BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

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.

Objective To investigate the heterogeneity and key molecular features of epithelial cells in triple-negative breast cancer (TNBC), identify prognostic biomarkers, and develop a robust survival prediction model. Methods Using TNBC single-cell transcriptomic data, epithelial cells were extracted, normalized, and subclustered to characterize their molecular signatures and functional differences. High-dimensional weighted gene co-expression network analysis (hdWGCNA) was applied to establish co-expression modules in epithelial cells. Multiple machine learning algorithms were integrated to select key prognostic genes and develop a risk-score model, whose performance was evaluated using receiver operating characteristic (ROC) curves and Kaplan-Meier (K-M) survival analysis. In addition, the immune microenvironment features and potential drug-response differences between the high- and low-risk groups were systematically assessed. Finally, PCR was performed to validate the expression differences of the key genes between tumor and normal tissues. Results We characterized the composition and molecular features of TNBC epithelial subpopulations and identified a TNBC-associated epithelial subset. By integrating hdWGCNA with machine learning approaches, 10 key genes were selected to construct a prognostic model, which effectively stratified patients into distinct survival-risk groups and demonstrated favorable predictive performance in ROC and K-M analyses. Immune profiling revealed the differences in the infiltration levels of seven immune cell types and immune function-related features between the high- and low-risk groups. Drug-sensitivity analysis suggested potential differential responses to eight agents across the risk groups. PCR validation further confirmed the differential expression of the ten signature genes between tumor and normal tissues. Conclusion This study reveals epithelial heterogeneity in TNBC at single-cell resolution and establishes a 10-gene prognostic model, which may facilitate the stratification of TNBC risk and the evaluation of immune characteristics and potential therapeutic strategies.

Clinical death refers to the permanent cessation of life functions. This article reviews the definition of clinical death and the various scenarios in which it occurs, classifies the process of clinical death, and discusses the criteria for determining uncontrollable cardiac death, controllable cardiac death and the criteria and workflow for determining brain death. It elaborates on the relationship between brain death and death, and proposes the areas to note when standardizing the medical documentation of death cases. Based on this, it introduces the content of the management system and workflow construction for death determination in medical institutions, including management structure, personnel qualifications, document norms, quality control system and training mechanism. Paying attention to the construction of the management system and workflow for death determination in medical institutions is of great significance for ensuring medical quality and safety, promoting the healthy development of organ donation, and maintaining the seriousness of legal and ethical practices.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

BACKGROUND:Gait dysfunction is one of the significant reasons for patient dissatisfaction following total knee arthroplasty.Clinical studies have identified a relationship between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction,but the exact nature of this correlation is not yet fully understood.OBJECTIVE:To investigate the correlation between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction in total knee arthroplasty.METHODS:A retrospective analysis was conducted on longitudinal data from 70 patients who underwent unilateral primary total knee arthroplasty.Preoperative measurements included peak torque of the extensor and flexor muscles,peak torque/body weight,and total work.Six months postoperatively,the Timed Up and Go Test and gait speed were measured.Ridge regression analysis was used to identify factors influencing postoperative gait function.RESULTS AND CONCLUSION:(1)Preoperative peak torque,peak torque/body weight,and total work of the extensor muscles,as well as the peak torque and total work of the flexor muscles,showed a very strong positive correlation with postoperative gait speed(P＜0.001).The preoperative flexor muscle peak torque/body weight had a strong positive correlation with postoperative gait speed(P＜0.001).Preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work showed a very strong negative correlation with results from postoperative Timed Up and Go Test(P＜0.001).(2)Ridge regression analysis indicated a 94.2％likelihood that preoperative extensor muscle peak torque,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a positive impact on gait speed after total knee arthroplasty(P＜0.001).The preoperative flexor muscle peak torque/body weight had a negative impact on postoperative gait speed(P＜0.001).There was an 87.7％likelihood that preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a negative impact on postoperative Timed Up and Go Test(P＜0.05),while the flexor muscle peak torque/body weight had no impact on the Timed Up and Go Test(P＞0.05).(3)It is indicated that the strength of the quadriceps and hamstring muscles prior to total knee arthroplasty correlates with postoperative gait speed and Timed Up and Go Test,and can predict the outcomes of postoperative gait function.Enhancing preoperative knee muscle exercises may be a way to reduce the incidence of gait dysfunction following total knee arthroplasty.

