1.Clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists in China
Yunjin ZHANG ; Xiaorong WU ; Zhiyun HUANG ; Meiyan ZHANG ; Fan ZHANG ; Hongtao LIU
China Pharmacy 2026;37(2):142-148
OBJECTIVE To conduct a clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists (TPO-RA) approved in China, providing quantitative evidence for drug selection and therapeutic decision-making in medical institutions. METHODS Relevant data on Romiplostim for injection, Eltrombopag olamine tablets, Herombopag olamine tablets, Avatrombopag maleate tablets, and Lusutrombopag tablets were collected. Based on the Chinese Rapid Guide for Drug Evaluation and Selection in Medical Institutions (Second Edition), 12 formulations of these five TPO-RA were scored quantitatively and comparatively across five dimensions: pharmacological characteristics, efficacy, safety, cost-effectiveness, and other attributes. RESULTS The comprehensive scores of the 12 formulations ranged from 62.56 to 75.50 points, with most scoring ≥70 points. Using the highest-scoring formulation for each generic name as a representative, the overall rankings of the five TPO-RA were as follows: Lusutrombopag tablets (75.50 points), Eltrombopag olamine tablets (75.10 points), Avatrombopag maleate tablets (70.40 points), Romiplostim for injection (63.93 points), and Herombopag olamine tablets (63.52 points). Lusutrombopag tablets scored relatively high in pharmacological characteristics, safety, and cost-effectiveness, while Eltrombopag olamine tablets performed well in efficacy and cost-effectiveness. The other formulations showed varying scores across evaluation dimensions. CONCLUSIONS The five TPO-RA demonstrate favorable overall clinical value, with Lusutrombopag tablets and Eltrombopag olamine tablets ranking higher in comprehensive scores, these two drugs should be prioritized in drug selection and formula optimization by medical institutions.
2.Analysis of influencing factors for gastroesophageal reflux disease after laparoscopic Heller-Dor surgery for esophageal achalasia
Xuemei GUAN ; Fengru ZHANG ; Lihua DU ; Bo ZHANG ; Meiyan GAO ; Rongsheng ZHANG
Chinese Journal of Digestive Surgery 2025;24(10):1318-1325
Objective:To investigate the influencing factors for gastroesophageal reflux disease (GERD) after laparoscopic Heller-Dor surgery for esophageal achalasia.Methods:The retrospective case-control study was conducted. The clinical data of 210 patients with esophageal achalasia who were admitted to Shanxi Provincial Cancer Hospital from January 2021 to December 2023 were collected. There were 119 males and 91 females, aged (47±12)years. All patients underwent laparoscopic Heller-Dor surgery. Observation indicators: (1) surgical situations; (2) follow-up; (3) influencing factors for GERD after laparoscopic Heller-Dor surgery; (4) development and evaluation of a predictive model for GERD after laparoscopic Heller-Dor surgery. Univariate and multivariate analyses were performed using stepwise Logistic regression. Results of multivariate analysis were used to construct a nomogram in predicting GERD. The predictive performance was assessed using the area under the receiver operating characteristic curve. The calibration curve was used to evaluate the accuracy of the model, and the decision curve was used to assess the overall net benefit of the model.Results:(1) Surgical situations. All 210 patients underwent laparoscopic Heller-Dor surgery. The operation time was (128±31)minutes, volume of intraoperative blood loss was (25±9)mL, and length of lower esophageal sphincter (LES) myotomy was (5±3)cm. The length of low esophageal myotomy >6 cm was performed in 49 patients, and length of gastric fundus myotomy >2 cm was performed in 58 patients. Intraoperative mucosal perforation occurred to 3 patients and was repaired intraoperatively. One patient required conversion to open surgery. Postoperative complications occurred in 18 patients. The duration of postoperative hospital stay was (4.3±2.4)days. (2) Follow-up. All 210 patients were followed up for 4(range,7-33)months after surgery. During follow-up, 32 pati-ents had GERD, including 17 cases presenting dysphagia and 25 cases presenting acid regurgitation and heartburn (the same patient may have two symptoms). There were 29 cases with body mass index (BMI) >28 kg/m2. Symptom severity scores of 210 patients showed heartburn of 0.6(range, 0-3.0), reflux of 0.7(range, 0-3.0), chest pain of 0.4(range, 0-2.0), cough and hoarseness of 0.5(range, 0-2.0), nausea and vomiting 0.3(range, 