1.Impact of Maxing Kugan Decoction on Inflammatory Response and Apoptosis in Oleic Acid-induced Acute Lung Injury in Rats via p38 MAPK/NF-κB Signaling Pathway
Taiqiang JIAO ; Yi NAN ; Ling YUAN ; Jiaqing LI ; Yang NIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):108-116
ObjectiveTo investigate the effects of Maxing Kugan decoction (MKD) on inflammatory response and apoptosis in rats with oleic acid (OA)-induced acute lung injury (ALI) and explore its mechanism of action. MethodsSixty Sprague-Dawley (SD) rats were randomly assigned into six groups: a control group, a model group, a dexamethasone-treated group (2 mg·kg-1), and three MKD-treated groups at low, medium, and high doses (3.1, 6.2,12.4 g·kg-1). Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA (0.2 mL·kg-1). Twelve hours after modeling, blood gas analyses were conducted, and the wet-to-dry (W/D) weight ratio of lung tissue was measured for each group. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin (HE) staining and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assays, and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the control group, the model group exhibited a significant decrease in partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), along with a marked increase in partial pressure of carbon dioxide (PaCO2) and lung W/D ratio (P<0.01). Additionally, levels of TNF-α, IL-6, and IL-1β in BALF were significantly elevated (P<0.01). Histopathological analysis of lung tissue showed significant inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK, NF-κB p65, inhibitor of NF-κB (IκBα), B-cell lymphoma-2 associated x protein (Bax), and Caspases-3, as well as the protein expression levels of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3, while the mRNA and protein expression of Bcl-2 was downregulated (P<0.01). Compared with the model group, MKD significantly elevated PaO2, SaO2, and PaO2/FiO2 while reducing PaCO2 and W/D ratio in rats (P<0.01). It also greatly reduced TNF-α, IL-6, and IL-1β levels in BALF (P<0.01) and alleviated inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Additionally, it downregulated the mRNA expression of p38 MAPK, NF-κB p65, IκBα, Bax, Caspases-3, as well as protein expression of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3 in lung tissue (P<0.05, P<0.01), while significantly upregulating mRNA and protein expression of Bcl-2 (P<0.01). ConclusionMKD exerts a protective effect on OA-induced ALI rats, potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.
2.Impact of Maxing Kugan Decoction on Inflammatory Response and Apoptosis in Oleic Acid-induced Acute Lung Injury in Rats via p38 MAPK/NF-κB Signaling Pathway
Taiqiang JIAO ; Yi NAN ; Ling YUAN ; Jiaqing LI ; Yang NIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):108-116
ObjectiveTo investigate the effects of Maxing Kugan decoction (MKD) on inflammatory response and apoptosis in rats with oleic acid (OA)-induced acute lung injury (ALI) and explore its mechanism of action. MethodsSixty Sprague-Dawley (SD) rats were randomly assigned into six groups: a control group, a model group, a dexamethasone-treated group (2 mg·kg-1), and three MKD-treated groups at low, medium, and high doses (3.1, 6.2,12.4 g·kg-1). Each group was administered either an equivalent volume of normal saline or the corresponding concentration of MKD by gavage for seven consecutive days. The model group and each administration group were used to establish the ALI model by tail vein injection of OA (0.2 mL·kg-1). Twelve hours after modeling, blood gas analyses were conducted, and the wet-to-dry (W/D) weight ratio of lung tissue was measured for each group. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) of the rats. Cell damage and apoptosis in lung tissue were examined via hematoxylin-eosin (HE) staining and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assays, and the results were subsequently scored. The expression levels of the p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway and apoptosis-related proteins and mRNAs were assessed using Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the control group, the model group exhibited a significant decrease in partial pressure of oxygen (PaO2), blood oxygen saturation (SaO2), and oxygenation index (PaO2/FiO2), along with a marked increase in partial pressure of carbon dioxide (PaCO2) and lung W/D ratio (P<0.01). Additionally, levels of TNF-α, IL-6, and IL-1β in BALF were significantly elevated (P<0.01). Histopathological analysis of lung tissue showed significant inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Pronounced increases were observed in the mRNA expression levels of p38 MAPK, NF-κB p65, inhibitor of NF-κB (IκBα), B-cell lymphoma-2 associated x protein (Bax), and Caspases-3, as well as the protein expression levels of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3, while the mRNA and protein expression of Bcl-2 was downregulated (P<0.01). Compared with the model group, MKD significantly elevated PaO2, SaO2, and PaO2/FiO2 while reducing PaCO2 and W/D ratio in rats (P<0.01). It also greatly reduced TNF-α, IL-6, and IL-1β levels in BALF (P<0.01) and alleviated inflammatory infiltration, tissue edema, alveolar septal thickening, and apoptosis of lung tissue. Additionally, it downregulated the mRNA expression of p38 MAPK, NF-κB p65, IκBα, Bax, Caspases-3, as well as protein expression of p-p38 MAPK, p-NF-κB p65, p-IκBα, Bax, Caspases-3, and cleaved Caspases-3 in lung tissue (P<0.05, P<0.01), while significantly upregulating mRNA and protein expression of Bcl-2 (P<0.01). ConclusionMKD exerts a protective effect on OA-induced ALI rats, potentially through the regulation of the p38 MAPK/NF-κB signaling pathway to inhibit inflammation and apoptosis.
