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.Discovery and investigation of six polio vaccine derived viruses in Guangzhou City
Min CUI ; Chunhuan ZHANG ; Wei ZHANG ; Jun LIU ; Jialing LI ; Jianxiong XU ; Wenji WANG ; Qing HE ; Lihong NI ; Xuexia YUN ; Huanying ZHENG
Journal of Public Health and Preventive Medicine 2025;36(2):22-25
Objective To understand the surveillance situation of poliovirus in Guangzhou from 2011 to 2024, and to further strengthen polio surveillance and ensure the continued maintenance of a polio-free status. Methods An analysis was conducted on the discovery and investigation results of six cases of vaccine-derived poliovirus (VDPV) detected in Guangzhou. Results A total of 6 VDPV incidents were reported in Guangzhou from 2011 to June 2024, among which 5 incidents were from sewage sample testing in the Liede Sewage Treatment Plant in Guangzhou, all of which were confirmed as VDPV, with 1 for type I, 1 for type II, and 3 for type III. In addition, one confirmed HFMD case was identified as a type VDPV II carrier. No presence of any wild poliovirus (WPV), VDPV cases, or circulating VDPV (cVDPV) was reported. Conclusion Guangzhou City has maintained a high level of vigilance and effectiveness in the monitoring and prevention of polio. Continuously strengthening the construction of the polio monitoring network, optimizing vaccination strategies, and comprehensively improving public health awareness are still the focus of the prevention and control work in the future.
4.Efficacy of pelvic floor optimization training of Yun-type aided with myoelectric biofeedback in the treatment of mild to moderate female stress urinary incontinence
Xiaoxiang WAN ; Wei JIAO ; Chaoliang SHI ; Jiawei WANG ; Jialing YAO ; Yangyun WANG ; Xilong WANG
Journal of Modern Urology 2025;30(5):390-394
Objective: To explore the efficacy of pelvic floor optimization training of Yun-type with the aid of myoelectric biofeedback in the treatment of mild to moderate female stress urinary incontinence (SUI). Methods: Female SUI patients treated in our hospital during Jan.and Oct.2024 were included as the research subjects.They were randomly divided into the control group (n=47) and observation group (n=48) by random number method.The control group received conventional Yun-type pelvic floor optimization training,while the observation group received Yun-type pelvic floor optimization training assisted with myoelectric biofeedback.The total treatment course lasted for 12 weeks.The clinical efficacy,as well as the changes in international consultation on incontinence questionnaire for symptoms and impact (ICI-Q-SF),incontinence quality of life (I-QoL),female sexual function index (FSFI),and pelvic floor electromyographic values before and after treatment were compared. Results: The total effective rate of the observation group was 93.6%,which was significantly higher than that of the control group (79.2%,P<0.05).After 12 weeks of treatment,the ICI-Q-SF [(6.12±1.11) vs. (6.97±1.24)],I-QoL [(85.05±4.51) vs. (82.14±4.60)],and FSFI [(30.01±4.10) vs. (26.32±3.32)] scores of the observation group were significantly better than those of the control group (P<0.05).After 12 weeks of treatment,the myoelectric values of the pelvic floor muscles of the observation group at the pre-rest stage,fast muscle (type Ⅱ muscle) stage,slow muscle (type Ⅰ muscle) stage,endurance test stage,and post-rest stage were significantly improved compared with those before treatment and were greatly enhanced compared with those of the control group (P<0.05).No serious adverse reactions occurred in either groups during treatment and follow-up. Conclusion: The Yun-type pelvic floor optimization training assisted with myoelectric biofeedback can precisely enhance the therapeutic effects of the conventional Yun-type pelvic floor optimization training,and significantly improve the female sexual function index.It is worthy of clinical promotion and application.
5.Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regeneration via DUSP1 ADP-ribosylation-mediated p38 MAPK phosphorylation.