0-2.0), dysphagia 0.8(range, 0-3.0). The LES pressure was (15±8)mmHg (1 mmHg=0.133 kPa), LES relaxation rate was 81%±13.0%, and integrated relaxation pressure was (9±6)mmHg. Esophageal manometry classification showed type Ⅰ, Ⅱ, and Ⅲ in 0, 8, and 0 patients, respectively. There were 208 patients achieved symptom relief after drug or symptomatic treatment. Only two patients with severe symptoms were unresponsive to medication and subsequently underwent surgery at another hospital, with symptoms improving postoperatively. (3) Influen-cing factors for GERD after laparoscopic Heller-Dor surgery. Results of multivariate analysis showed that male, smoking history, length of lower esophageal myotomy >6 cm, and postoperative BMI >28 kg/m2 were independent risk factors for GERD after laparoscopic Heller-Dor surgery ( odds ratio=4.02, 6.34, 5.41, 7.38, 95% confidence interval as 1.50-10.78, 3.31-12.31, 1.77-13.47, 2.80-15.42, P<0.05). (4) Development and evaluation of a predictive model for GERD after laparoscopic Heller-Dor surgery. A predictive nomogram model for GERD was constructed based on the results of multivariate analysis. The receiver operating characteristic curve of predictive nomogram model for GERD had an area under curve of 0.91 (95% confidence interval as 0.82-0.97), demonstrating good discrimination. The calibration curve showed good agreement between predicted and observed probabilities, with a mean absolute error of 0.033. The decision curve demonstrated that within a threshold probability range of 0.2-0.8, the predictive model had greater net benefit than "treat-all" or "treat-none" strategies, indicating clinical utility of this model in clinical decision. Conclusions:Male, smoking history, length of lower esophageal myotomy >6 cm, and postoperative BMI >28 kg/m2 are independent risk factors for GERD after laparoscopic Heller-Dor surgery for esophageal achalasia. The predictive model for GERD after laparoscopic Heller-Dor surgery based on these factors shows strong predictive accuracy.
3.Histomorphology of Colorectal Superficially Serrated Adenoma and the Role of RSPO2 and RSPO3 in its Carcinogenic Mechanism
Suming GAO ; Lin WANG ; Meiyan LIANG ; Zhenhua ZHANG ; Xiaosai CHEN ; Li LI
Chinese Journal of Gastroenterology 2025;30(1):32-37
Background:Colorectal cancer(CRC)is a major cause of cancer death worldwide,and about 30%to 35%of CRC arises from the serrated pathway.Aims:To analyze the clinicopathological and histomorphological characteristics of colorectal superficially serrated adenoma(SuSA),and to investigate the malignant transformation potential of SuSA and further elucidate the role of RSPO2 and RSPO3 in its carcinogenic mechanism.Methods:A total of 169 serrated colorectal lesions confirmed pathologically and fulfilling the inclusion criteria were collected from Shanxi Bethune Hospital from February 2019 to May 2023.Among them,there were 84 cases of SuSA,23 sessile serrated lesions(SSL),32 traditional serrated adenomas(TSA),and 30 hyperplastic polyps(HP).Thirty-nine cases of tubular adenoma(TA),32 CRC,and 33 normal colorectal mucosal tissues were served as controls.The clinicopathological and histomorphological parameters were collected and recorded.Immunohistochemical staining was used to detect the protein expressions of RSPO2,RSPO3,p53,MLH1 and β-catenin.Results:Patients with SuSA were male predominance,with a mean age of 51.89 years.The average diameter of the lesions was 0.20 cm,predominantly located in the left colon and rectum,and frequently complicated with other polyps/adenomas.The histomorphological features of SuSA were as follows:the glandular necks and crypt bases exhibited straight tubular structure with low-grade dysplasia;the superficial layer demonstrated a serrated architecture,with or without dysplasia,and contained a variable number of goblet cells.Immunohistochemically,there were no statistically significant differences in RSPO2,RSPO3,and p53 expressions between SuSA and TSA(all P>0.05).A strong positive correlation was observed between RSPO2 and RSPO3 in colorectal lesions,excluding HP.Expressions of MLH1 and β-catenin showed no statistically significant differences between SuSA and other colorectal lesions(all P>0.05).Conclusions:SuSAs are more common in males,occur mostly in the left colon and rectum,and are often associated with other polyps/adenomas.They might be precursors of KRAS-mutated TSA and microsatellite stable CRC with high malignant potential.RSPO2 and RSPO3 might play an important role in the carcinogenesis of SuSA.
