1.Influence of Wenfei Guyuan Umbilical Moxibustion on Quality of Life and Immune Function in Patients with Chronic Obstructive Pulmonary Disease in Stable Phase
Qionghua XIAO ; Yuanyuan MENG ; Gaoming WANG ; Minghang WANG ; Yong MENG ; Miao ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):241-250
ObjectiveThis paper aims to assess the effects of Wenfei Guyuan umbilical moxibustion on the quality of life and immune function in patients with chronic obstructive pulmonary disease (COPD) in stable phase. MethodsA multi-center randomized controlled trial design was employed,and the 220 cases of patients with COPD in stable phase from three grade A class-Ⅲ hospitals were included as research objects. The patients were randomly divided into the test group and control group,with each group consisting of 110 cases. Both groups received standardized treatment of western medicine,and the test group received Wenfei Guyuan umbilical moxibustion twice weekly for 13 weeks,followed by a 26-week follow-up period. Quality of life was evaluated by using the COPD assessment test (CAT),the modified COPD patient-reported outcomes (mCOPD-PRO) measure,and the modified effectiveness satisfaction questionnaire for COPD (mESQ-COPD) before treatment,four weeks, eight weeks, and 13 weeks of the treatment period,as well as 13 weeks and 26 weeks of the follow-up period. The number of acute exacerbation cases of patients in both groups was recorded during study period to evaluate the effect of Wenfei Guyuan umbilical moxibustion on acute exacerbations. 30 cases were randomly selected in both observation group and control group. Peripheral blood samples were collected before treatment and at 13 weeks of treatment. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of immunoglobulin A (IgA),immunoglobulin G (IgG),immunoglobulin M (IgM),interleukin 10 (IL-10),interleukin 17A (IL-17A),transforming growth factor β1 (TGF-β1),and tumor necrosis factor α (TNF-α). Flow cytometry was used to detect cluster of differentiation 4 positive (CD4+),cluster of differentiation 8 positive (CD8+),T helper 17 (Th17),and Treg levels, thereby preliminarily exploring the effect of Wenfei Guyuan umbilical moxibustion on immune function. ResultsA total of 220 patients were included,with five cases dropping out. 215 cases were finally included in the per-protocol set,including 107 in the treatment group and 108 in the control group. Baseline characteristics of the first two groups before treatment were compared between the two groups. In terms of life quality evaluation, the main effect of group differences on the CAT scores was significant (F=15.108,P<0.01). The main effects of group differences on the physical domain (F=38.807,P<0.01),psychological domain (F=38.996,P<0.01),environmental domain (F=17.436,P<0.01),and total score of mCOPD-PRO (F=41.972,P<0.01) were significant. The main effects of group difference on clinical symptoms domain of mESQ-COPD (F=81.516,P<0.01),work-life ability domain (F=36.549,P<0.001),environmental adaptation ability domain (F=22.677,P<0.01),therapeutic effect domain (F=74.055,P<0.01),and total score of mESQ-COPD (F=73.251,P<0.01) were significant. Regarding acute exacerbations,during the entire study period,as well as the treatment period and follow-up period,the observation group showed fewer patients experiencing acute exacerbations compared to the control group,but the difference between the two groups was not statistically significant. In terms of immune indicators,after 13 weeks of treatment,the levels of IgA,IgG,and IgM in the observation group were significantly better than those in the control group (P<0.05). The level of IL-10 was significantly higher than that in the control group (P<0.05),and the levels of IL-17A,TGF-β1,and TNF-α were significantly lower than those in the control group (P<0.05). Compared with those in the control group,the level of CD4+/CD8+ in the observation group was significantly increased (P<0.05),while the levels of CD4+ and Treg were slightly increased,but the difference was not statistically significant. The levels of CD8+,Th17,and Th17/Treg were significantly decreased (P<0.05). ConclusionWenfei Guyuan umbilical moxibustion can improve the quality of life, and immune function in patients with COPD in stable phase. It is worth promoting in clinical practice.
