, placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control (PC) groups. On the basis of conventional Western medicine treatment, the BPQF granules and placebo were respectively administered at 10 g each time, twice a day, for a course of 24 weeks. The TCM symptom scores, Quality of Life Questionnaire for Bronchiectasis (QOL-B) scores, lung function indicators, T lymphocyte subsets, level of inflammatory factors in the sputum, level of neutrophil elastase (NE) in the sputum, and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study, encompassing 32 in the BPQF group and 32 in the PC group. After treatment, the BPQF group showed decreased TCM symptom scores (P<0.01), increased QOL-B scores (P<0.01), and declined levels of tumor necrosis factor (TNF)-α and NE (P<0.05, P<0.01). The PC group showed decreased TCM symptom (except spleen deficiency) scores (P<0.01), increased the QOL-B health cognition and respiratory symptom domain scores (P<0.05, P<0.01), and a declined TNF-α level (P<0.01). Moreover, the BPQF group had lower TCM symptom (except chest tightness) scores (P<0.05, P<0.01), higher QOL-B (except treatment burden) scores (P<0.05, P<0.01), and lower levels of interleukin-6 and TNF-α (P<0.05) than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.
4.Exploring Chemical Constituent Distribution in Blood/Brain(Hippocampus) and Emotional Regulatory Effect of Raw and Vinegar-processed Products of Citri Reticulatae Pericarpium Viride
Yi BAO ; Yonggui SONG ; Qianmin LI ; Zhifu AI ; Genhua ZHU ; Ming YANG ; Huanhua XU ; Qin ZHENG ; Yiting HUANG ; Zihan GAO ; Dan SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):189-197
ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride(CRPV), and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts, as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards, databases, and relevant literature were utilized for compound annotation, with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups, including the blank group, model group, diazepam group(2.5 mg·kg-1), raw CRPV low/high dose groups(0.6, 1.2 g·kg-1), and vinegar-processed CRPV low/high dose groups(0.6, 1.2 g·kg-1), with 10 mice per group. Except for the blank group, all other groups underwent chronic restraint stress(2 h·d-1) for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling, with a total treatment duration of 10 d. Following model-based drug administration, mice underwent open-field, forced swimming, and elevated plus maze tests. After anesthesia with isoflurane, whole brains were collected from each group of mice, and hippocampi were dissected. Reactive oxygen species(ROS) level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei(NeuN) and peroxisome proliferator-activated receptor alpha(PPARα) expressions in hippocampal tissue. Then, pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders, exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV, with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds, including 20 flavonoids, 20 flavonoid glycosides, 3 triterpenes, 3 phenolic acids, 1 alkaloid, and 6 other compounds. Twenty-one components were detected in blood(15 methoxyflavones, 4 flavonoid glycosides, and 2 phenolic acids), with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues(all common to both forms). In regulating emotional disorders, Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology, particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS(P<0.05). ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing, but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway, thereby negatively regulating ROS generation in the hippocampus, reducing oxidative stress, and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards, pharmacodynamic material research, and active drug development of raw and vinegar-processed CRPV.
5.Identification and Biological Characterization of Pathogen and Screening of Effective Fungicides for Wilt of Tetradium ruticarpum
Yuxin LIU ; Qin XU ; Yue YUAN ; Tiantian GUO ; Zheng'en XIAO ; Shaotian ZHANG ; Ming LIU ; Fuqiang YIN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):198-206
ObjectiveTo identify the pathogen species responsible for the wilt disease of Tetradium ruticarpum in Chongqing, investigate there biological characteristics, and screen effective fungicides, so as to provide a theoretical basis for disease control in production. MethodsThe pathogen was isolated via the tissue culture method. Pathogenicity was verified according to Koch's postulates. The pathogen was identified based on morphological characteristics and multi-gene phylogenetic analysis. The mycelial growth rate method was used for biological characterization of the pathogen and fungicide screening. ResultsThe pathogen colonies were nearly circular with irregular edges, white, short, velvety aerial hyphae, and pale purple undersides. Macroconidia were colorless, sickle-shaped, with 3-5 septa, while microconidia were transparent, elliptical, aseptate or with 1-2 septa. Multi-gene phylogenetic analysis showed that the pathogen clustered in the same clade as Fusarium fujikuroi with 100% support, which, combined with morphological characteristics, identified the pathogen causing wilt of T. ruticarpum in Chongqing as F. fujikuroi. The optimal conditions for the mycelial growth of F. fujikuroi were mung bean agar (MBA) with glucose as the carbon source, beef extract and yeast powder as nitrogen sources, 28 ℃, pH 7.0, and alternating light/dark conditions. The optimal conditions for sporulation were potato dextrose agar (PDA) with glucose as the carbon source, beef extract as the nitrogen source, 28 ℃, pH 7.0, and complete darkness. Among chemical fungicides, phenazine-1-carboxylic acid exhibited the strongest inhibitory effect on F. fujikuroi. Shenqinmycin and tetramycin were the most effective bio-fungicides. ConclusionThis study is the first to report F. fujikuroi as the causal agent of wilt disease in T. rutaecarpa. The chemical fungicide phenazine-1-carboxylic acid and the bio-fungicides shenqinmycin and tetramycin showed strong inhibitory effects against F. fujikuroi.
