OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

OBJECTIVE To analyze the chemical constituents and absorbed prototype components in blood of Zhenyang jiuxin decoction， and explore its potential active substances in the treatment of chronic heart failure （CHF）. METHODS SD rats were divided into a blank group （distilled water） and administration groups with blood collection at 0， 15， 30 and 60 min after dosing （14.96 g/kg calculated by crude drug）， with 2 rats in each group. Intragastric administration was conducted once every 12 hours for 3 consecutive days. After the last administration， rat blood was collected to prepare drug-containing serum. UPLC-Q-Exactive Orbitrap HRMS combined with the Global Natural Products Social Molecular Networking technology was adopted to identify the chemical constituents of Zhenyang jiuxin decoction and the absorbed prototype components in blood in drug-containing serum. Moreover， network pharmacology， molecular docking and molecular dynamics simulation were used to predict the potential active components and action targets for CHF treatment. RESULTS A total of 116 chemical constituents were identified from Zhenyang jiuxin decoction， including flavonoids （29 species）， terpenoids （26 species）， saponins （22 species） and other compounds. Twenty absorbed prototype components in blood were detected in drug-containing serum， including icariin， ginsenoside Rg 1 and atractylenolide Ⅰ. Six key active components （icariin， ginsenoside Rg 1 ， atractylenolide Ⅰ， hexadecanamide， etc.） and six core k ey targets such as glycogen synthase kinase-3β （GSK-3β）， amyloid precursor protein （APP） and epidermal growth factor receptor （EGFR） were screened out via network pharmacology. Molecular docking results showed that all key active components had favorable binding activity with core targets； among them， icariin had the strongest binding capacity to APP. Molecular dynamics simulation verified that the complex formed by icariin and APP possessed excellent stability. CONCLUSIONS The potential active substances of Zhenyang jiuxin decoction against CHF are icariin， ginsenoside Rg₁， atractylenolide Ⅰ and other ingredients， which act on APP， EGFR， GSK-3β and other targets. APP may serve as one of the important action targets of icariin.

Objective:To evaluate the feasibility of transjugular transcatheter tricuspid valve replacement (TTVR) using the LuX-Valve Plus system (Ningbo Jenscare Scientific, China) for the treatment of severe tricuspid regurgitation in real-world clinical settings.Methods:This prospective study enrolled 81 patients with severe ricuspid regurgitation (≥3+) who underwent TTVR with the LuX-Valve Plus system at the Department of Cardiology, West China Hospital of Sichuan University between May 2022 and March 2024. Among them, 44 patients were from a compassionate-use study, and 37 were from two premarket clinical trials. Baseline clinical data, preprocedural imaging, procedural outcomes, and postprocedural follow-up data were collected. The primary endpoint events included device success, procedural success, and 30 d composite adverse events.Results:The age of the cohort was (74.5±7.8) years, with 54 females (67%). Device success and procedural success rates were both 90% (73/81). Post-procedural tricuspid regurgitation improved, with a 6% (5/81) incidence of moderate-to-severe paravalvular leakage. The rate of permanent pacemaker implantation was 12% (10/81), of which 5% (4/81) had pre-existing indications for pacemaker implantation. Major bleeding events occurred in 10% (8/81) of patients, and the 30 d composite endpoint rate was 25% (20/81).Conclusion:TTVR using the LuX-Valve Plus system demonstrates promising feasibility for high-risk surgical patients with severe tricuspid regurgitation, effectively reducing or eliminating regurgitation with acceptable safety. However, challenges remain in reducing risks of major adverse events, including permanent pacemaker implantation and severe bleeding.