2.Research Progress on Tumor Microenvironment in Lung Cancer Spine Metastasis
Hongyang FU ; Yizhi LIU ; Yitong SHE ; Yaxin DU ; Ruixia WU ; Manglai LI ; Yong ZHU
Cancer Research on Prevention and Treatment 2026;53(2):158-164
The spine is the most common site of skeletal metastasis in lung cancer, which frequently leads to severe complications such as pathological fracture and neurological compromise and is associated with poor prognosis. The development and progression of spinal metastasis from lung cancer are linked to the unique local microenvironment and tumor microenvironment (TME) of the vertebral column. During metastatic evolution, the dense vascular network of the spine and a plethora of signaling molecules, together with the complex cellular constituents and their intricate interactions within the TME, all cooperate to facilitate the tumor invasion and colonization of the vertebral compartment. Mechanistic studies delineating the role of the TME in spinal metastasis from lung cancer have markedly expanded, fostering the emergence of innovative therapeutic strategies—including nanomedicines, sono-photodynamic therapy, gene therapy, and combination regimens. These strategies demonstrate remarkably potential for clinical translation and offer new directions for the precision management of spinal metastasis from lung cancer.
3.Qinlian Hongqutang Improves NASH by Promoting Macrophage Polarization Through TLR4 and STAT6 Signaling Pathways
Yong ZHANG ; Yong HU ; Yunliang HE ; Yang YANG ; Donghui CHEN ; Sijie DANG ; Jia HE ; Yaqi LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):10-20
ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang (QLHQT) on nonalcoholic steatohepatitis (NASH). MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling, mice were randomly assigned to the model group, low-, medium-, and high-dose QLHQT groups (0.51, 1.02, and 2.04 g·kg-1), and a positive control metformin group, with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), as well as hepatic TC, TG, and LDL-C contents, were determined by biochemical assays. Hematoxylin-eosin (HE) staining and oil red O staining were used to evaluate liver histopathology and lipid deposition, respectively. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Real-time polymerase chain reaction (Real-time PCR) were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group, body weight and serum and hepatic levels of TC, TG, and LDL-C were significantly increased in the model group (P<0.01). Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm, accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased, whereas the proportion of CD206-positive cells was markedly decreased (P<0.05). Hepatic inducible nitric oxide synthase (iNOS) levels and tumor necrosis factor-α (TNF-α) mRNA expression were significantly increased, while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased (P<0.01). The protein expression levels of Toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) in the liver were significantly increased (P<0.01). Compared with the model group, body weight was reduced in the high-, medium-, and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC, TG, and LDL-C levels were significantly decreased (P<0.01). Liver histopathology showed alleviated hepatic lipid deposition, with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased, whereas the proportions of CD206-positive cells were significantly increased in the high-, medium-, and low-dose QLHQT groups (P<0.05). Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased (P<0.01), whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased (P<0.01). The hepatic protein expression levels of TLR4, TRAF6, and MyD88 were significantly decreased, while signal transducer and activator of transcription 6 (STAT6) phosphorylation was significantly increased (P<0.05, P<0.01). There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice, and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.
4.Short-term efficacy of low-dose transscleral cyclophotocoagulation for persistent ocular hypertension in acute angle-closure glaucoma
Qiaoyun LI ; Yong JIA ; Baike ZHANG ; Xiaojing GUO ; Cong LU ; Xinli WEI ; Xuemin TIAN
International Eye Science 2026;26(4):706-710
AIM: To evaluate the safety and efficacy of low-dose transscleral cyclophotocoagulation(TSCP)in the management of persistent ocular hypertension after an acute attack of angle-closure glaucoma(AACG).METHODS:This retrospective study enrolled patients diagnosed with persistent ocular hypertension after an acute AACG attack at the No.988 Hospital of the Joint Logistics Support Force of the Chinese PLA between September 2023 and September 2024. All patients underwent low-dose TSCP using a semiconductor diode laser. Subsequent cataract surgery combined with goniosynechialysis was performed once intraocular pressure(IOP)was stabilized. Changes in anterior chamber depth(ACD), best-corrected visual acuity(VA), and IOP were compared before and after TSCP, as well as before and after phacoemulsification. Post-TSCP complications were also documented.RESULTS: A total of 21 patients(21 eyes)were enrolled, including 8 males and 13 females, with a mean age of 67.95±7.25 y. Compared with pre-cyclophotocoagulation values, ACD increased significantly at 3 d post-TSCP(1.49±0.18 vs 1.22±0.21 mm; P<0.001). BCVA and IOP decreased significantly at 1 d post-TSCP, pre-phacoemulsification, 1 wk post-phacoemulsification, and 1 mo post-phacoemulsification compared with pre-TSCP IOP(all P<0.01). Regarding postoperative complications, 2 eyes experienced pain on the day of the procedure, 5 eyes developed mild corneal endothelial folds, 2 eyes exhibited moderate anterior chamber inflammatory reaction, and 12 eyes showed shallow ciliary body detachment. No serious complications occurred during the 1-month follow-up period.CONCLUSION:Low-dose TSCP appears to be an effective bridging therapy for patients with persistent ocular hypertension following an AACG attack. It facilitates rapid IOP reduction, alleviates symptoms, and helps preserve visual function with a favorable safety profile, thereby reducing the risks associated with subsequent intraocular surgery.
