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 trends and outcomes for heart transplantation (HT) in elderly recipients and further examine the related risk factors.Methods:Between June 2004 and December 2021, retrospective review was conducted for the relevant clinical data and age distribution of 1044 HT recipients aged ≥18 year at Fuwai Hospital. The study population was assigned into two groups of elder (≥60 year, n=877) and non-elder (<60 year, n=157). Subgroup analysis was made between recipients aged <65 year (n=107) and those aged ≥ 65 year (n=50) in elder group. Baseline demographic profiles, clinical data, in-hospital and one-year post-transplant mortality and long-term survival were compared between two groups. Then a further comparison of long-term survival was conducted among the groups of non-elder, elder aged <65 year and elder aged ≥65 year. Cox proportional risk regression and multivariate Logistic regression models were utilized for examining the relevant risk factors for cumulative survival rate and short-term mortality. Kaplan-Meier analysis was employed for plotting survival curves and Log-rank test for comparison. Multivariate Cox proportional risk regression model was utilized for examining the relevant risk factors for cumulative survival rate and multivariate Logistic regression model for analyzing the relevant risk factors for short-term mortality. After adjusting for other confounding factors, the impact of recipient age on survival post-HT was determined.Results:The number of elderly HT recipients spiked annually at our center while average age of adult recipients and average age of elderly recipients have remained relatively constant. The median follow-up period was 6.5 years. Regarding baseline data, statistically significant differences existed in ratio of males [84.7%(113/157) vs 77.5%(687/877)], hypertension history [20.4%(32/157) vs 8.9%(79/877)], smoking history [47.1%(74/157) vs 36.1%(320/877)], diabetic history [33.8%(53/157) vs 14.7%(130/877)], preoperative ICD/CRT/CRT-D implantation [28.0%(44/157) vs 18.0%(160/877)], value of creatinine [(105.3±25.3) vs (96.8±35.0) μmol/L], IMPACT score [(6.9±2.4) vs (4.2±2.9) point], serum total bilirubin [19.7(13.6, 30.3) vs 23.7(15.8, 36.8) μmol/L], mean pulmonary arterial pressure [(26.0±10.3) vs (29.7±11.0) mmHg (1 mmHg=0.133 kPa)] and ischemic duration [(274.7±105.6) vs (296.0±120.4) min] (all P<0.05). No significant inter-group difference existed in in-hospital mortality [4.5%(7/157) vs 4.7%(42/887)] or 1-year mortality [5.7%(9/157) vs 6.5%(58/887)] ( P=0.88, P=0.70); in-hospital mortality and 1-year postoperative mortality of recipients aged ≥65 years 10.0%(5/50) and 14.0%(7/50) were both higher than those aged <65 year [1.9%(2/107), 1.9%(2/107)]. The differences were both statistically significant ( P=0.02, P<0.01). Kaplan-Meier survival analysis indicated that long-term survival rate was lower in elder group than that in non-elder group and the difference was statistically significant ( P=0.046). Long-term survival rate of elders aged ≥65 year was lower than that of non-elders aged <65 year and the difference was statistically significant ( P<0.01). Regression analysis indicated that age of recipient ≥65 year, preoperative creatinine ≥133 μmol/L, preoperative total bilirubin ≥25.65 μmol/L and preoperative support of extracorporeal membrane oxygenation (ECMO) were independent risk factors for short/long-term mortality post-HT. Conclusion:Although long-term prognosis of elderly recipients is slightly worse than that of non-elderly ones, in-hospital mortality and one-year postoperative mortality are similar between two groups. For elderly recipients with fewer comorbidities and better preoperative status, they should not be excluded from HT based solely upon age. The long-term prognosis of recipients aged ≥65 year remains poor and HT decisions should be made carefully.

