1.Mechanisms and Strategy of Traditional Chinese Medicine in Treatment of Ischemic Stroke: A Review
Maodi WENG ; Qiuyan CHEN ; Kai WANG ; Yun LUO ; Xiaobo SUN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):310-316
Ischemic stroke (IS) represents a major global health challenge with complex pathological mechanisms. Although modern therapies such as intravenous thrombolysis and endovascular thrombectomy have advanced, their application remains constrained by narrow therapeutic time windows, hemorrhagic risks, and uneven distribution of medical resources. Traditional Chinese medicine (TCM) demonstrates unique value in the prevention and treatment of IS, owing to its multi-component, multi-target, and holistic regulatory characteristics. This review summarized the molecular mechanisms by which active ingredients and compound formulations of TCM exert therapeutic effects against IS through the regulation of inflammatory responses, oxidative stress, excitatory toxicity, apoptosis, and autophagy. Studies have indicated that components such as curcumin, baicalin, and astragaloside Ⅳ inhibit microglial activation and the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome to attenuate neuroinflammation, activate the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1 (HO-1) pathway to alleviate oxidative stress, modulate glutamate receptor function to counteract excitatory toxicity, and regulate the B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X protein (Bax), cysteine aspartate-specific protease (Caspase), and phosphatidylinositol 3 kinases (PI3K)/protein kinase B (Akt) signaling pathways to suppress neuronal apoptosis. Recent research has further revealed that TCM can modulate ferroptosis by targeting key proteins glutathione peroxidase 4 (GPX4) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) to maintain iron homeostasis, intervene in the "microbiota-gut-brain axis" to ameliorate dysbiosis and reduce neuroinflammation, utilize exosomes for brain-targeted drug delivery, and influence neural repair processes through epigenetic regulation. Furthermore, the review discussed the integrated mechanisms of compound formulations, such as Buyang Huanwu Decoction, in improving cerebral microcirculation and promoting neurovascular remodeling via multi-component synergy. It also analyzed the strategy and advantages of integrating TCM with Western medicine for IS treatment, providing a novel theoretical foundation and research directions for future investigations and clinical translation of TCM in IS management.
2.Analysis of data from the survey of radiotherapy resources in Gansu Province, China, 2024
Jialong WU ; Yun WANG ; Hanyu ZHANG ; Jie WANG ; Yanjun WANG ; Fang WANG ; Qian WANG ; Ruiying WANG ; Xiangru QU ; Limei NIU ; Qin CHEN
Chinese Journal of Radiological Health 2026;35(1):1-5
Objective To investigate the current distribution of radiotherapy resources in Gansu Province, evaluate the equity of resource allocation, and provide a scientific basis for optimizing regional resource allocation. Methods A questionnaire survey was carried out to assess radiotherapy resources in medical institutions across Gansu Province, China. The equity of radiotherapy resource distribution and associated disparities were assessed using the Gini coefficient, Lorenz curve, and Theil index. Results A total of 23 medical institutions in Gansu Province provided radiotherapy services, comprising 39 radiotherapy devices and 438 professionals, of whom medical physicists accounted for 16.9%. The radiotherapy frequency was 0.47 cases per thousand population. The Gini coefficients for radiotherapy resource distribution ranged from 0.38 to 0.56 by population and from 0.52 to 0.70 by geography. The Theil index for radiotherapy resources ranged from 1.36 to 3.67. Conclusion Radiotherapy resources in Gansu Province were insufficient, and the capacity of radiotherapy service was suboptimal. The equity of radiotherapy resource allocation by geography was worse than that by population. Therefore, it is imperative to address the shortage of radiotherapy resources, strengthen the professional workforce, enhance the capacity radiotherapy service and resource utilization, optimize resource allocation, and promote regional equity in radiotherapy provision in Gansu Province.