4.Clinical application of dermatoscope combined with rapid frozen section examination in the treatment of head and facial skin tumors
Xuefeng FU ; Lei ZENG ; Yuan JIANG ; Meiyan WANG ; Bingjing JIANG ; Yanfei ZHANG
China Modern Doctor 2025;63(13):19-22
Objective To evaluate the application value of dermatoscope combined with rapid frozen section examination in the treatment of head and facial skin tumors.Methods A retrospective analysis was performed on 123 patients with head and facial skin masses admitted to Affiliated Jinhua Hospital,Zhejiang University School of Medicine from June 2019 to December 2023.Patients were divided into two groups according to their wishes.Patients in group A underwent preoperative dermoscopy combined with intraoperative rapid frozen section examination,and patients in group B underwent preoperative skin biopsy combined with intraoperative rapid frozen section examination.The diagnostic accuracy of two methods was compared.Results There were 81 patients in group A,including 39 basal cell carcinoma,25 squamous cell carcinoma,8 solar keratosis,5 seborrheic keratosis and 4 verrucous nevus.There were 42 patients in group B,including 25 basal cell carcinoma,13 squamous cell carcinoma and 4 solar keratosis.Both groups of patients successfully completed the operation,postoperative follow-up 6 months no recurrence.The accuracy of dermoscopy in the diagnosis of head and facial skin masses was 91.36%,and the accuracy of skin biopsy was 100%.There was no statistical significance between them(x2=2.407,P=0.121).Conclusion In surgical treatment of head and facial skin tumors,the diagnostic accuracy of preoperative dermoscopy combined with intraoperative rapid frozen section examination is high,and it is worthy of clinical promotion.
5.Visualization Analysis on Research Literature about the Essence of TCM Syndromes
Zhiyang LI ; Wanyi ZHANG ; Zhujun LIU ; Qing GAO ; Meiyan ZENG ; Qinghua PENG ; Houpan SONG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):56-62
Objective To analyze relevant literature on the essence of traditional Chinese medicine syndromes using bibliometric methods;To understand the current research status and hotspots in this field;To provide references for relevant research.Methods Research literature about the essence of TCM syndromes was retrieved from CNKI,VIP,Wanfang Data and CBM from 1st Jan.1979 to 30th June 2024.CiteSpace 6.2 software was used to conduct visualization analysis on authors,institutions,keywords,etc.Results A total of 695 articles were included,with an overall upward trend in publication volume followed by stabilization.The authors who published more articles included Luo Ren(13 articles),Zhao Xiaoshan(13 articles),Li Zegeng(12 articles),etc.The institutions with more publications included Shandong University of Traditional Chinese Medicine(35 articles),Beijing University of Chinese Medicine(33 articles),Chengdu University of Traditional Chinese Medicine(26 articles),etc.Institutions were clustered regionally,and cooperation was mostly between TCM universities and their affiliated hospitals,with less cross regional communication.High frequency keywords included kidney yang deficiency syndrome,metabolomics,animal models,TCM syndrome types,coronary heart disease,lung qi deficiency syndrome,spleen qi deficiency syndrome,liver depression and spleen deficiency syndrome,etc;Keyword clustering covered aspects such as biomolecules and metabolism,TCM syndromes,pathology,disease models,and animal research.Conclusion Research in the field of the essence of TCM syndromes is gradually receiving more attention.Exploring the essence of TCM syndromes at the molecular level through techniques such as genomics,transcriptomics,metabolomics and proteomics is a research hotspot and trend in this field.