Luxun TANG ; Yu SHI ; Qiao LIAO ; Feng WANG ; Hao WU ; Hongmei REN ; Xuemei WANG ; Wenbin FU ; Jialing SHOU ; Wei Eric WANG ; Pedro A JOSE ; Yongjian YANG ; Chunyu ZENG
Acta Pharmaceutica Sinica B 2025;15(1):256-277
The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.
6.Recent advances, strategies, and future perspectives of peptide-based drugs in clinical applications.
Qimeng YANG ; Zhipeng HU ; Hongyu JIANG ; Jialing WANG ; Han HAN ; Wei SHI ; Hai QIAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):31-42
Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans
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Peptides/pharmacology*
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Animals
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Neoplasms/drug therapy*
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Drug Discovery
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Neurodegenerative Diseases/drug therapy*
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Diabetes Mellitus/drug therapy*
7.Treatment of chronic sinus tract leakage at rectal anastomosis with anal fistula endoscopy
Liqiang JI ; Jialing ZHOU ; Cheng XIN ; Shuyuan LI ; Ye WANG ; Zheng LOU ; Wei ZHANG
Chinese Journal of Gastrointestinal Surgery 2024;27(10):1080-1082
Objective:To introduce the method of using anal fistula endoscope to treat chronic sinus tract leakage at rectal anastomosis site.Methods:We used anal fistula endoscopy to treat a patient with chronic sinus tract leakage after radical resection of rectal cancer, mainly including the following 5 steps: (1) establishing a water injection circulation system through the anus; (2) scraping off purulent coating and mucosa on the surface of the sinus tract with the brush; (3) hemostasis and removal of necrotic tissue with electrocoagulation rods; (4) filling the sinus tract with bioprotein gel; (5) compressing the sinus tract with transanal drainage tube.Results:The patient is a 70 year old male with rectal cancer. After undergoing 3D laparoscopic assisted radical resection of rectal cancer via abdominal anterior resection (Dixon's procedure) and diverting ileostomy surgery for more than 3 months, leakage of the rectal anastomosis was found through colonoscopy and anal iodine water contrast imaging .The patient started eating and flowing juice 6 hours after surgery, got out of bed 24 hours after surgery, and was discharged 48 hours after the removal of the anal canal. Three months after surgery, colonoscopy and transanal iodine hydrography showed that the sinus repair was intact. The diverting ileostomy was reduced 4 months after surgery.Conclusion:Anal fistula endoscope is safe and feasible for the treatment of chronic sinus tract anastomotic leakage in selected patients.
8.Accuracy of portable hemoglobinometer in maintenance hemodialysis patients
Xiaohao ZHANG ; Fanglin TANG ; Jialing RAO ; Yuanqing LI ; Wei LI ; Cailian CHENG ; Hui PENG
Chinese Journal of Nephrology 2024;40(1):49-52
This study aims to evaluate the accuracy of portable hemoglobinometer (Hemocue Hb 201+ hemoglobin analyzer) in patients with maintenance hemodialysis (MHD) and its diagnostic value for anemia. The data of venous hemoglobulin (Hb) and fingertip capillary hemoglobulin (DHb) in MHD patients from Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed, and the correlation and difference between DHb and Hb and the accuracy of DHb in the diagnosis of anemia were evaluated. A total of 105 patients were included in the study. There was no significant difference between the paired DHb and Hb [(109±21) g/L vs. (108±20) g/L, t=-1.284, P=0.202]. Pearson correlation analysis showed that DHb was positively correlated with Hb ( r=0.929, P<0.001). Linear regression analysis showed that DHb and Hb met the regression equation Hb=0.88×DHb+12.23, and P<0.001. Bland-Altman analysis showed that the differences between the paired DHb and Hb was (1.0±7.8) g/L with the limit of agreement as (-14.2, 16.2) g/L. The mean percentage of the differences in Hb was 1% with limit of agreement as (-13.7%, 15.7%). A DHb of >110 g/L was 0.90 sensitive and 0.83 specific to identify patients with an Hb >110 g/L and its positive and negative predictive values were 0.84 and 0.90, respectively. It suggests that, in MHD patients, Hemocue Hb 201+ analyzer shows good accuracy, and can be used to monitor the Hb trend and serve as a screen method for those reaching target Hb.