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 compare the clinical efficacies of O-arm combined with CT three-dimensional navigation system assisted screw placement versus manual screw placement in treating lower cervical fracture and dislocation.Methods:A retrospective cohort study was used to analyze the clinical data of 41 patients with lower cervical fracture and dislocation, who were treated in Honghui Hospital, Xi′an Jiaotong University from May 2021 to February 2022. The patients included 26 males and 15 females, aged 31.5-48.6 years [(41.5±15.0)years]. The injured segments were C 3 in 3 patients, C 4 in 12, C 5 in 13, C 6 in 10 and C 7 in 3. Nineteen patients were treated with cervical pedicle screws by O-shaped arm combined with CT three-dimensional navigation system (navigation group, 76 screws) and 22 by bare hands (traditional group, 88 screws). The total operation time, effective operation time, single nail placement time, single screw correction times, screw distance from anterior cortex, intraoperative blood loss, intraoperative fluoroscopic radiation dose, incision length and length of hospital stay were compared between the two groups, and the height of intervertebral space, Cobb angle, interbody slip distance and American Spinal injury Association (ASIA) grade were compared before operation and at 3 days after operation. Visual analogue score (VAS), Japanese Orthopedic Association (JOA) score, and neck dysfunction index (NDI) were evaluated before operation, at 3 days, 3 months after operation and at the last follow-up. Accuracy of screw placement and incidence of complications (adjacent facet joint invasion, infection, screw loosening) were detected as well. Results:All the patients were followed up for 11.1-13.9 months [(12.5±1.4)months]. The total operation time, intraoperative blood loss, intraoperative fluoroscopic radiation dose and incision length in the navigation group were more or longer than those in the traditional group (all P<0.05). The effective operation time, single nail placement time, single nail correction times and screw distance from anterior cortex in the navigation group were markedly less or smaller than those in the traditional group (all P<0.05). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). There were significant improvements in the height of intervertebral space, Cobb angle and interbody slip distance between the two groups at 3 days after operation (all P<0.05). There was no significant difference in the height of intervertebral space, Cobb angle, interbody slip distance or ASIA grade between the two groups before operation or at 3 days after operation (all P>0.05). Compared with pre-operation, the VAS, JOA score and NDI were significantly improved in both groups at 3 days, 3 months after operation and at the last follow-up (all P<0.05), with further improvement with time. There was no significant difference in VAS between the two groups before operation or at 3 months after operation (all P>0.05), but it was markedly lower in the navigation group compared with the traditional group at 3 days after operation and at the last follow-up (all P<0.05). There were no significant differences in JOA score or NDI between the two groups before operation or at 3 days and 3 months after operation (all P>0.05), but both were lower in the navigation group compared with the traditional group at the last follow-up (all P<0.05). The accuracies of placement of grade 0 and grade 0+1 screws were 92.0% (70/76) and 96.6% (73/76) in the navigation group, respectively, which were markedly higher than 88.7% (78/88) and 93.5% (82/88) in the traditional group (all P<0.05). The rates of adjacent facet joint invasion of A, B, and C degrees were 71.2% (54/76), 28.8% (22/76) and 0% (0/76) in the navigation group, respectively, while the invasion rates were 60.5% (53/88), 32.3% (28/88) and 7.3% (7/88) in the traditional group ( P<0.05). No screw loosening was noted in the navigation group, but the screw loosening rate was 9.1% (8/88) in the traditional group ( P<0.01). Conclusion:Compared with manual screw placement, O-arm combined with CT three-dimensional navigation system assisted screw placement for lower cervical fracture and dislocation has the advantages of shorter effective operation time, quicker screw placement, stronger screw holding force, better cervical stability, slighter postoperative pain, higher screw placement accuracy, and lower facet joint invasion and screw loosening rates.