6.Nutritional status and influencing factors in patients undergoing preventive ileostomy
Ruihua LI ; Li ZHEN ; Mulan ZHU ; Xinmei YE ; Fang QIN ; Xingxing ZHANG ; Meiyan LIN ; Guoxin LI
Chinese Journal of Nursing 2025;60(4):396-403
Objective To assess the nutritional status of patients undergoing preventive ileostomy and identify the factors that influence the status,thereby providing guidance for medical staff to formulate nutritional intervention strategies.Methods Convenient sampling was used to select 239 patients undergoing preventive ileostomy who were attending follow-up visits or hospitalized while awaiting stoma closure at 4 tertiary hospitals in Guangzhou from November 2023 to July 2024.Data was collected by a general information questionnaire and the Patient-Generated Subjective Global Assessment tool.Factors influencing nutritional status were analyzed by multivariable ordinal Logistic regression.Results Of the 239 patients,227 provided valid responses.The nutritional status was categorized as follows:64 patients(28.19%)had good nutrition or were at risk of malnutrition;104(45.81%)exhibited moderate malnutrition;59(25.99%)had severe malnutrition.Multivariable ordinal Logistic regression analysis revealed that preoperative cumulative chemotherapy cycles,postoperative duration,age,current dietaiy type,use of oral nutritional supplements(ONS),enterostomy-related complications,and stoma self-care ability were significant predictors of nutritional status(P<0.05).Conclusion Patients undergoing preventive ileostomy are at a high risk of moderate to severe malnutrition and ONS provided to patients did not result in a meaningful improvement in their nutritional health.Specifically,those patients with a higher number of cumulative preoperative chemotherapy cycles,shorter postoperative recovery time,aged ≥ 65 years,liquid diet or semi-liquid diet,experiencing enterostomy-related complications,or poor stoma self-care ability,are particularly vulnerable to malnutrition.These findings underscore the need for medical staff to formulate intervention strategies based on these factors to improve nutritional status of patients undergoing preventive ileostomy.
7.Analysis of influencing factors for gastroesophageal reflux disease after laparoscopic Heller-Dor surgery for esophageal achalasia
Xuemei GUAN ; Fengru ZHANG ; Lihua DU ; Bo ZHANG ; Meiyan GAO ; Rongsheng ZHANG
Chinese Journal of Digestive Surgery 2025;24(10):1318-1325
Objective:To investigate the influencing factors for gastroesophageal reflux disease (GERD) after laparoscopic Heller-Dor surgery for esophageal achalasia.Methods:The retrospective case-control study was conducted. The clinical data of 210 patients with esophageal achalasia who were admitted to Shanxi Provincial Cancer Hospital from January 2021 to December 2023 were collected. There were 119 males and 91 females, aged (47±12)years. All patients underwent laparoscopic Heller-Dor surgery. Observation indicators: (1) surgical situations; (2) follow-up; (3) influencing factors for GERD after laparoscopic Heller-Dor surgery; (4) development and evaluation of a predictive model for GERD after laparoscopic Heller-Dor surgery. Univariate and multivariate analyses were performed using stepwise Logistic regression. Results of multivariate analysis were used to construct a nomogram in predicting GERD. The predictive performance was assessed using the area