3.Prediction and verification of the mechanism of Chaiqi yigan granules improving hepatocellular carcinoma
Guiping MA ; Yuanjie ZHANG ; Yichi ZHOU ; Jinzhen LYU ; Conghui WANG ; Fenping LU ; Bowen LIU ; Yun RAN ; Shiping HU
China Pharmacy 2026;37(5):620-625
OBJECTIVE To predict and validate the mechanisms of Chaiqi yigan granules (CQYG) improving hepatocellular carcinoma (HCC). METHODS The signaling pathways of CQYG intervention in HCC were predicted using network pharmacology. A mice model of transplanted hepatocellular carcinoma was established by injecting H22 hepatoma cells into the axilla. Successfully modeled mice were randomly divided into model group (normal saline), sorafenib group (positive control, 50 mg/kg), and CQYG low-, medium- and high-dose groups (24.83, 49.66, 99.32 g/kg), with 10 mice in each group. Mice in each group were administered the corresponding drug solution or normal saline intragastrically, once a day, for 14 consecutive days. After last administration, pathological morphological changes in the tumor tissues of mice were observed in each group. Immunohistochemical staining was performed to detect the expression of the nuclear proliferation antigen Ki-67 in tumor tissues of mice. Western blot assay was used to measure the expression of proteins related to epithelial-mesenchymal transition (EMT) [N-cadherin, E-cadherin, Vimentin, matrix metalloproteinase 7 (MMP7)] and the mitogen-activated protein kinase (MAPK) signaling pathway [p38 MAPK, phosphorylated p38 MAPK, c-Jun N-terminal kinase (JNK), phosphorylated JNK, extracellular regulated protein kinase 1/2 (ERK1/2), phosphorylated ERK1/2] in tumor tissue of mice. RESULTS Network pharmacology analysis revealed that metabolic pathways, pathways in cancer, and the MAPK signaling pathway were key signaling pathways through which CQYG exert their anti-hepatocellular carcinoma effects. In animal experiments, the tumor tissues of mice in the model group exhibited dense tumor cells and vigorous growth. Compared with model group, CQYG high-dose group showed a decreased density of tumor cells in the tumor tissues of mice. Moreover, the expression levels of Ki-67, N-cadherin, MMP7 and Vimentin proteins, along with the phosphorylation levels of ERK1/2 and JNK proteins, were all significantly reduced ( P <0.05). The expression level of E-cadherin protein was significantly increased ( P <0.05), the phosphorylation level of p38 MAPK protein was increased, the difference was not statistically significant ( P >0.05). CONCLUSIONS CQYG can inhibit EMT by regulating the MAPK signaling pathway, thereby suppressing tumor cell invasion and metastasis and ultimately exerting a therapeutic effect in improving HCC.
4.Relationship of screen time and sleep duration with screening myopia among junior and senior high school students
CHEN Xinyi, WANG Yun, ZENG Xia
Chinese Journal of School Health 2026;47(3):430-433
Objective:
To explore the relationship of screen time and sleep duration with screening myopia among junior and senior high school students, so as to provide evidence for the prevention and control of myopia among students.
Methods:
From March to October 2024, 429 junior and senior high school students from a district of Guangzhou were selected using stratified cluster random sampling method. Standardized logarithmic visual acuity chart was used for vision assessment, while Questionnaire for the Physical Health Monitoring System of Students in Guangzhou was employed to collect students screen time and sleep duration. The Chi square test was used to compare differences across different groups, and binary Logistic regression analysis was employed to analyze the association of screen time and sleep duration with screening myopia.
Results:
The overall prevalence of screening myopia was 79.5%, with significant differences across educational stage, sex, screen time and sleep duration groups( χ 2=41.64, 9.75, 23.89 , 8.17, all P <0.05).Binary Logistic regression analysis revealed that, compared to the high screen time & insufficient sleep group, the low screen & sufficient sleep group ( OR=0.25, 95%CI =0.09-0.68), the low screen & insufficient sleep group ( OR= 0.27 , 95%CI =0.13-0.56), and the high screen & sufficient sleep group ( OR=0.26, 95%CI =0.10-0.70) exhibited significantly lower screening myopia risks (all P <0.05). After adjusting for sex and educational stage, low screen time & insufficient sleep was significantly associated with screening myopia ( OR=0.48, 95%CI =0.23-0.98); the multiplicative interaction term was statistically significant ( OR=0.99,95%CI =0.98-1.00)(both P <0.05).