5.Qinlian Hongqutang Improves NASH by Promoting Macrophage Polarization Through TLR4 and STAT6 Signaling Pathways
Yong ZHANG ; Yong HU ; Yunliang HE ; Yang YANG ; Donghui CHEN ; Sijie DANG ; Jia HE ; Yaqi LUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):10-20
ObjectiveTo investigate the therapeutic effects and mechanisms of Qinlian Hongqutang (QLHQT) on nonalcoholic steatohepatitis (NASH). MethodsC57BL/6J mice were randomly divided into normal and modeling groups. The NASH model was established by feeding a high-fat diet for 12 weeks. After successful modeling, mice were randomly assigned to the model group, low-, medium-, and high-dose QLHQT groups (0.51, 1.02, and 2.04 g·kg-1), and a positive control metformin group, with six mice in each group. The mice were treated for 8 weeks. Body weight was recorded before and after treatment. Serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), as well as hepatic TC, TG, and LDL-C contents, were determined by biochemical assays. Hematoxylin-eosin (HE) staining and oil red O staining were used to evaluate liver histopathology and lipid deposition, respectively. Flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Real-time polymerase chain reaction (Real-time PCR) were used to assess hepatic macrophage expression and related markers. Western blot and immunofluorescence were used to investigate the potential mechanisms of QLHQT in regulating macrophage polarization. ResultsCompared with the normal group, body weight and serum and hepatic levels of TC, TG, and LDL-C were significantly increased in the model group (P<0.01). Liver histopathology showed unevenly distributed round lipid droplets in the hepatocyte cytoplasm, accompanied by inflammatory cell aggregation. Flow cytometry showed that the proportion of CD86-positive cells was significantly increased, whereas the proportion of CD206-positive cells was markedly decreased (P<0.05). Hepatic inducible nitric oxide synthase (iNOS) levels and tumor necrosis factor-α (TNF-α) mRNA expression were significantly increased, while hepatic IL-10 levels and IL-4 mRNA expression were significantly decreased (P<0.01). The protein expression levels of Toll-like receptor 4 (TLR4), tumor necrosis factor receptor-associated factor 6 (TRAF6), and myeloid differentiation factor 88 (MyD88) in the liver were significantly increased (P<0.01). Compared with the model group, body weight was reduced in the high-, medium-, and low-dose QLHQT groups and in the metformin group. Serum and hepatic TC, TG, and LDL-C levels were significantly decreased (P<0.01). Liver histopathology showed alleviated hepatic lipid deposition, with markedly reduced lipid droplets and inflammation. Immunofluorescence and flow cytometry showed that the proportions of CD86-positive cells were significantly decreased, whereas the proportions of CD206-positive cells were significantly increased in the high-, medium-, and low-dose QLHQT groups (P<0.05). Hepatic iNOS levels and TNF-α mRNA expression were significantly decreased (P<0.01), whereas hepatic IL-10 levels and IL-4 mRNA expression were significantly increased (P<0.01). The hepatic protein expression levels of TLR4, TRAF6, and MyD88 were significantly decreased, while signal transducer and activator of transcription 6 (STAT6) phosphorylation was significantly increased (P<0.05, P<0.01). There was no statistically significant difference in total STAT6 protein expression. ConclusionQLHQT effectively ameliorates hepatic inflammation in NASH mice, and the mechanism may involve STAT6- and TLR4-mediated signaling pathways driving polarization of M1 macrophages toward the M2 phenotype.