under the receiver operating characteristic curve. The calibration curve was used to evaluate the accuracy of the model, and the decision curve was used to assess the overall net benefit of the model.Results:(1) Surgical situations. All 210 patients underwent laparoscopic Heller-Dor surgery. The operation time was (128±31)minutes, volume of intraoperative blood loss was (25±9)mL, and length of lower esophageal sphincter (LES) myotomy was (5±3)cm. The length of low esophageal myotomy >6 cm was performed in 49 patients, and length of gastric fundus myotomy >2 cm was performed in 58 patients. Intraoperative mucosal perforation occurred to 3 patients and was repaired intraoperatively. One patient required conversion to open surgery. Postoperative complications occurred in 18 patients. The duration of postoperative hospital stay was (4.3±2.4)days. (2) Follow-up. All 210 patients were followed up for 4(range,7-33)months after surgery. During follow-up, 32 pati-ents had GERD, including 17 cases presenting dysphagia and 25 cases presenting acid regurgitation and heartburn (the same patient may have two symptoms). There were 29 cases with body mass index (BMI) >28 kg/m2. Symptom severity scores of 210 patients showed heartburn of 0.6(range, 0-3.0), reflux of 0.7(range, 0-3.0), chest pain of 0.4(range, 0-2.0), cough and hoarseness of 0.5(range, 0-2.0), nausea and vomiting 0.3(range, 0-2.0), dysphagia 0.8(range, 0-3.0). The LES pressure was (15±8)mmHg (1 mmHg=0.133 kPa), LES relaxation rate was 81%±13.0%, and integrated relaxation pressure was (9±6)mmHg. Esophageal manometry classification showed type Ⅰ, Ⅱ, and Ⅲ in 0, 8, and 0 patients, respectively. There were 208 patients achieved symptom relief after drug or symptomatic treatment. Only two patients with severe symptoms were unresponsive to medication and subsequently underwent surgery at another hospital, with symptoms improving postoperatively. (3) Influen-cing factors for GERD after laparoscopic Heller-Dor surgery. Results of multivariate analysis showed that male, smoking history, length of lower esophageal myotomy >6 cm, and postoperative BMI >28 kg/m2 were independent risk factors for GERD after laparoscopic Heller-Dor surgery ( odds ratio=4.02, 6.34, 5.41, 7.38, 95% confidence interval as 1.50-10.78, 3.31-12.31, 1.77-13.47, 2.80-15.42, P<0.05). (4) Development and evaluation of a predictive model for GERD after laparoscopic Heller-Dor surgery. A predictive nomogram model for GERD was constructed based on the results of multivariate analysis. The receiver operating characteristic curve of predictive nomogram model for GERD had an area under curve of 0.91 (95% confidence interval as 0.82-0.97), demonstrating good discrimination. The calibration curve showed good agreement between predicted and observed probabilities, with a mean absolute error of 0.033. The decision curve demonstrated that within a threshold probability range of 0.2-0.8, the predictive model had greater net benefit than "treat-all" or "treat-none" strategies, indicating clinical utility of this model in clinical decision. Conclusions:Male, smoking history, length of lower esophageal myotomy >6 cm, and postoperative BMI >28 kg/m2 are independent risk factors for GERD after laparoscopic Heller-Dor surgery for esophageal achalasia. The predictive model for GERD after laparoscopic Heller-Dor surgery based on these factors shows strong predictive accuracy.