Conclusion
The interaction effect between screen time and sleep duration in relation to screening myopia suggests a need to focus on daily routines and screen use habits among junior and senior high school students for ensuring sufficient sleep and limiting screen exposure.
5.Analyses of the epidemiological characteristics of multiple pathogens in people aged 14 years and above with acute respiratory infection in Huangpu District of Shanghai from 2015 to 2024
Yun ZHANG ; Yinzi CHEN ; Zhenzi ZUO ; Yu WANG ; Fujie SHEN ; Yuliang HUANG ; Qiang GAO ; Chenyan JIANG ; Yijun WANG
Shanghai Journal of Preventive Medicine 2026;38(2):116-121
ObjectiveTo analyze the epidemiological characteristics of 8 major respiratory pathogens in influenza-like illness (ILI) cases with acute respiratory infections at fever clinics in Huangpu District, Shanghai from 2015 to 2024, and to provide a scientific basis for the prevention and treatment of respiratory diseases. MethodsA retrospective study was conducted in Huangpu District. Individuals meeting the case definition of ILI from 2015 to 2024 was registered. Their nasopharyngeal swabs were collected for pathogen detection. A total of 8 respiratory viruses were tested, including Influenza A virus (Flu A), Influenza B virus (Flu B), adenovirus (ADV), enterovirus/human rhinovirus (EV/HRV), human parainfluenza virus (HPIV), human coronavirus (HCoV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV). ResultsFrom 2015 to 2019, a total of 344 ILI cases were tested, of which 192 out of 344 cases (55.81%) were tested positive for single respiratory pathogen. From 2023 to 2024, 1 557 ILI cases were tested, with 572 out of 1 557 cases (36.74%) being positive for single pathogen. From 2023 to 2024, the positive rate of single pathogen in ILI cases was significantly lower than that in 2015‒2019 (χ2=42.66, P<0.001). Specifically, the positive rate of Flu A (χ2=74.43, P<0.001) decreased, while that of HPIV (χ2=8.66, P=0.003) increased, both with statistically significant differences. According to the seasonal pattern, the epidemic intensity of Flu A decreased in summer, while that of HPIV increased in summer and autumn. Demographic results showed statistically significant differences in the positive rates of EV/HRV between genders (χ2=22.38, P<0.001), with males exhibiting a higher positive rate than females. No statistically significant differences were identified in the positive rates of single pathogen among different age groups (χ2=4.42, P=0.110). Nevertheless, statistically significant differences were noted when comparing the positive rates of EV/HRV, Flu A, Flu B and HPIV across different age groups (P<0.05). EV/HRV was more commonly detected in the 15‒<25 age group (10.93%), while Flu A and HPIV had the highest positive rates in the ≥60 age group (21.24% and 4.77%). Flu B had the highest positive rate in the 25‒<60 age group (11.26%). 52.63% of cases with co-infections occurred during winter, with the primary pathogens involved being EV/HRV (9 cases) and HCoV (6 cases). The most prevalent combination of co-infection was Flu A with EV/HRV. ConclusionThe prevalence of respiratory pathogens among ILI cases from 2023 to 2024 exhibited notable fluctuations compared to that from 2015 to 2019. Therefore, influenza surveillance should be strengthened, and attention should also be paid to the prevalence of respiratory pathogens such as HPIV. These findings have profound implications for future research, surveillance, vaccine planning, and public health policy making.
