Hemolysis is one of the main complications associated with the use of ventricular assist devices. The primary factors influencing hemolysis include the shear stress and exposure time experienced by red blood cells. In addition, factors such as local negative pressure and temperature may also impact hemolysis. The different combinations of hemolysis prediction models and their empirical constants lead to significant variations in prediction results; compared to the power-law model, the OPO model better accounts for the complexity of turbulence. In terms of improving hemolytic performance, research has primarily focused on optimizing blood pump structures, such as adjustments to pump gaps, impellers, and guide vanes. A small number of scholars have studied hemolytic performance through control modes of blood pump speed and the selection of blood-compatible materials. This paper reviews the main factors influencing hemolysis, prediction methods, and improvement strategies for rotary blood pumps, which are currently the most widely used. It also discusses the limitations in current hemolysis research and provides an outlook on future research directions.

Intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has become the primary treatment for macular edema associated with retinal vascular disease such as diabetic retinopathy and retinal vein occlusion, but there are limitations such as variable treatment efficacy and insufficient durability of therapeutic effects. As the first bispecific antibody applied in ophthalmic treatment, Faricimab achieves favorable outcomes by simultaneously targeting both VEGF-A and angiopoietin-2(Ang-2)pathways. Based on evidence from recent clinical trials and real-world studies, this article reviews the research progress on Faricimab for the treatment of diabetic macular edema(DME), retinal vein occlusion-associated macular edema(RVO-ME)and refractory macular edema compared to the therapeutic effects of other agents. Additionally, based on Faricimab's safety characteristics and future potential, its therapeutic prospects for macular edema associated with retinal vascular diseases are discussed. This review aims to provide evidence-based references for optimizing clinical treatment strategies, thereby contributing to mitigating the risk of vision loss due to macular edema.

Objective:To investigate the radiation field distribution characteristics in a 9 MeV electron FLASH (e-FLASH) linear accelerator treatment room.Methods:The Geant4 Monte Carlo program was employed for physical simulating of the radiation field distribution inside and outside the treatment room under a single-beam delivery condition with a total dose of 50 Gy at the reference point and a dose rate of 250 Gy/s. High-sensitivity radiation detectors (AT1123) were used to validate the measurements at key points.Results:The dose rate at the reference point was approximately 9×10 11 μSv/h. Due to the scattering and shielding effects, the deviation of the attenuation rate from the inverse-square law was observed and the isodose lines exhibited spatial drift. Measured dose rates at key points showed good agreement with the simulation result, with a maximum deviation within 30%. Conclusions:The complex radiation field distribution can be effectively simulated using Geant4 in an e-FLASH treatment room. This indicated the Geant4 is not only applicable for the shielding calculations in e-FLASH radiotherapy facilities, but also for the design optimization through, reduction of trial-and-error iterations and engineering costs.

BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To investigate the relationship between oxidative stress-related genes and pros-tate cancer(PCa)from a multi-omics perspective using summary-data-based Mendelian randomization(SMR),colocalization analysis,and cellular experiments.Methods:Summary-level data on DNA methylation,gene expression,and circulating proteins were obtained and filtered.The PRACTICAL con-sortium was used as the discovery cohort,with the deCODE database serving as the validation cohort.SMR analysis and heterogeneity in dependent instruments(HEIDI)tests were conducted to assess the association and heterogeneity between oxidative stress-related genes and PCa.Colocalization analysis was performed to determine whether oxidative stress-related genes and PCa shared common causal variants.Final-ly,CCK-8 assays,wound healing assays,and Transwell invasion assays and Western blotting,were con-ducted to examine the effects of oxidative stress-related genes on the biological behavior of the PCa cell line C4-2.Results:Multi-omics analysis identified SCP2 as significantly associated with increased PCa risk across gene methylation,gene expression,and circulating protein levels.GSTP1 showed significant associations at the methylation and protein levels,while LPO was associated at the protein level.At the methylation level,SCP2 sites cg00581603(OR=1.11,95％CI:1.05-1.17)and cg13078931(OR=1.12,95％CI:1.05-1.18)were identified as pathogenic.Among the four methylation sites in GSTP1,only cg05244766(OR=0.89,95％CI:0.84-0.95)was considered protective.At the gene expression level,SCP2(OR=1.05,95％CI:1.02-1.07)was also found to be a pathogenic factor.At the circu-lating protein level,SCP2(OR=2.10,95％CI:1.34-3.29)showed a consistent pathogenic trend.In addition,GSTP1(OR=1.16,95％CI:1.07-1.25)and LPO(OR=1.12,95％CI:1.05-1.19)were significantly associated with increased PCa risk.Further functional assays demonstrated that knock-down of SCP2 significantly reduced the oncogenic phenotype of prostate cancer cells.Conclusion:Through integrated multi-omics analysis and experimental validation,this study confirmed a significant as-sociation between SCP2 and increased PCa risk.These findings enhance our understanding of PCa patho-genesis and provide new potential targets and therapeutic directions for PCa treatment.