3.Research progress of nano drug delivery system based on metal-polyphenol network for the diagnosis and treatment of inflammatory diseases
Meng-jie ZHAO ; Xia-li ZHU ; Yi-jing LI ; Zi-ang WANG ; Yun-long ZHAO ; Gao-jian WEI ; Yu CHEN ; Sheng-nan HUANG
Acta Pharmaceutica Sinica 2025;60(2):323-336
Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.
4.Usefulness of intraoperative choledochoscopy in laparoscopic subtotal cholecystectomy for severe cholecystitis
Rui-Hui ZHANG ; Xiang-Nan WANG ; Yue-Feng MA ; Xue-Qian TANG ; Mei-Ju LIN ; Li-Jun SHI ; Jing-Yi LI ; Hong-Wei ZHANG
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):192-198
Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.
5.Usefulness of intraoperative choledochoscopy in laparoscopic subtotal cholecystectomy for severe cholecystitis
Rui-Hui ZHANG ; Xiang-Nan WANG ; Yue-Feng MA ; Xue-Qian TANG ; Mei-Ju LIN ; Li-Jun SHI ; Jing-Yi LI ; Hong-Wei ZHANG
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):192-198
Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.
6.Usefulness of intraoperative choledochoscopy in laparoscopic subtotal cholecystectomy for severe cholecystitis
Rui-Hui ZHANG ; Xiang-Nan WANG ; Yue-Feng MA ; Xue-Qian TANG ; Mei-Ju LIN ; Li-Jun SHI ; Jing-Yi LI ; Hong-Wei ZHANG
Annals of Hepato-Biliary-Pancreatic Surgery 2025;29(2):192-198
Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.
7.Association analyses of early medication clocking-in trajectory with smart tools and treatment outcome in pulmonary tuberculosis patients
Chunhua XU ; Zheyuan WU ; Yong WU ; Qing WANG ; Zichun WANG ; Nan QIN ; Xinru LI ; Yucong YAO ; Kehua YI ; Yi HU
Shanghai Journal of Preventive Medicine 2025;37(3):210-214
ObjectiveTo construct a group-based trajectory model (GBTM) for early medication adherence check-in, and to analyze the relationship between different trajectories and treatment outcomes in tuberculosis patients using data that were generated from smart tools for monitoring their medication adherence and check-in. MethodsFrom October 1, 2022 to September 30, 2023, a total of 163 pulmonary tuberculosis patients diagnosed in Fengxian District were selected as the study subjects. The GBTM was utilized to analyze the weekly active check-in trajectories of the subjects during the first 4 weeks and establish different trajectory groups. The χ² tests were employed to compare the differences between groups and logistic regression analysis was conducted to explore the relationship between different trajectory groups and treatment outcomes. ResultsA total of four groups were generated by GBTM analyses, of which a low level of punch card was maintained in group A, 6% of the drug users increased rapidly from a low level in group B, 17% of drug users increased gradually from a low level in group C, and 18% of drug users maintained a high level of punch card in group D. The trajectory group was divided into two groups according to homogeneity, namely the low level medication punch card group (group A) and the high level medication punch card group (group B, group C, and group D). The results of multivariate logistic regression analyses revealed that low-level medication check-in (OR=3.250, 95%CI: 1.089‒9.696), increasing age (OR=1.030, 95%CI: 1.004‒1.056), and not undergoing sputum examination at the end of the fifth month (OR=2.746, 95%CI: 1.090‒7.009) were significantly associated with poor treatment outcomes. ConclusionThe medication check-in trajectory of pulmonary tuberculosis patients within the first 4 weeks is correlated with adverse outcomes, or namely consistent low-level medication adherence check-ins are associated with poor treatment outcomes, while high-level medication adherence check-ins are associated with a lower incidence of adverse outcomes.
8. Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model
Yu-Han WANG ; Ya-Ping XU ; Nan LI ; Ting-Ting CHEN ; Ling LI ; Ping-Ping GAO ; Wei WEI ; Wu-Yi SUN ; Hua WANG
Chinese Pharmacological Bulletin 2024;40(1):189-194
Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2
9. Research progress of Parkin protein regulating mitochondrial homeostasis through ubiquitination in cardiovascular diseases
Ke-Juan LI ; Jian-Shu CHEN ; Yi-Xin XIE ; Jia-Le BU ; Xiao-Wei ZHANG ; Yong-Nan LI
Chinese Pharmacological Bulletin 2024;40(2):224-228
In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.
10.Effect of type of carrier material on the in vitro properties of solid dispersions of progesterone
Jing-nan QUAN ; Yi CHENG ; Jing-yu ZHOU ; Meng LI ; Zeng-ming WANG ; Nan LIU ; Zi-ming ZHAO ; Hui ZHANG ; Ai-ping ZHENG
Acta Pharmaceutica Sinica 2024;59(3):735-742
This study investigated the effect of different carrier materials on the

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