6.New advances in etiological diagnosis, prevention, and treatment of infectious keratopathy
International Eye Science 2026;26(1):39-44
Infectious keratitis(IK)is a major blinding eye disease worldwide. Early diagnosis and treatment are crucial for improving prognosis and reducing the economic burden. This article reviews advances in the diagnosis and treatment of IK, aiming to provide new insights for clinical management. In terms of diagnosis, in addition to conventional methods such as microbial culture and confocal microscopy, molecular diagnostic technologies—including high-throughput sequencing(NGS), CRISPR, and nanotechnology-based systems—have significantly enhanced the sensitivity and specificity of multiplex pathogen detection. These approaches are particularly valuable for identifying mixed infections and rare pathogens. Regarding treatment, in response to the growing challenge of drug resistance, novel drug delivery systems employing nanotechnology and bioactive dressings have markedly improved antibacterial efficacy by enhancing drug penetration and retention. Immunomodulatory therapy and photodynamic therapy effectively control inflammatory responses and improve outcomes. Integrated traditional Chinese and Western medicine, as well as microbiome-based therapies, have demonstrated significant advantages in reducing recurrence rates. Stem cell therapy offers new hope for repairing severe corneal damage, while gene therapy—through gene editing or transduction—strengthens the innate defense mechanisms of the cornea and reduces treatment-related side effects.
7.Current strategies and future directions in the treatment of age-related macular degeneration
Jian XU ; Jie WANG ; Haixin FU ; Chaopeng LI
International Eye Science 2026;26(1):56-62
Age-related macular degeneration(ARMD)is a progressive visual impairment fundus disease that frequently occurs in individuals aged >55 years. The main risk factors are aging, long-term smoking, genetics, and racial differences. Pathogenesis includes abnormal function of the retinal pigment epithelium, damaged blood-retinal barrier, and abnormal immune function. Currently, intravitreal injection(IVI)of anti-vascular endothelial growth factor(VEGF)drugs is the preferred treatment option for ARMD in clinical practice. However, it also faces challenges such as repeated treatments, high medical costs, and poor patient compliance. The predicament in the treatment of ARMD has given rise to several new treatment options. This article aims to review the treatment methods and progress of dry ARMD and wet ARMD, providing new ideas for addressing the limitations of the current clinical anti-VEGF treatment.
8.Correlation of serum levels of leukocyte-derived chemotaxin 2 and complement C1q/tumor necrosis factor-related protein 5 with diabetic retinopathy
International Eye Science 2026;26(1):109-113
AIM: To investigate the correlation of serum leukocyte-derived chemotaxin 2(LECT2)and complement C1q/tumor necrosis factor-related protein 5(CTRP5)with diabetic retinopathy(DR).METHODS:A single-center cross-sectional analysis was conducted on 138 patients with type 2 diabetes mellitus(T2DM)admitted to our hospital from April 2023 to April 2025. According to the diagnostic results, they were divided into a non-DR group(60 cases)and a DR group(78 cases). The DR group was further divided into a proliferative DR(PDR)group(29 cases)and a non-proliferative DR(NPDR)group(49 cases). Pearson correlation analysis was used to assess the correlation of LECT2 and CTRP5 with glucose-lipid metabolism indicators. Logistic regression analysis was conducted to identify the influencing factors for the occurrence of DR in T2DM patients. ROC curve analysis was performed to evaluate the diagnostic value of serum LECT2 and CTRP5 for DR in T2DM patients.RESULTS: A comparison of general patient data between the two groups showed no significant differences. The DR group had higher serum levels of LECT2, CTRP5, total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and homeostatic model assessment of insulin resistance(HOMA-IR)than the non-DR group, while high-density lipoprotein cholesterol(HDL-C)was lower(all P<0.05). The serum levels of LECT2 and CTRP5 in the PDR group were higher than those in the NPDR group(all P<0.05). Serum LECT2 and CTRP5 positively correlated with TC, TG, LDL-C, and HOMA-IR, and negatively correlated with HDL-C(all P<0.001). Logistic results showed that duration of diabetes, TC, TG, LDL-C, HOMA-IR, LECT2, and CTRP5 were risk factors for DR occurrence in T2DM patients(all P<0.05). The ROC curve showed that the AUCs for serum LECT2, CTRP5 alone, and combined in diagnosing DR in T2DM patients were 0.830, 0.839, and 0.915, respectively. The AUC for the combined diagnosis was higher than that of LECT2 or CTRP5 alone according to the DeLong test(Z=2.818, 2.824, P=0.015, 0.012).CONCLUSION:Serum LECT2 and CTRP5 levels are closely related to the development of DR in T2DM patients, and joint detection has certain clinical value in diagnosing DR in T2DM patients.