Objective:To investigate the radiation field distribution characteristics in a 9 MeV electron FLASH (e-FLASH) linear accelerator treatment room.Methods:The Geant4 Monte Carlo program was employed for physical simulating of the radiation field distribution inside and outside the treatment room under a single-beam delivery condition with a total dose of 50 Gy at the reference point and a dose rate of 250 Gy/s. High-sensitivity radiation detectors (AT1123) were used to validate the measurements at key points.Results:The dose rate at the reference point was approximately 9×10 11 μSv/h. Due to the scattering and shielding effects, the deviation of the attenuation rate from the inverse-square law was observed and the isodose lines exhibited spatial drift. Measured dose rates at key points showed good agreement with the simulation result, with a maximum deviation within 30%. Conclusions:The complex radiation field distribution can be effectively simulated using Geant4 in an e-FLASH treatment room. This indicated the Geant4 is not only applicable for the shielding calculations in e-FLASH radiotherapy facilities, but also for the design optimization through, reduction of trial-and-error iterations and engineering costs.

BACKGROUND:According to different locations of lumbar disc herniation,it can be classified into many types.Among them,patients with intradural sac type lumbar disc herniation have severe clinical symptoms,which greatly affect their quality of life.Therefore,this article studies the risk factors for its onset,and improving the preoperative diagnostic rate is of great significance for the treatment and prevention of this disease.OBJECTIVE:To explore the risk factors for intradural lumbar disc herniation.METHODS:A retrospective analysis was conducted on 15 patients with intradural lumbar disc herniation(herniation group)admitted to three hospitals in Xuzhou city from May 2014 to November 2022.Propensity score matching was used to match patients with lumbar disc herniation who did not protrude into the dura mater in a ratio of 1:4.A total of 59 patients were selected and included in the non-herniation group.Clinical data were observed in the two groups.Univariate and binary logistic regression analysis,multiple linear regression,and PROBIT regression analysis were utilized to identify the relevant risk factors for intradural lumbar disc herniation.RESULTS AND CONCLUSION:(1)The results of univariate analysis showed that the average disease course,proportion of segments,modified Pfiirmann grading,sacral tilt angle,proportion of previous lumbar spine surgery history,and proportion of heavy manual workers,proportion of lumbar spinal stenosis,redundancy of the cauda equina,and ossification of the posterior longitudinal ligament all showed statistical differences in the herniation and non-herniation groups(P＜0.05).(2)Multivariate regression analysis showed that duration of disease,protruding segment,history of lumbar surgery,modified Pfiirmann grading,cauda equina redundancy,and lumbar spinal stenosis were independent risk factors for intradural lumbar disc herniation.(3)Based on the influencing factors,an receiver operating characteristic curve was constructed,with an area under curve of 0.956(95％CI:0.913-0.998),indicating good discrimination.(4)There was a significant correlation between the duration of the disease,the protruded segment,the history of lumbar spine surgery,the modified Pfirmann classification,cauda equina redundancy,lumbar spinal canal stenosis,and the incidence rate of intradural lumbar disc herniation.