8.Histomorphology of Colorectal Superficially Serrated Adenoma and the Role of RSPO2 and RSPO3 in its Carcinogenic Mechanism
Suming GAO ; Lin WANG ; Meiyan LIANG ; Zhenhua ZHANG ; Xiaosai CHEN ; Li LI
Chinese Journal of Gastroenterology 2025;30(1):32-37
Background:Colorectal cancer(CRC)is a major cause of cancer death worldwide,and about 30%to 35%of CRC arises from the serrated pathway.Aims:To analyze the clinicopathological and histomorphological characteristics of colorectal superficially serrated adenoma(SuSA),and to investigate the malignant transformation potential of SuSA and further elucidate the role of RSPO2 and RSPO3 in its carcinogenic mechanism.Methods:A total of 169 serrated colorectal lesions confirmed pathologically and fulfilling the inclusion criteria were collected from Shanxi Bethune Hospital from February 2019 to May 2023.Among them,there were 84 cases of SuSA,23 sessile serrated lesions(SSL),32 traditional serrated adenomas(TSA),and 30 hyperplastic polyps(HP).Thirty-nine cases of tubular adenoma(TA),32 CRC,and 33 normal colorectal mucosal tissues were served as controls.The clinicopathological and histomorphological parameters were collected and recorded.Immunohistochemical staining was used to detect the protein expressions of RSPO2,RSPO3,p53,MLH1 and β-catenin.Results:Patients with SuSA were male predominance,with a mean age of 51.89 years.The average diameter of the lesions was 0.20 cm,predominantly located in the left colon and rectum,and frequently complicated with other polyps/adenomas.The histomorphological features of SuSA were as follows:the glandular necks and crypt bases exhibited straight tubular structure with low-grade dysplasia;the superficial layer demonstrated a serrated architecture,with or without dysplasia,and contained a variable number of goblet cells.Immunohistochemically,there were no statistically significant differences in RSPO2,RSPO3,and p53 expressions between SuSA and TSA(all P>0.05).A strong positive correlation was observed between RSPO2 and RSPO3 in colorectal lesions,excluding HP.Expressions of MLH1 and β-catenin showed no statistically significant differences between SuSA and other colorectal lesions(all P>0.05).Conclusions:SuSAs are more common in males,occur mostly in the left colon and rectum,and are often associated with other polyps/adenomas.They might be precursors of KRAS-mutated TSA and microsatellite stable CRC with high malignant potential.RSPO2 and RSPO3 might play an important role in the carcinogenesis of SuSA.
9.Role of STING/ACSL4 signaling pathway in alleviation of oxygen-glucose deprivation and restoration-induced ferroptosis in renal tubular epithelial cells
Jieyu MIN ; Liunian YING ; Meiyan LIU ; Jingfeng CHEN ; Qing ZHANG ; Yi ZHONG
Chinese Journal of Anesthesiology 2025;45(5):603-610
Objective:To evaluate the role of interferon gene stimulator/long-chain ester acyl-CoA synthetase 4 (STING/ACSL4) signaling pathway in alleviation of oxygen-glucose deprivation and restoration (OGD/R)-induced ferroptosis in renal tubular epithelial cells.Methods:The close juxial tubule epithelial cells of human renal cortex were selected and divided into 9 groups ( n=78 each) using a random number table method: control group (C group ), OGD/R group, OGD/R + 25 μmol/L ciprofol group (HC25 group), OGD/R + 50 μmol/L ciprofol group (HC50 group), OGD/R + 100 μmol/L ciprofol group (HC100 group), virus control (NC) group, OGD/R + NC group, OGD/R + ciprofol + NC group (OGD/R+ Cip+ NC group), and OGD/R + ciprofol + STING overexpression lentivirus group (OGD/R+ Cip+ OE-STING group). The OGD/R model was developed by subjecting the cells to O 2-glucose deprivation (OGD) for 4 h followed by restoration of O 2-glucose supply for 20 h. Ciprofol at a final concentration of 25, 50 and 100 μmol/L was added to the medium during OGD/R in HC25, HC50, and HC100 groups, respectively. The cells were subjected to conventional culture after infection with the control virus of the STING overexpression lentivirus in NC group. The OGD/R model was developed after the cells were infected with control virus in OGD/R+ NC group. In OGD/R+ Cip+ NC group and OGD/R+ Cip+ OE-STING group, the cells were infected with control virus and STING overexpression lentivirus, respectively, and ciprofol 50 μmol/L was added to the medium during OGD/R. Cell damage parameters included the cell viability and activity of lactic dehydrogenase (LDH) in supernatant. The oxidative stress parameters included the activity of reactive oxygen species (ROS) and contents of malondialdehyde (MDA) and glutathione (GSH). Mitochondrial damage parameters included the mitochondrial area and branch length, content of mitochondrial 8-hydroxydeoxyguanosine (8-OHdG) in mitochondrial DNA (mtDNA), and DNA expression of nicotinamide adenine dinucleotide dehydrogenase 1 and 2 (mtND1, mtND2) and cytochrome oxidase (COX-1). The ferroptosis parameters included Fe 2+ content and expression of STING, ACSL4, nuclear factor-κB (NF-κB), cyclic GMP-AMP synthase (cGAS), and glutathione peroxidase 4 (GPX4) protein and mRNA. Results:Compared with group C, the activity of LDH in the supernatant was significantly increased, the cell viability was decreased, the ROS activity, MDA content, and Fe 2+ content were increased, the GSH content was decreased, the expression of ACSL4, cGAS, STING, NF-κB protein and mRNA was up-regulated, the expression of GPX4 protein and mRNA was down-regulated, the content of 8-OHdG in mtDNA was increased, the DNA expression of cytoplasmic mtND1, mtND2 and COX-1 was up-regulated, and the mitochondrial area and branch length were increased in group OGD/R ( P<0.05). Compared with OGD/R group, the cell viability and GSH content were significantly increased, the MDA content and Fe 2+ content were decreased, the expression of ACSL4, cGAS, STING, NF-κB protein and mRNA was down-regulated, the expression of GPX4 protein and mRNA was up-regulated, the content of 8-OHdG in mtDNA was decreased, and the DNA expression of cytoplasmic mtND1, mtND2 and COX-1 was up-regulated in HC50 group ( P<0.05). Compared with OGD/R+ Cip+ NC group, the cell viability was significantly decreased, the ROS activity was increased, the expression of ACSL4, cGAS and NF-κB protein and mRNA was up-regulated, the expression of GPX4 protein and mRNA was down-regulated, and the DNA expression of cytoplasmic mtND1, mtND2 and COX-1 was up-regulated in OGD/R+ Cip+ OE-STING group ( P<0.05). Conclusions:Ciprofol may exert cytoprotective effects by alleviating ferroptosis during OGD/R in renal tubular epithelial cells by inhibiting STING/ACSL4 signaling pathway.
10.Role of TBK1/RIPK1 signaling pathway in postoperative cognitive dysfunction in aged mice
Yuhan ZHANG ; Yu QI ; Meiyan ZHOU ; Teng LI ; Jiyan XU ; Liwei WANG
Chinese Journal of Anesthesiology 2025;45(10):1280-1285
Objective:To evaluate the role of the TANK-binding kinase 1 (TBK1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a table of random numbers: control group (group C), POCD group, dimethyl sulfoxide group, GSK group and GSK+ Nec-1 group. A mouse model of POCD was established by the closed reduction internal fixation of the left tibial fracture in anesthetized animals. Dimethyl sulfoxide, TBK1 inhibitor GSK8612 and RIPK1 inhibitor Nec-1 (0.5 μl/side) were stereotactically injected into the hippocampal CA1 region at 30 min before operation. Cognitive function was assessed using the contextual fear conditioning test before operation and at 3 days after operation. The mice were then anesthetized and sacrificed, and the hippocampal tissues were obtained for determination of the expression of TBK1, RIPK1, interleukin-lbeta (IL-1β), tumor necrosis factor-alpha (TNF-α), activator protein 1 (AP-1) and Nestin (by Western blot), the expression of Bcl-2, Bax and caspase-3 mRNA (by fluorescent quantitative real-time polymerase chain reaction) and for examination of TBK1/RIPK1 molecular interactions and neural stem cell proliferation in the hippocampal dentate gyrus (DG) region (by immunofluorescent staining). Results:Compared with C group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, RIPK1, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in POCD group ( P<0.05 or 0.01). Compared with POCD group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in GSK group ( P<0.05 or 0.01). Compared with GSK group, the percentage of freezing time was significantly increased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was down-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was up-regulated, and the proliferation of neural stem cells in the hippocampal DG region was increased in GSK+ Nec-1 group ( P<0.05 or 0.01). Conclusions:The TBK1/RIPK1 signaling pathway is involved in the pathogenesis of POCD in aged mice.

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