6.Identification of risk factors for pneumoconiosis-related complications and development and application of an XGBoost-based early prediction model
Li ZHANG ; Peng PENG ; Yun WANG ; Dong LUO
Journal of Environmental and Occupational Medicine 2026;43(3):302-310
Background As one of the most severe occupational diseases in China, pneumoconiosis is significantly burdened by its complications, which adversely affects patients' quality of life. Objective To identify the influencing factors of complications in pneumoconiosis and to construct an early prediction model for pneumoconiosis complications, providing theoretical guidance for clinical diagnosis, treatment, and rehabilitation. Methods A case-control study was conducted using data from the Chongqing 5G Pneumoconiosis Rehabilitation Management Information Platform. A total of
7.Mechanism of Number 2 Feibi Recipe in Ameliorating Pulmonary Fibrosis in Mice by Modulating Endoplasmic Reticulum Stress in AT2 Cells to Attenuate Apoptosis and Promote Alveolar Repair
Yaodong CAI ; Jialing BEI ; Wan WEI ; Chengyan XU ; Yanli LIU ; Yong WANG ; Yang JIAO ; Yun CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):80-92
ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe (N2FBR) in idiopathic pulmonary fibrosis (IPF), focusing on its effects on endoplasmic reticulum (ER) stress, apoptosis, stemness maintenance, and regenerative capacity of alveolar type Ⅱ epithelial cells (AT2 cells), and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin (BLM). Mice were randomly divided into blank control, model, low-, and high-dose N2FBR intervention groups (9.1, 18.2 g·kg-1), and prednisolone intervention group (6.5 mg·kg-1). Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin (HE) and Masson's trichrome staining. Hydroxyproline (HYP) content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors, including collagen type Ⅰ alpha 1 chain (ColIa1), alpha-smooth muscle actin (α-SMA), and tissue inhibitor of metalloproteinase 1 (Timp1), were detected by real-time polymerase chain reaction (Real-time PCR). Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C (SPC) and cysteine-aspartic protease-3 (Caspase-3). Endoplasmic reticulum (ER) stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase (PERK). Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy (TEM). The expression levels of key proteins involved in ER stress and apoptosis pathways, including PERK, activating transcription factor 4 (ATF4), and Caspase-3, were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen (Ki-67) was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology (labeling AT2 cells with GFP) combined with Krt8 labeling was used to evaluate intermediate differentiation states, and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells (AT1) was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue, increased collagen deposition, elevated lung coefficient, decreased pulmonary function, and upregulation of fibrosis-related factors (P<0.01). High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction, significantly reduced HYP content (P<0.01), and significantly downregulated ColIa1, α-SMA, and Timp1 expression (P<0.01). Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group, which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group, which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group, which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4, as well as the apoptosis-related protein Caspase-3, were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group, which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells, the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group (P<0.01). Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive (Krt8⁺GFP⁺) cells increased in the model group, indicating differentiation arrest. This proportion was significantly reduced in the treatment group, and the morphology of GFP⁺ cells exhibited a flattened, extended shape, suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells, reduces AT2 cell apoptosis, restores lamellar body structure and function, enhances proliferation activity, and alleviates differentiation arrest to promote differentiation into AT1 cells, thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi, harmonizing Qi and blood, and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells, providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.
