1.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.
2.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.
3.Value of immunoglobulin G/immunoglobulin M ratio in predicting the prognosis of patients with initially unresectable hepatocellular carcinoma treated by transcatheter arterial chemoembolization combined with tyrosine kinase inhibitor and programmed cell death protein-1 inhibitor
Xingzhi LI ; Wei LUO ; Yuan FENG ; Yu CAI ; Xiaohong LIU ; Feixiang WU ; Yong PENG
Journal of Clinical Hepatology 2026;42(1):117-124
ObjectiveTo investigate the association between immunoglobulin G (IgG)/immunoglobulin M (IgM) ratio and prognosis in patients with initially unresectable hepatocellular carcinoma (iuHCC) receiving TTP triple therapy with transcatheter arterial chemoembolization (TACE), tyrosine kinase inhibitor (TKI), and programmed cell death protein-1 (PD-1) inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, from November 2019 to December 2022, and according to IgG/IgM ratio, they were divided into high IgG/IgM group (IgG/IgM ratio >13.23) and low IgG/IgM group (IgG/IgM ratio ≤13.23). The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis, and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival (OS). ResultsThe 151 patients had a median OS of 26.7 months (95% confidence interval [CI]: 19.8-not reached) and a median progression-free survival of 12.5 months (95%CI: 10.4 — 15.8). The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group (all P>0.05). There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group (20.6 months vs not reached, P=0.016). In both the high IgG/IgM group and the low IgG/IgM group, salvage hepatectomy was significantly associated with the improvement in OS (χ2=8.297 and 10.307, both P<0.05). The multivariate analysis showed that high IgG/IgM ratio (hazard ratio [HR]=1.799, 95%CI: 1.077 — 3.006, P=0.025), baseline alpha-fetoprotein >400 ng/mL (HR=1.762, 95%CI: 1.017 — 3.050, P=0.043), and BCLC stage (HR=2.265, 95%CI: 1.212 — 4.232, P=0.010) were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy, and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.
4.Optimization of the Extraction Process of Changyan Heji Ⅱ Based on UPLC-Q-TOF-MS/MS Combined with Response Surface Method and Principal Component Analysis
Shulin WANG ; Jing SHANG ; Wenjun LIU ; Zerong CAI ; Mengyu QIAN ; Xiaoxin HU ; Liang CAO ; Zhenz-hong WANG ; Wei XIAO
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(4):501-512
OBJECTIVE To establish a extraction process of Changyan Heji Ⅱ(CYHJ-Ⅱ)based on UPLC-Q-TOF-MS/MS technology combined with response surface analysis,and to optimize the extraction process.METHODS The chemical components in CYHJ-Ⅱ were qualitatively analyzed by UPLC-Q-TOF-MS/MS technology,and the chemical components with good linear relation-ship in mass spectrometry response were selected as process investigation indicators;the extraction process parameters(water addition amount,extraction time and soaking time)were investigated by Box-Behnken design;the comprehensive score was obtained by princi-pal component analysis(PCA),and the optimal process was determined by the comprehensive score combined with response surface a-nalysis.RESULTS Through qualitative analysis,110 components were inferred and identified from CYHJ-Ⅱ,including 2 organic acids,82 flavonoids,13 terpenoids,and 13 alkaloids.Based on the results of qualitative analysis,48 index components with good lin-ear relationships were derived by UPLC-Q-TOF-MS/MS combined with Masshunter mass spectrometry data analysis software.PCA was performed and the comprehensive score was calculated.Response surface analysis was performed with the comprehensive score as an indicator.The optimal extraction process obtained by combining the response surface prediction results and actual production was:soaking for 45 min,8 times the amount of solvent,2 extractions,each time for 120 min.CONCLUSION This study provides a new idea for the investigation of the extraction process of traditional Chinese medicine compound prescriptions and expands a new method for the development of traditional Chinese medicine compound prescriptions.