Objective:To explore the morbidity and risk factors of de novo malignancy after heart transplantation (HT).Methods:From June 2004 to August 2021, 995 patients undergoing HT were selected and followed up.The epidemiological characteristics, the morbidity of de novo malignancy (DNM) and its risk factors were examined.Kaplan-Meier survival analysis was performed for calculating the cumulative incidence and mortality of DNM.Log rank test was utilized for comparing the survival rate of each subgroup.Cox regression model was employed for examining the relationship between the included factors and the endpoint of DNM.Results:The median follow-up period was 6.36(3.64, 10.18) years.Thirty-six patients (3.6%) developed DNM during follow-up.Lung cancer accounted for 22.2%(8/36) of DNM while digestive system tumors accounted for 38.9% (including gastric cancer 6/36, 16.7%; liver cancer 3/36, 8.3%; colon cancer 2/36, 5.6%). The cumulative morbidity of DNM at Year 1/5/10/15 post-HT was 0.1%, 2.3%, 4.9% and 7.6% respectively.The median survival time of DNM recipients was 83.32 months.The mean survival time was significantly lower than those without DNM[(115.32±13.12) vs.(194.22±2.58), P<0.001]. The mortality of DNM recipients was around 6.57 folds higher ( HR=6.57, 95% CI: 4.06-10.64, P<0.01). Age was an independent risk factor for an occurrence of DNM.Hypertension and diabetes were also correlated with DNM. Conclusions:DNM after HT is associated with shorter survival time.And age is an independent risk factor for DNM after HT.

Plant-derived exosome-like nanoparticles(PELNs) are a class of membranous vesicles with diameters approximately ranging from 30 to 300 nm, isolated from plant tissues. They contain components such as proteins, lipids, and nucleic acids. PELNs play an important role in the metabolism of plant substances and immune defense, and can also cross-regulate the physiological activities of fungi and animal cells, showing significant potential applications. In recent years, research on PELNs has significantly increased, highlighting three main issues:(1) the mixed sources of plant materials for PELNs;(2) the lack of a unified system for isolating and characterizing PELNs;(3) the urgent need to elucidate the molecular mechanisms underlying the cross-regulation of biological functions by PELNs. This article focused on these concerns. It began by summarizing the biological origin and composition of PELNs, discussing the techniques for isolating and characterizing PELNs, and analyzing their biomedical applications and potential future research directions., aiming to promote the establishment of standardized research protocols for PELNs and provide theoretical references for in-depth exploration of the mechanisms underlying PELNs' cross-regulatory effects.
Animals ; Exosomes/metabolism* ; Proteins/metabolism* ; Plants/metabolism* ; Nucleic Acids ; Nanoparticles

Objective:To study the efficacy, feasibility and safety of transjugular intrahepatic portosystemic shunt (TIPS) in treatment of recurrent portal hypertension after splenectomy and devascularization in patients presenting with upper gastrointestinal bleeding.Methods:Cirrhotic patients with recurrent portal hypertension after splenectomy and devascularization and presenting with upper gastrointestinal bleeding from August 2015 to December 2020 were studied. Thirty-nine patients were included in this study. There were 24 males and 15 females, with age of (51.56±9.08) years old. These patients were treated with TIPS by using the Viabahn stent. Intraoperative portal vein pressure, success operative rate, hemostasis rate after surgery, changes in hematological indicators and postoperative efficacy and complication rate were studied.Results:Thirty-eight of 39 patients successfully underwent TIPS shunt and 1 patient failed because of portal vein spongiosis. The success rate was 97.44%(38/39). Thirty-three patients underwent TIPS and variceal vein embolization, while 5 patients were treated with TIPS alone. Thirty-nine Viabahn stents with a diameter of 8 mm were implanted in 38 patients, of which 5 patients had the stent expanded to its nominal diameter of 8 mm. The remaining 33 patients (86.84%) had a shunt with a diameter of 6 mm. The hemostasis rate of postoperative gastrointestinal bleeding was 97.37% (37/38). The portal vein pressure and portal venous pressure gradient decreased from (31.28±6.24), (20.61±5.14) mmHg (1 mmHg=0.133 kPa) to (19.58±4.69), (9.24±3.07) mmHg respectively, the differences were significant (all P<0.001). All patients were followed-up for 3 to 36 months, with a median follow-up of 12 months. The postoperative rebleeding rate was 6.90% (2/29). The incidence of hepatic encephalopathy was 13.79% (4/29), and the incidence of shunt disorder was 13.79% (4/29). Conclusion:TIPS was safe, effective and feasible in treating patients with recurrent portal hypertension after splenectomy and devascularization presenting with upper gastrointestinal bleeding. Most patients obtained good clinical outcomes with a 6 mm diameter shunt.