8.Clinical Efficacy of Gandou Fumu Decoction in Treating Hepatolenticular Degeneration with Liver Fibrosis of Liver-kidney Deficiency and Phlegm-blood Stasis Syndrome
Pingping YANG ; Meixia WANG ; Changchang CAO ; Zhuang TAO ; Jiang DU ; Yun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):182-191
ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction (GDFMD) in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome, thereby providing evidence-based medical evidence for the treatment of Wilson's disease (WD)-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1, 2023, to October 1, 2024. Participants were divided into a control group and an observation group, with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate (DMPS). On this basis, the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days, for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses, respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement (LSM), liver serological markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅳ collagen (C-Ⅳ), laminin (LN), N-terminal propeptide of type Ⅲ procollagen (PⅢNP), and hyaluronic acid (HA)], fibrosis index based on 4 factors (FIB-4), AST to platelet ratio index (APRI), unified Wilson's disease rating scale part Ⅱ (UWDRS-Ⅱ), traditional Chinese medicine (TCM) syndrome score, 24-hour urinary copper, and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment, LSM levels decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses, and the improvement of LSM levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the levels of HA, LN, PⅢNP, and C-Ⅳ decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses, and the levels of HA, LN, and PⅢNP were more obvious (P<0.05). After four treatment courses in the observation group, the levels of HA, LN, PⅢNP, and C-Ⅳ were improved more significantly (P<0.05). Compared with those before treatment, ALT and AST levels decreased in both groups after two and four treatment courses (P<0.05). Compared with the control group after treatment, there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses, and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, APRI score and FIB-4 index level decreased in both groups after two and four treatment courses (P<0.05). Compared with those in control group after treatment, there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses, and the APRI score in the observation group was more obvious after four treatment courses (P<0.05), with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment, the levels of TCM syndrome scores decreased in both groups after two and four treatment courses (P<0.05). Compared with that of the control group after treatment, there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses, and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously, and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses (P<0.05). Compared with those of the control group after treatment, there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses, and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious (P<0.05). Compared with those before treatment, the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses (P<0.05). Compared with those in the control group after treatment, the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses (P<0.01). After two treatment courses, the 24-h urine copper level in the observation group showed a gradual decreasing trend, although it was higher than that before treatment. After four treatment courses, the control group had an improvement rate of 91.43%, an effective rate of 34.29%, and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%, an effective rate of 71.43%, and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group (P<0.05). Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy, and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety, which is worthy of clinical popularization and application.
9.Mechanism of Number 2 Feibi Recipe in Ameliorating Pulmonary Fibrosis in Mice by Modulating Endoplasmic Reticulum Stress in AT2 Cells to Attenuate Apoptosis and Promote Alveolar Repair
Yaodong CAI ; Jialing BEI ; Wan WEI ; Chengyan XU ; Yanli LIU ; Yong WANG ; Yang JIAO ; Yun CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):80-92