Objective:To investigate the relationship between oxidative stress-related genes and pros-tate cancer(PCa)from a multi-omics perspective using summary-data-based Mendelian randomization(SMR),colocalization analysis,and cellular experiments.Methods:Summary-level data on DNA methylation,gene expression,and circulating proteins were obtained and filtered.The PRACTICAL con-sortium was used as the discovery cohort,with the deCODE database serving as the validation cohort.SMR analysis and heterogeneity in dependent instruments(HEIDI)tests were conducted to assess the association and heterogeneity between oxidative stress-related genes and PCa.Colocalization analysis was performed to determine whether oxidative stress-related genes and PCa shared common causal variants.Final-ly,CCK-8 assays,wound healing assays,and Transwell invasion assays and Western blotting,were con-ducted to examine the effects of oxidative stress-related genes on the biological behavior of the PCa cell line C4-2.Results:Multi-omics analysis identified SCP2 as significantly associated with increased PCa risk across gene methylation,gene expression,and circulating protein levels.GSTP1 showed significant associations at the methylation and protein levels,while LPO was associated at the protein level.At the methylation level,SCP2 sites cg00581603(OR=1.11,95％CI:1.05-1.17)and cg13078931(OR=1.12,95％CI:1.05-1.18)were identified as pathogenic.Among the four methylation sites in GSTP1,only cg05244766(OR=0.89,95％CI:0.84-0.95)was considered protective.At the gene expression level,SCP2(OR=1.05,95％CI:1.02-1.07)was also found to be a pathogenic factor.At the circu-lating protein level,SCP2(OR=2.10,95％CI:1.34-3.29)showed a consistent pathogenic trend.In addition,GSTP1(OR=1.16,95％CI:1.07-1.25)and LPO(OR=1.12,95％CI:1.05-1.19)were significantly associated with increased PCa risk.Further functional assays demonstrated that knock-down of SCP2 significantly reduced the oncogenic phenotype of prostate cancer cells.Conclusion:Through integrated multi-omics analysis and experimental validation,this study confirmed a significant as-sociation between SCP2 and increased PCa risk.These findings enhance our understanding of PCa patho-genesis and provide new potential targets and therapeutic directions for PCa treatment.

BACKGROUND:According to different locations of lumbar disc herniation,it can be classified into many types.Among them,patients with intradural sac type lumbar disc herniation have severe clinical symptoms,which greatly affect their quality of life.Therefore,this article studies the risk factors for its onset,and improving the preoperative diagnostic rate is of great significance for the treatment and prevention of this disease.OBJECTIVE:To explore the risk factors for intradural lumbar disc herniation.METHODS:A retrospective analysis was conducted on 15 patients with intradural lumbar disc herniation(herniation group)admitted to three hospitals in Xuzhou city from May 2014 to November 2022.Propensity score matching was used to match patients with lumbar disc herniation who did not protrude into the dura mater in a ratio of 1:4.A total of 59 patients were selected and included in the non-herniation group.Clinical data were observed in the two groups.Univariate and binary logistic regression analysis,multiple linear regression,and PROBIT regression analysis were utilized to identify the relevant risk factors for intradural lumbar disc herniation.RESULTS AND CONCLUSION:(1)The results of univariate analysis showed that the average disease course,proportion of segments,modified Pfiirmann grading,sacral tilt angle,proportion of previous lumbar spine surgery history,and proportion of heavy manual workers,proportion of lumbar spinal stenosis,redundancy of the cauda equina,and ossification of the posterior longitudinal ligament all showed statistical differences in the herniation and non-herniation groups(P＜0.05).(2)Multivariate regression analysis showed that duration of disease,protruding segment,history of lumbar surgery,modified Pfiirmann grading,cauda equina redundancy,and lumbar spinal stenosis were independent risk factors for intradural lumbar disc herniation.(3)Based on the influencing factors,an receiver operating characteristic curve was constructed,with an area under curve of 0.956(95％CI:0.913-0.998),indicating good discrimination.(4)There was a significant correlation between the duration of the disease,the protruded segment,the history of lumbar spine surgery,the modified Pfirmann classification,cauda equina redundancy,lumbar spinal canal stenosis,and the incidence rate of intradural lumbar disc herniation.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.