Objective To study the expression of regulator of cullins-1(ROC1)and ubiquitin binding enzyme 9(UBC9)in non-muscle invasive bladder cancer(NMIBC)and their relationship with clinicopathological features and prognostic value of transurethral resection of bladder tumor(TURBT).Methods Retrospective analysis was conducted on 104 patients with NMIBC who underwent TURBT at Northwest University First Hospital from April 2018 to February 2021.Immunohistochemistry was used to detect the expression of ROC1 and UBC9 in tissues.Follow-up was conducted for 3 years,and Kaplan-Meier curve analysis and COX regression analysis were used to identify factors affecting the prognosis of NMIBC patients.Results The positive rates of ROC1(67.31%)and UBC9(69.23%)in NMIBC cancer tissues were higher than those in adjacent tissues(9.62%,7.69%),and the differences were statistically significant(χ2=73.125,83.200,all P<0.001).There was a positive correlation between the expression of ROC1 and UBC9 in NMIBC cancer(r=0.719,P<0.001).The positivity rates of ROC1(87.23%,90.00%)and UBC9(89.36%,88.33%)in cancer tissues with a maximum tumor diameter of≥2cm,T1 stage were higher than those in cancer tissues with a maximum tumor diameter of<2cm(50.88%,52.63%),Ta/Tis stage(36.36%,43.18%),and the difference were statistically significant(χ2=15.474～33.188,all P<0.05).After TURBT surgery,there were 29 cases of local recurrence,10 cases of metastasis,and 2 deaths of bladder cancer,the 3-year progression-free survival(PFS)rate was 60.58%(63/104).The 3-year PFS of NMIBC patients in the ROC1 positive and negative groups was 47.14%(33/70)and 88.24%(30/34),and the 3-year PFS of patients in the UBC9 positive and negative groups was 47.22%(34/72)and 90.63%(29/32),the differences were statistically significant(Log-rank χ2=15.341,15.931,all P<0.001).Multivariate COX regression analysis showed that ROC1 positivity,UBC9 positivity,maximum tumor diameter≥2cm and T1 phase were risk factors affecting the prognosis of NMIBC patients(all P<0.001).Conclusion The expression of ROC1 and UBC9 is elevated in NMIBC,which is related to the maximum diameter and stage of the tumor.Combined detection of ROC1 and UBC9 can help evaluate the prognosis of NMIBC patients.

BACKGROUND:Gait dysfunction is one of the significant reasons for patient dissatisfaction following total knee arthroplasty.Clinical studies have identified a relationship between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction,but the exact nature of this correlation is not yet fully understood.OBJECTIVE:To investigate the correlation between the preoperative strength of the quadriceps and hamstring muscles and postoperative gait dysfunction in total knee arthroplasty.METHODS:A retrospective analysis was conducted on longitudinal data from 70 patients who underwent unilateral primary total knee arthroplasty.Preoperative measurements included peak torque of the extensor and flexor muscles,peak torque/body weight,and total work.Six months postoperatively,the Timed Up and Go Test and gait speed were measured.Ridge regression analysis was used to identify factors influencing postoperative gait function.RESULTS AND CONCLUSION:(1)Preoperative peak torque,peak torque/body weight,and total work of the extensor muscles,as well as the peak torque and total work of the flexor muscles,showed a very strong positive correlation with postoperative gait speed(P＜0.001).The preoperative flexor muscle peak torque/body weight had a strong positive correlation with postoperative gait speed(P＜0.001).Preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work showed a very strong negative correlation with results from postoperative Timed Up and Go Test(P＜0.001).(2)Ridge regression analysis indicated a 94.2％likelihood that preoperative extensor muscle peak torque,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a positive impact on gait speed after total knee arthroplasty(P＜0.001).The preoperative flexor muscle peak torque/body weight had a negative impact on postoperative gait speed(P＜0.001).There was an 87.7％likelihood that preoperative extensor and flexor muscle peak torques,peak torque/body weight,and total work,along with flexor muscle peak torque and total work,had a negative impact on postoperative Timed Up and Go Test(P＜0.05),while the flexor muscle peak torque/body weight had no impact on the Timed Up and Go Test(P＞0.05).(3)It is indicated that the strength of the quadriceps and hamstring muscles prior to total knee arthroplasty correlates with postoperative gait speed and Timed Up and Go Test,and can predict the outcomes of postoperative gait function.Enhancing preoperative knee muscle exercises may be a way to reduce the incidence of gait dysfunction following total knee arthroplasty.