ObjectiveTo investigate the intervention mechanism of the traditional Chinese medicine Number 2 Feibi recipe (N2FBR) in idiopathic pulmonary fibrosis (IPF), focusing on its effects on endoplasmic reticulum (ER) stress, apoptosis, stemness maintenance, and regenerative capacity of alveolar type Ⅱ epithelial cells (AT2 cells), and to validate the modern translational pathway of the theory of "deficiency of Zong Qi leading to pulmonary atelectasis and atrophy". MethodsA mouse model of pulmonary fibrosis was induced by bleomycin (BLM). Mice were randomly divided into blank control, model, low-, and high-dose N2FBR intervention groups (9.1, 18.2 g·kg-1), and prednisolone intervention group (6.5 mg·kg-1). Pulmonary histopathological changes and collagen deposition were evaluated using hematoxylin-eosin (HE) and Masson's trichrome staining. Hydroxyproline (HYP) content was measured by the alkaline hydrolysis method. Lung coefficient and pulmonary function parameters were evaluated. The mRNA expression levels of fibrosis-related factors, including collagen type Ⅰ alpha 1 chain (ColIa1), alpha-smooth muscle actin (α-SMA), and tissue inhibitor of metalloproteinase 1 (Timp1), were detected by real-time polymerase chain reaction (Real-time PCR). Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Apoptosis of AT2 cells was further evaluated by double immunofluorescence staining for surfactant protein C (SPC) and cysteine-aspartic protease-3 (Caspase-3). Endoplasmic reticulum (ER) stress in AT2 cells was examined by double staining for SPC and protein kinase R-like endoplasmic reticulum kinase (PERK). Ultrastructural changes of ER and lamellar bodies in AT2 cells were observed by transmission electron microscopy (TEM). The expression levels of key proteins involved in ER stress and apoptosis pathways, including PERK, activating transcription factor 4 (ATF4), and Caspase-3, were detected by Western blot. Double immunofluorescence staining of SPC and Ki-67 antigen (Ki-67) was performed to evaluate the proliferative capacity of AT2 cells. Lineage tracing technology (labeling AT2 cells with GFP) combined with Krt8 labeling was used to evaluate intermediate differentiation states, and morphological transformation of AT2 cells into alveolar type Ⅰ epithelial cells (AT1) was observed. ResultsBLM-induced mice exhibited significant structural disruption of lung tissue, increased collagen deposition, elevated lung coefficient, decreased pulmonary function, and upregulation of fibrosis-related factors (P<0.01). High-dose N2FBR treatment significantly ameliorated lung tissue damage and dysfunction, significantly reduced HYP content (P<0.01), and significantly downregulated ColIa1, α-SMA, and Timp1 expression (P<0.01). Apoptosis analysis showed increased TUNEL-positive and Caspase-3-positive AT2 cells in the model group, which was significantly reduced by high-dose N2FBR treatment. TEM revealed swollen ER structures in AT2 cells of the model group, which tended to return to normal following treatment. PERK protein staining analysis showed evident ER stress in AT2 cells of the model group, which were markedly alleviated in the treatment group. The expression levels of ER stress-related proteins PERK and ATF4, as well as the apoptosis-related protein Caspase-3, were elevated in the model group and significantly reduced after treatment. TEM also revealed disrupted lamellar body structures in the model group, which tended to recover in the treatment group. Regarding the proliferative capacity of AT2 cells, the proportion of Ki-67⁺SPC⁺ AT2 cells significantly increased in the treatment group (P<0.01). Lineage tracing showed that the proportion of keratin 8-positive green fluorescent protein-positive (Krt8⁺GFP⁺) cells increased in the model group, indicating differentiation arrest. This proportion was significantly reduced in the treatment group, and the morphology of GFP⁺ cells exhibited a flattened, extended shape, suggesting restored differentiation toward AT1 cells. ConclusionN2FBR alleviates ER stress in AT2 cells, reduces AT2 cell apoptosis, restores lamellar body structure and function, enhances proliferation activity, and alleviates differentiation arrest to promote differentiation into AT1 cells, thereby repairing the alveolar epithelium and effectively blocking the progression of pulmonary fibrosis. Its traditional Chinese medicine mechanism of "replenishing Zong Qi, harmonizing Qi and blood, and unblocking pulmonary meridians" closely aligns with the modern regulatory pathway of AT2 stem cells, providing a novel theoretical basis and experimental evidence for the intervention of IPF with traditional Chinese medicine.