Objective:To evaluate the feasibility of transjugular transcatheter tricuspid valve replacement (TTVR) using the LuX-Valve Plus system (Ningbo Jenscare Scientific, China) for the treatment of severe tricuspid regurgitation in real-world clinical settings.Methods:This prospective study enrolled 81 patients with severe ricuspid regurgitation (≥3+) who underwent TTVR with the LuX-Valve Plus system at the Department of Cardiology, West China Hospital of Sichuan University between May 2022 and March 2024. Among them, 44 patients were from a compassionate-use study, and 37 were from two premarket clinical trials. Baseline clinical data, preprocedural imaging, procedural outcomes, and postprocedural follow-up data were collected. The primary endpoint events included device success, procedural success, and 30 d composite adverse events.Results:The age of the cohort was (74.5±7.8) years, with 54 females (67%). Device success and procedural success rates were both 90% (73/81). Post-procedural tricuspid regurgitation improved, with a 6% (5/81) incidence of moderate-to-severe paravalvular leakage. The rate of permanent pacemaker implantation was 12% (10/81), of which 5% (4/81) had pre-existing indications for pacemaker implantation. Major bleeding events occurred in 10% (8/81) of patients, and the 30 d composite endpoint rate was 25% (20/81).Conclusion:TTVR using the LuX-Valve Plus system demonstrates promising feasibility for high-risk surgical patients with severe tricuspid regurgitation, effectively reducing or eliminating regurgitation with acceptable safety. However, challenges remain in reducing risks of major adverse events, including permanent pacemaker implantation and severe bleeding.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Purpose: This study aimed to investigate the effect of the N6-methyladenosine (m6A) dependent ferroptosis on cisplatininduced Sertoli cell injury. Materials and Methods: A cisplatin exposure mouse model was established by intraperitoneal injection of cisplatin in our study. TM4 cell lines was used for in vitro study. Ferroptosis was detected according to metabolomic analysis and a series of assays, including malondialdehyde, glutathione, and glutathione disulfide concentration detection, 2′,7′-dichlorodihydrofluorescein diacetate and BODIPY 581/591 C11 probe detection, and transmission electron microscope imaging. Key ferroptosis-related genes were identified via transcriptomic analysis, western blot and immunohistochemistry. The m6A modification was demonstrated via m6A RNA immunoprecipitation and luciferase reporter assays. Immune cell infiltration was detected by mass cytometry, and verified by flow cytometry and immunofluorescence. Results: Ferroptosis, but not other types of programmed cell death, is a significant phenomenon in cisplatin-induced testis damage and Sertoli cell loss. Ferroptosis induced by cisplatin in Sertoli cell/TM4 cell is GPX4 independent but is regulated by SLC7A11 and ALOX12. Both SLC7A11 and ALOX12 are regulated via m6A dependent manner by METTL3. Furthermore, overexpressed ALOX12-12HETE pathway may result in macrophage polarization and inflammatory response in cisplatin exposure testis. Conclusions Cisplatin-induced Sertoli cell injury via ferroptosis and promoted ferroptosis in an m6A dependent manner. m6A modification of both SLC7A11 and ALOX12 mRNA could result in ferroptosis in our in vitro model. Further, overexpressed ALOX12 can cause more production of 12-HETE, which may be responsible for testis inflammation caused by cisplatin.

Objective:To explore the efficacy of O-arm navigation system-assisted upper cervical pedicle screw internal fixation in the treatment of traumatic atlantoaxial instability.Methods:A retrospective cohort study was conducted to analyze the clinical data of 61 patients with atlantoaxial instability admitted to Affiliated Honghui Hospital of Xi′an Jiaotong University from January 2021 to June 2022, including 34 males and 27 females, aged 20-77 years [(50.2±13.1)years]. A total of 38 patients were treated with unarmed screw placement (unarmed group), and 23 with O-arm navigation system-assisted screw placement (navigation group). The unarmed group was divided into experienced group ( n=20) and unexperienced group ( n=18) based on the surgeons′ experience (whether they had 20 years or longer experience of spinal surgery and performed more than 100 atlantoaxial surgeries independently). The screw placement and surgical time of each group was recorded. The cervical CT scan was conducted at 7 days after surgery to evaluate the satisfaction rate of pedicle screw placement and cortical penetration rate according to Neo grading criteria. The cervical nerve function of the patients before, at 7 days after surgery and at the last follow-up was evaluated using the Japanese Orthopedic Association (JOA) score and the Neck Disability Index (NDI). The occurrence of complications was observed. Results:All patients were followed up for 9-25 months [(16.3±4.2)months]. There were no statistically significant differences in the screw placement and surgical time between the navigation group and the unarmed group (all P>0.05). The screw placement time of the navigation group was (41.0±7.8)minutes, longer than that of the experienced group [(23.6±6.8)minutes] ( P<0.01) and shorter than that of the unexperienced group [(50.1±10.1)minutes] ( P<0.05). The surgical time of the navigation group was (101.9±9.9)minutes, which was longer than that of the experienced group [(67.6±8.3)minutes] ( P<0.01) and shorter than that of the unexperienced group [(126.1±16.4)minutes] ( P<0.01). The satisfaction rate of pedicle screw placement and cortical penetration rate of the navigation group were 98.9% and 4.3%, respectively, which were better than those of the unarmed group (94.1% and 17.8%), the experienced group (96.2% and 13.8%), and the unexperienced group (91.7% and 22.2%) ( P<0.05 or 0.01). There was no statistically significant difference in JOA score or NDI before, at 7 days after surgery or at the last follow-up between the navigation group and the unarmed group, and no difference between the navigation group and the experienced group or the unexperienced group (all P>0.05). No complications such as spinal cord nervous or vascular injuries were observed during surgery in the navigation group or the unarmed group. Conclusions:Compared with the unarmed screw placement, O-arm navigation system-assisted upper cervical pedicle screw internal fixation shows no significant difference in screw placement time, surgical time, and postoperative neurological function status in the treatment of traumatic atlantoaxial instability, but has a higher accuracy in screw placement. Compared with the experienced surgeons′ unarmed screw placement, the technique also has higher screw placement accuracy but longer screw placement time and surgical time. Whereas in comparison with unexperienced surgeons′ unarmed screw placement, the technique can not only significantly improve its screw placement accuracy, while shortening screw placement time and surgical time so as to improve the surgical safety.