5.Expert consensus on infection prevention and control of Creutzfeldt-Jakob disease in medical institutions
Tianxiang GE ; Yangyang JIA ; Chunhui LI ; Jianrong HUANG ; Xiujuan MENG ; Xiaodong GAO ; Jingping ZHANG ; Fu QIAO ; Lijuan XIONG ; Hui LIANG ; Wei LI ; Haiyan LOU ; Wenjuan WU ; Tianxin XIANG ; Jiansen CHEN ; Biao ZHU ; Kaijin XU ; Zhihui ZHOU ; Hongliu CAI ; Meihong YU ; Yan ZHANG ; Yanwan SHANGGUAN ; Haiting FENG ; Hangping YAO ; Lei GUO ; Tieer GAN ; Weihong ZHANG ; Jimin SUN ; Ye LU ; Qun LU ; Meng CAI ; Jin SHEN ; Yunsong YU ; Anhua WU ; Liu-yi LI ; Tingting QU
Chinese Journal of Infection Control 2025;24(4):437-450
Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.
6.Research progress on activation of patients with breast cancer
Huiyan CHENG ; Yuzhu LIU ; Yingjie CAI ; Yufei GUO ; Ran WEI ; Tieying SHI
Chinese Journal of Practical Nursing 2025;41(33):2634-2641
Breast cancer is the number one killer threatening women's health, and the side effects caused by its treatment seriously affect patients' quality of life. Research has confirmed that good patient activation can effectively improve the quality of life of breast cancer patients, and it is of great significance to improve the quality of care and the recovery process of breast cancer patients.The purpose of this study is to review the current situation, assessment tools, influencing factors, and interventions of breast cancer patients' activation, in order to provide reference for researchers to conduct patient activation-related studies in the future.
7.Traditional Chinese medicine syndrome analysis of malnutrition, sarcopenia, and frailty in older adult patients with pneumonia
Jingran CAO ; Qingsheng LUO ; Xiaoqiang CAI ; Wei LIU
Chinese Journal of Primary Medicine and Pharmacy 2025;32(9):1287-1291
Objective:To investigate the distribution of Traditional Chinese Medicine (TCM) syndromes in older adult patients with pneumonia who face nutritional risks, malnutrition, sarcopenia, and frailty, as well as the extent to which these syndromes affect their nutritional status.Methods:This study used a cross-sectional research design. A total of 1 263 older adult patients with pneumonia who received treatment at the Department of Traditional Chinese Medicine, The Second Hospital of Tianjin Medical University, from July 2021 to July 2024 were included in this study. These patients underwent TCM syndrome differentiation and nutritional assessments. The top 10 distribution patterns of TCM syndromes related to nutritional risk, malnutrition, sarcopenia, and frailty were identified. Logistic regression analysis was performed to analyze the effect of each syndrome pattern on nutritional risk, malnutrition, sarcopenia, and frailty. The odds ratio ( OR) value was used as the effect indicator of effect, with an OR > 1 indicating that the syndrome pattern is a risk factor for nutritional status; the larger the value, the higher the risk. Results:In older adults with pneumonia, the TCM syndrome patterns most commonly associated with nutritional risk, malnutrition, sarcopenia, and frailty were concentrated in phlegm-damp accumulation, phlegm-heat obstructing the lung, qi and blood deficiency, qi deficiency with blood stasis, qi and yin depletion, yang deficiency with water retention, spleen-stomach deficiency, lung qi depletion, and kidney deficiency with failure to grasp qi. Qi deficiency with blood stasis ( OR = 3.70) and qi and blood deficiency ( OR = 4.90) were risk factors for malnutrition. Phlegm-damp accumulation ( OR = 3.46), qi deficiency with blood stasis ( OR = 3.87), and qi and blood deficiency ( OR = 4.52) were risk factors for sarcopenia. Phlegm-damp accumulation ( OR = 2.63), phlegm-heat obstructing the lung ( OR = 3.14), qi deficiency with blood stasis ( OR = 5.78), and qi and blood deficiency ( OR = 6.33) were risk factors for frailty. Conclusions:Phlegm-dampness accumulation, phlegm-heat obstructing the lungs, deficiency of both qi and blood, and qi deficiency with blood stasis are all risk factors for nutritional risks, malnutrition, sarcopenia, and frailty in older adults. Patients with pneumonia exhibiting these patterns should pay special attention to their nutritional status, and early nutritional intervention should be implemented to prevent adverse clinical outcomes.