9.Early predictive value of pre-treatment tear inflammatory factor levels in patients with dry eye
Yingxing JIANG ; Yuqiu XU ; Yunyun YANG ; Yu ZHANG
International Eye Science 2026;26(1):157-162
AIM: To investigate the application value of pre-treatment tear inflammatory factor levels in predicting therapeutic efficacy for dry eye patients.METHODS:Prospective controlled observational study. A total of 120 patients with dry eye(240 eyes)admitted to our hospital from November 2022 to March 2024 were included. Before dry eye treatment, the levels of inflammatory factors, including interlukin-4(IL-4), IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IL-18, IL-1β, interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α), granulocyte-colony stimulating factor(G-CSF), granulocyte-macrophage colony-stimulating factor(GM-CSF), monocyte chemoattractant protein-1(MCP-1)in the tear fluid were detected by ELISA. According to the treatment protocol in the Chinese Expert Consensus on the Treatment of Dry Eye(2020), the patients were given treatments, and the related factors affecting the treatment outcomes of dry eye patients were analyzed.RESULTS:After continuous treatment for 4 wk, all the patients completed follow-up, and they were divided into the markedly effective group(60 patients, 120 eyes)and the ineffective group(60 patients, 120 eyes)based on their therapeutic effects. The markedly effective group had significantly lower pre-treatment levels of IL-6, IL-10, IL-18, IL-1β, and TNF-α than the poor efficacy group(all P<0.05). IL-6(OR=0.994), IL-18(OR=0.998), IL-1β(OR=0.933), and TNF-α(OR=0.998)were independently associated with treatment efficacy(all P<0.05). The nomogram model yielded a C-index of 0.971(95% CI: 0.950-0.993), with calibration curves closely aligned to the ideal curve. The model demonstrated significant predictive value for early therapeutic efficacy(sensitivity=96.67%, specificity=71.67%, cutoff=208, AUC=0.866, 95% CI=0.794-0.952, P<0.001).CONCLUSION:The nomogram model constructed based on the levels of inflammatory factors in dry eye patients before treatment can well predict the treatment effect of patients.
10.Therapeutic Mechanisms of Xiebai San on Lung Heat-induced Cough and Asthma via Modulating Lung-Brain Axis Metabolism Based on Spatial Metabolomics
Yue XU ; Fuzhi MA ; Yeerjiang AYIMAN ; Lin ZHU ; Qingce ZANG ; Zhijie MA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):41-48
ObjectiveBased on whole-animal mass spectrometry imaging technology, spatial metabolomics was used to characterize in situ the metabolic alteration patterns in the lungs and brain of a rat model of lung heat-induced cough and asthma, as well as after treatment with Xiebai San. MethodsNine Sprague-Dawley (SD) rats were randomly divided into a blank group (physiological saline), a model group (physiological saline), and a Xiebai San group (9 g·kg-1), with three rats in each group. The model group and the Xiebai San group were both induced using lipopolysaccharide-ovalbumin (LPS-OVA) to establish an asthma rat model. After treatment with Xiebai San, the animals were euthanized on day 21 and rapidly frozen in liquid nitrogen to preserve morphology. Whole-animal tissue sections were prepared using a cryomicrotome, and imaging was performed using the Air-flow-assisted Desorption Electrospray Ionization Mass Spectrometry Imaging (AFADESI-MSI) platform. Based on the corresponding optical images, ion data of metabolites from the lung and brain tissues of each group were extracted. Differential metabolites were analyzed using SIMCA and GraphPad Prism 9.0 software. Metabolites were identified using the HMDB (

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