10.Clinical Efficacy of Gandou Fumu Decoction in Treating Hepatolenticular Degeneration with Liver Fibrosis of Liver-kidney Deficiency and Phlegm-blood Stasis Syndrome
Pingping YANG ; Meixia WANG ; Changchang CAO ; Zhuang TAO ; Jiang DU ; Yun XU ; Wenming YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):182-191
ObjectiveThis paper aims to evaluate the intervention effect of Gandou Fumu Decoction (GDFMD) in treating hepatolenticular degeneration with liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome, thereby providing evidence-based medical evidence for the treatment of Wilson's disease (WD)-related liver fibrosis with traditional Chinese medicine through clinical efficacy analysis. MethodsA total of 70 patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome meeting the inclusion criteria were enrolled from Anhui Provincial Hospital of TCM from October 1, 2023, to October 1, 2024. Participants were divided into a control group and an observation group, with 35 cases in each group. The control group received conventional copper chelation therapy with sodium dimercaptopropanesulfonate (DMPS). On this basis, the observation group was additionally administered GDFMD orally. Each treatment course lasted eight days, for a total of four treatment courses. Efficacy evaluations were performed before treatment and after the second and fourth treatment courses, respectively. The clinical efficacy and safety of GDFMD in the treatment of WD-related liver fibrosis were assessed by comparing the changes in liver stiffness measurement (LSM), liver serological markers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), type Ⅳ collagen (C-Ⅳ), laminin (LN), N-terminal propeptide of type Ⅲ procollagen (PⅢNP), and hyaluronic acid (HA)], fibrosis index based on 4 factors (FIB-4), AST to platelet ratio index (APRI), unified Wilson's disease rating scale part Ⅱ (UWDRS-Ⅱ), traditional Chinese medicine (TCM) syndrome score, 24-hour urinary copper, and safety indicators between the two groups before and after treatment. ResultsCompared with those before treatment, LSM levels decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of LSM levels in the observation group after two treatment courses, and the improvement of LSM levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the levels of HA, LN, PⅢNP, and C-Ⅳ decreased in both groups after two and four treatment courses (P<0.05). Compared with those after treatment, there was no statistically significant difference in the improvement of the C-Ⅳ levels in the observation group after two treatment courses, and the levels of HA, LN, and PⅢNP were more obvious (P<0.05). After four treatment courses in the observation group, the levels of HA, LN, PⅢNP, and C-Ⅳ were improved more significantly (P<0.05). Compared with those before treatment, ALT and AST levels decreased in both groups after two and four treatment courses (P<0.05). Compared with the control group after treatment, there was no statistically significant difference in the improvement of ALT and AST levels in the observation group after two treatment courses, and the improvement of ALT and AST levels in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, APRI score and FIB-4 index level decreased in both groups after two and four treatment courses (P<0.05). Compared with those in control group after treatment, there was no statistically significant difference in the improvement of APRI score and FIB-4 index level in the observation group after two treatment courses, and the APRI score in the observation group was more obvious after four treatment courses (P<0.05), with no statistically significant improvement in the FIB-4 index difference. Compared with those before treatment, the levels of TCM syndrome scores decreased in both groups after two and four treatment courses (P<0.05). Compared with that of the control group after treatment, there was no statistically significant difference in the improvement of the level of TCM syndrome scores in the observation group after two treatment courses, and the improvement of the level of TCM syndrome scores in the observation group was more obvious after four treatment courses (P<0.05). Compared with those before treatment, the UWDRS-Ⅱ scores in both groups after two treatment courses were not improved obviously, and the UWDRS-Ⅱ scores in both groups decreased after four treatment courses (P<0.05). Compared with those of the control group after treatment, there was no statistically significant difference in the improvement of the UWDRS-Ⅱ scores in the observation group after two treatment courses, and the improvement of the UWDRS-Ⅱ scores in the observation group after four treatment courses was more obvious (P<0.05). Compared with those before treatment, the 24-h urine copper levels were significantly higher in both groups after two and four treatment courses (P<0.05). Compared with those in the control group after treatment, the 24-h urine copper levels in the observation group were significantly higher after two and four treatment courses (P<0.01). After two treatment courses, the 24-h urine copper level in the observation group showed a gradual decreasing trend, although it was higher than that before treatment. After four treatment courses, the control group had an improvement rate of 91.43%, an effective rate of 34.29%, and an apparent rate of 2.86%. The observation group had an improvement rate of 94.29%, an effective rate of 71.43%, and an apparent rate of 8.57%. The efficacy of the observation group was better than that of the control group (P<0.05). Conclusion① The efficacy of GDFMD combined with DMPS therapy in patients with WD-related liver fibrosis of liver-kidney deficiency and phlegm-blood stasis syndrome is significantly better than that of single DMPS therapy, and the advantages of the combined therapy are more obvious with the prolongation of the treatment cycle. ② GDFMD combined with the DMPS therapy program in the long-term application exhibits no obvious adverse reactions with good safety, which is worthy of clinical popularization and application.


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