8.Comparison of clinical efficacy of different mucosal incision methods in endoscopic submucosal dissection for the treatment of gastric submucosal tumors
Xinglin CHEN ; Ke WEI ; Yuanyuan CAI ; Qinqin QI ; Zhemin WANG ; Liuyong CHEN ; Bin LIU
China Journal of Endoscopy 2025;31(3):7-12
Objective To explore the clinical efficacy of different mucosal incision methods in endoscopic submucosal dissection(ESD)for the treatment of gastric submucosal tumors.Methods A retrospective analysis was conducted on the clinical data of 30 patients with gastric submucosal tumors treated with ESD from July 2022 to March 2024.They were divided into a circular group(n=15)and a longitudinal group(n=15)based on different mucosal incision methods.Then compare the pathological data,clinical efficacy,surgical outcomes,and complications between the two groups.Results There were no statistically significant differences between the two groups in length of hospital stay,hospitalization costs,lesion diameter,lesion location and lesion nature(P>0.05).The surgical time of the longitudinal group was significantly shorter than that of the circular group,and the difference was statistically significant(P<0.05);There was no statistical significant in the incidence of intraoperative complications in the longitudinal group and the circular group(P>0.05);The complete resection rate of the longitudinal group was lower than that of the circular group,but the difference was not statistically significant(P>0.05).Conclusion ESD treatment for gastric submucosal tumors is safe and effective,and the longitudinal incision can shorten the surgical time compared to the circular incision.Both methods have the characteristics of low incidence of complications and high complete resection rate,and are worthy of clinical application.
9.Pedigree analysis and prenatal diagnosis in a family with congenital ectopia lentis
Guixian PAN ; Sitao LI ; Hu HAO ; Wei LIU ; Qiuping YANG ; Xin XIAO ; Yao CAI
The Journal of Practical Medicine 2025;41(6):824-828
Objective To analyze the clinical characteristics associated with prenatal diagnosis of FBN 1 gene mutations in a family.This study explores the correlation between gene mutations and their corresponding clini-cal phenotypes,emphasizing the significance of prenatal diagnosis in providing a foundation for subsequent follow-up and intervention.Methods Genomic DNA was extracted from the amniotic fluid of the fetus and the peripheral blood of the parents for trio-whole exome sequencing.The candidate variant identified was subsequently validated using Sanger sequencing.Results The pedigree comprised four generations and nine family members,with four individuals exhibiting slender limbs and toes.Among these,three showed congenital lens dislocation or subluxation.No abnormalities in the cardiovascular system were observed.Genetic testing of symptomatic individuals revealed a heterozygous mutation(c.6158G>T)in the FBN 1 gene.Conclusions The FBN 1 c.6158G>T(p.C2053F)muta-tion was identified as the pathogenic variant responsible for the condition in this family,exhibiting autosomal domi-nant inheritance.To our knowledge,this is the first reported case of the FBN 1 c.6158G>T(p.C2053F)mutation in China.Prenatal diagnosis can facilitate early confirmation of the condition and provide a foundation for subsequent in-terventions and follow-up care.
10.Research status and development trends of dental pulpitis biomarkers
Hongyan LIU ; Yanling CAI ; Xi WEI
Chinese Journal of Stomatology 2025;60(11):1217-1224
Pulpitis is an inflammatory response of dental pulp tissue triggered by external stimuli such as bacterial infection, mechanical trauma, and iatrogenic injury. Accurate diagnosis of pulpitis is essential for the success of minimally invasive endodontic treatments. However, the current diagnostic framework lacks objective indicators capable of precisely assessing the severity of pulp inflammation. Recent studies have revealed that biomarkers such as matrix metalloproteinases, cytokines, chemokines, non-coding RNAs, growth factors, and signaling molecules are closely associated with the degree of pulp inflammation. These findings suggested that biomarker-based molecular diagnostics held significant promise for advancing precision and minimally invasive approaches in endodontics. This review systematically discusses the current research progress, challenges, and future directions of biomarkers in the diagnosis and treatment of pulpitis.

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