6.Analysis of knowledge related to human papillomavirus and vaccination willingness among college students in Guizhou Province
REN Li, WU Yuqian, ZHU Liwan,LI Fenxiang, FAN Shujun, GAN Jianzhe, DONG Shuwen, LU Yong
Chinese Journal of School Health 2026;47(2):212-216
Objective:
To explore human papillomavirus (HPV) and vaccination related knowledge and vaccination willingness of college students in Guizhou Province and their related factors, so as to provide a basis for formulating targeted intervention strategies.
Methods:
From May to June 2025, by applying convenience sampling method,4 567 college students were selected from 8 universities in Guizhou Province to conduct a questionnaire survey. Awareness of HPV and vaccination related knowledge, vaccination willingness as well as related factors among college students were also analyzed. The t test and Chi square test were used for comparison between groups, and multifactor Logistic regression was employed to analyze the related factors of HPV vaccination willingness among college students.
Results:
The HPV and vaccine knowledge score of college students in Guizhou Province was ( 10.50 ±2.09), and the score of girls (10.81±1.82) was higher than that of boys (10.19±2.30) ( t=10.09, P <0.01). The HPV vaccination willingness rate of college students was 65.6%, and the rate was higher in girls than in boys (67.1%,64.1%, χ 2=4.75, P <0.05). Multi factor Logistic regression analysis showed that ethnicity and HPV testing were related factors that affected college students willingness to vaccinate (minority: OR boy =1.23, OR girl =1.35; previous HPV testing: OR boy =0.56, OR girl =0.59); boys willingness to vaccinate was related to the number of sexual partners ( OR =0.60), family history of cancer ( OR =0.65), and sexual behavior related HPV knowledge scores ( OR =0.89), while girls willingness to vaccinate was related to bisexual sexual orientation ( OR =0.59), previous HIV testing ( OR =0.60), and HPV and vaccine basic knowledge scores ( OR =0.86) (all P <0.05).
Conclusions
College students in Guizhou Province have higher HPV vaccine related knowledge scores and are more willing to vaccinate, and those above are higher in girls than in boys. Health education content should be optimized based on gender differences, and promote the willingness and behavior of HPV vaccination among college students.
7.Anatomical features and surgical results of criss-cross heart: Five case reports
Chunzhen ZHANG ; Minhua FANG ; Yong ZHANG ; Xu ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(03):484-486
From June 2002 to December 2023, there were 5 patients with criss-cross hearts admitted to the General Hospital of Northern Theater Command, including 3 males and 2 females, aged 1.5 to 25 years, and weighing 13-49 kg. There were 5 patients of atrioventricular position, 3 patients of right ventricular loop, 2 patients of left ventricular loop, 3 patients of normal atrioventricular connection, and 2 patients of inconsistent connection. Combined intracardiac malformations: 1 patient of simple ventricular septal defect combined with pulmonary hypertension, 1 patient of corrected transposition of the great arteries combined with ventricular septal defect, atrial septal defect, and pulmonary artery stenosis, 1 patient of corrected transposition of the great arteries combined with ventricular septal defect, atrial septal defect, and left atrioventricular valve insufficiency, and 2 patients of right ventricular double outlet combined with ventricular septal defect and pulmonary artery stenosis. The surgical methods included 2 patients of intracardiac anatomical correction, 1 patient of bidirectional vena cava pulmonary artery anastomosis, and 2 patients of total extracardiac ductal cava pulmonary artery anastomosis. All 5 patients were discharged smoothly.