9.Exploring the Mechanism of Sini San Formula on Ulcerative Colitis and Depression Through"Homotherapy for Heteropathy"Based on Network Pharmacology and Molecular Docking
Jialing SHAN ; Weiqiong HU ; Qin XIE ; Wei BAI ; Tianyu HU ; Yanni LYU ; Mingjin JIANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):83-91
Objective To investigate the mechanism of Sini San Formula in the treatment of ulcerative colitis and depression through"homotherapy for heteropathy"based on network pharmacology and molecular docking.Methods The TCMSP database was used to obtain the potential active components and their related targets;GeneCards,CTD,and TTD databases were used to screen the disease-related targets of ulcerative colitis and depression;the intersection of the predicted targets of the active components and the disease-related targets was used to obtain the potential targets(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,and Cytoscape 3.7.2 software to construct a"Chinese medicinals-active components-diseases-common targets"network to analyze the core components;importing the common targets into the STRING database,constructing a common protein-protein interaction(PPI)network.The GO function and KEGG pathway enrichment of the shared targets were analyzed by DAVID database,and molecular docking between the core components and the key targets was verified.Results A total of 136 active components of Sini San Formula were obtained,and 220 potential targets of action(shared targets)for the treatment of ulcerative colitis and depression by Sini San Formula,involving 657 biological processes,70 cellular components,147 molecular functions and 133 signaling pathways.The screening yielded core active compounds such as quercetin,kaempferol,lignans,naringenin,7-methoxy-2-methylisoflavone,key target proteins such as JUN,MAPK3,STAT3,AKT1,and MAPK1,as well as signaling pathways such as TNF,IL-17,Th17 cellular differentiation,HIF-1,and Toll-like receptor.Five potential key targets have strong binding activity to quercetin,kaempferol,lignans and naringenin.Conclusion Sini San Formula may act on key targets such as JUN,MAPK3,STAT3,AKT1,MAPK1,etc.through active components such as quercetin,kaempferol,lignocerotonin,naringenin,etc.,and play the role of"homotherapy for heteropathy"for ulcerative colitis and depression through the signaling pathways such as TNF,IL-17,HIF-1,Toll-like receptor and Th17 cell differentiation.
10.Treatment of chronic sinus tract leakage at rectal anastomosis with anal fistula endoscopy
Liqiang JI ; Jialing ZHOU ; Cheng XIN ; Shuyuan LI ; Ye WANG ; Zheng LOU ; Wei ZHANG
Chinese Journal of Gastrointestinal Surgery 2024;27(10):1080-1082
Objective:To introduce the method of using anal fistula endoscope to treat chronic sinus tract leakage at rectal anastomosis site.Methods:We used anal fistula endoscopy to treat a patient with chronic sinus tract leakage after radical resection of rectal cancer, mainly including the following 5 steps: (1) establishing a water injection circulation system through the anus; (2) scraping off purulent coating and mucosa on the surface of the sinus tract with the brush; (3) hemostasis and removal of necrotic tissue with electrocoagulation rods; (4) filling the sinus tract with bioprotein gel; (5) compressing the sinus tract with transanal drainage tube.Results:The patient is a 70 year old male with rectal cancer. After undergoing 3D laparoscopic assisted radical resection of rectal cancer via abdominal anterior resection (Dixon's procedure) and diverting ileostomy surgery for more than 3 months, leakage of the rectal anastomosis was found through colonoscopy and anal iodine water contrast imaging .The patient started eating and flowing juice 6 hours after surgery, got out of bed 24 hours after surgery, and was discharged 48 hours after the removal of the anal canal. Three months after surgery, colonoscopy and transanal iodine hydrography showed that the sinus repair was intact. The diverting ileostomy was reduced 4 months after surgery.Conclusion:Anal fistula endoscope is safe and feasible for the treatment of chronic sinus tract anastomotic leakage in selected patients.


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