Objective:To summarize and investigate the ultrasound manifestations, clinical characteristics, causes, and prognosis of hepatic portal vein gas (HPVG) after liver transplantation in children.Methods:A case series study. Clinical data of 9 pediatric recipients diagnosed with HPVG by ultrasound after liver transplantation between January 2012 and August 2023 were collected, and the ultrasound manifestations, causes, clinical features, and prognosis of HPVG were analyzed.Results:A total of 1,850 pediatric liver transplantations were performed during the same period in Tianjin First Central Hospital, among which 9 cases (0.48%) developed HPVG; 6 cases occurred within 1 month after surgery, and 3 cases occurred more than 1 month after surgery; the duration ranged from 2 to 15 days, with a median of 7 (4.5, 9.0) days. HPVG was first detected by ultrasound in all cases, with common ultrasound manifestations including bubble-like or punctate strong echoes flowing with blood in the portal vein, and patchy strong echoes with unclear borders in the liver parenchyma. Among the 9 patients, 3 had diarrhea with intestinal flora imbalance, 2 had abdominal distension with incomplete intestinal obstruction, 1 had colonic fistula with repeated replacement of Li's tube and concurrent abdominal distension, 1 was experiencing acute T-cell-mediated rejection of the transplanted liver, and the remaining 2 were asymptomatic. Patients with diarrhea and intestinal dysbiosis were treated with Bifidobacterium Lactobacillus triple viable tablets to regulate flora and montmorillonite powder to relieve diarrhea, which gradually subsided. Patients with abdominal distension and incomplete intestinal obstruction were treated with fasting, intravenous nutrition, and enema, and the obstruction gradually resolved, along with disappearance of HPVG.Conclusion:HPVG after liver transplantation has characteristic ultrasound manifestations, and its occurrence may be related to intestinal gas, obstruction, dysbiosis, or mucosal damage. Treatment may be conservative or surgical depending on the underlying cause and severity.

Objective To study the expression of regulator of cullins-1(ROC1)and ubiquitin binding enzyme 9(UBC9)in non-muscle invasive bladder cancer(NMIBC)and their relationship with clinicopathological features and prognostic value of transurethral resection of bladder tumor(TURBT).Methods Retrospective analysis was conducted on 104 patients with NMIBC who underwent TURBT at Northwest University First Hospital from April 2018 to February 2021.Immunohistochemistry was used to detect the expression of ROC1 and UBC9 in tissues.Follow-up was conducted for 3 years,and Kaplan-Meier curve analysis and COX regression analysis were used to identify factors affecting the prognosis of NMIBC patients.Results The positive rates of ROC1(67.31%)and UBC9(69.23%)in NMIBC cancer tissues were higher than those in adjacent tissues(9.62%,7.69%),and the differences were statistically significant(χ2=73.125,83.200,all P<0.001).There was a positive correlation between the expression of ROC1 and UBC9 in NMIBC cancer(r=0.719,P<0.001).The positivity rates of ROC1(87.23%,90.00%)and UBC9(89.36%,88.33%)in cancer tissues with a maximum tumor diameter of≥2cm,T1 stage were higher than those in cancer tissues with a maximum tumor diameter of<2cm(50.88%,52.63%),Ta/Tis stage(36.36%,43.18%),and the difference were statistically significant(χ2=15.474～33.188,all P<0.05).After TURBT surgery,there were 29 cases of local recurrence,10 cases of metastasis,and 2 deaths of bladder cancer,the 3-year progression-free survival(PFS)rate was 60.58%(63/104).The 3-year PFS of NMIBC patients in the ROC1 positive and negative groups was 47.14%(33/70)and 88.24%(30/34),and the 3-year PFS of patients in the UBC9 positive and negative groups was 47.22%(34/72)and 90.63%(29/32),the differences were statistically significant(Log-rank χ2=15.341,15.931,all P<0.001).Multivariate COX regression analysis showed that ROC1 positivity,UBC9 positivity,maximum tumor diameter≥2cm and T1 phase were risk factors affecting the prognosis of NMIBC patients(all P<0.001).Conclusion The expression of ROC1 and UBC9 is elevated in NMIBC,which is related to the maximum diameter and stage of the tumor.Combined detection of ROC1 and UBC9 can help evaluate the prognosis of NMIBC patients.