8.The biological mechanism and clinical application of bone shell technique in alveolar bone augmentation
CHEN Zetao ; GAO Xiaomeng ; OUYANG Zhaoguang ; AO Yong ; GUO Xinyu
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(4):315-327
A portion of patients undergoing implant restoration require bone augmentation procedures to ensure that there is sufficient bone volume around the implant. For the patients with horizontal bone ridge defects at edentulous sites, with or without mild to moderate vertical bone defects, the shell technique serves as a reliable and minimally invasive bone augmentation method with effective space maintenance. The shell technique involves fixating 1 mm cortical bone blocks to the recipient site, using retention screws and filling the gap between the bone block and recipient bed with particulate bone substitute materials, and covering the barrier membrane to achieve bone augmentation. The overlying tension-free soft tissue closure seals the surgical site while local peripheral blood releases osteoclasts and cytokines that gradually degrade the bone block. The rigid fixation of the bone block ensures a stable internal environment for osteogenesis and a new bone regeneration cycle. Although this technique demonstrates favorable bone augmentation outcomes, it is highly technique-sensitive. There are certain differences in the application scenarios and osteogenic processes for autologous and allogeneic bone shells. The selection of bone blocks and particulate bone substitute materials significantly influences the osteogenic biological process and the predictability of bone augmentation results. Complications associated with the shell technique possess distinct characteristics, such as the immunogenicity of allogeneic bone fragments, soft tissue cracking, and bone fragment loosening. Their prevention and subsequent management substantially impact the success rate of osteogenesis. This article delves into the biological mechanisms of osteogenesis in the bone block technique, summarizing the indications, clinical outcomes, classification of bone blocks, and surgical workflow management, as well as complication prevention and management, aiming to provide a reference for the future application and development of the bone shell technique.
9.Current quality status and management countermeasures of occupational health technical services in Zhejiang Province
Qiuliang XU ; Feng HAN ; Peng WANG ; Zhen ZHOU ; Fei LI ; Hongwei XIE ; Yong HU ; Weiming YUAN ; Lifang ZHOU ; Hua ZOU
Journal of Environmental and Occupational Medicine 2026;43(3):341-346
Background The quality of occupational health technical services is directly linked to the protection of workers' health rights and the efficacy of occupational disease prevention and control. However, the industry still faces critical challenges: sporadic instances of institutional non-compliance and persistent irregularities in professional practice continue to undermine overall service performance. Objective To assess the current quality status of occupational health technical services in Zhejiang Province and propose countermeasures for quality improvement, providing a scientific basis for policy optimization and service delivery quality enhancement. Methods A total of 69 occupational health technical service institutions in Zhejiang Province that obtained formal accreditation as of April 30, 2024, were sampled, including 3 public institutions and 66 private institutions (comprising 3 formerly Class-A, 28 formerly Class-B, 11 formerly Class-C, and 24 newly certified institutions). Following the Technical Protocol for Quality Monitoring of Occupational Health Technical Service in Zhejiang Province and the Technical Protocol for Proficiency Testing of Occupational Health Detection in Zhejiang Province, a quality assessment task force comprising national and provincial experts was established. Evaluation was conducted across four dimensions: qualification maintenance and compliance, standardization of technical services, authenticity of technical services, and proficiency testing, utilizing a combination of document review, on-site inspections, and technical skill assessments. Results The occupational health technical service institutions in Zhejiang Province were predominantly private entities (82.5%), with significant disparities in overall service quality. The pass rates for qualification maintenance and compliance, technical service standardization, technical service authenticity, and the excellence rate for laboratory proficiency testing were 81.5%, 80.7%, 97.3%, and 90.4%, respectively. Regarding qualification maintenance, the pass rates for "environmental conditions" (49.8%, 56.7%) and "instrumentation and equipment" (58.2%、65.6%) were significantly lower for formerly Class-C and newly certified institutions compared to other categories. In terms of technical standardization, "standardized on-site inspections" recorded the lowest pass rate (67.4%), with newly certified institutions at only 48.0%. Regarding technical service authenticity, formerly Class-C institutions exhibited issues such as missing raw chromatograms for blank samples (85.7% pass rate). In laboratory proficiency testing, public and formerly Class-A institutions achieved 100% excellence rates, but the performance of formerly Class-C and newly certified institutions was comparatively weak; specifically, the failure rate for organic analysis in formerly Class-C institutions reached 20%; the failure rate for dust testing items in newly certified institutions was 10.3%. Conclusion The overall quality of occupational health technical services in Zhejiang Province still requires significant improvement, particularly in basic institutional conditions, the standardization of on-site inspections, and laboratory proficiency in organic and dust analysis. Formerly Class-C and newly certified institutions should be the primary focus of quality management efforts. Differentiated regulatory strategies are recommended, alongside strengthening interim and ex-post supervision to gradually enhance the quality of occupational health technical services across all institutions.
10.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.


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