Objective To investigate the expression and mechanistic role of the M2-type pyruvate kinase(PKM2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in the development of experimental autoim-mune uveitis(EAU).Methods Eighteen 4-to 5-week-old C57BL/6J mice were selected and randomly divided into a control group(normal breeding,set as the 0-day state post-modeling),Experimental Group A,and Experimental Group B(both established as stable EAU mouse models using the interphotoreceptor retinoid-binding protein peptide 651-670,com-plete Freund's adjuvant,and pertussis toxin,designated as the 14-day and 21-day states post-modeling,respectively),with 6 mice in each group.The anterior segment of the mice was observed using a slit-lamp microscope,fundus findings were collected using a fundus camera,and clinical and histopathological scores were evaluated after hematoxylin-eosin stai-ning.The protein expression level of serum interleukin(IL)-17A was detected by ELISA.The expression level of PKM2 protein in retinal tissue was detected by immunohistochemistry.The protein expression levels of PKM2,phosphorylated STAT3(p-STAT3),and STAT3 in mouse retinal tissue were detected by Western blot.Results The clinical scores of the anterior segment and fundus,as well as the retinal histopathological scores in Experimental Group A and Experimental Group B,were all significantly higher than those in the control group(all P＜0.05).The serum IL-17A protein expression levels in the control group,Experimental Group A,and Experimental Group B were(69.05±0.45)ng·L-1,(75.06±0.46)ng·L-1,and(72.04±0.82)ng·L-1,respectively.The optical density values of PKM2 protein expression in retinal tissue were(18.51±2.59)％,(37.35±4.67)％,and(29.75±2.17)％,respectively.The expression levels of serum IL-17A protein,retinal PKM2 protein,and retinal STAT3 and p-STAT3 proteins in Experimental Group A and Experimental Group B were all significantly higher than those in the control group(all P＜0.05).Conclusion The expression levels of key factors in the PKM2/STAT3 signaling pathway are positively correlated with the severity of EAU,indicating that this sig-naling pathway,as a positive regulator of the immune response,is involved in the pathological process of EAU.

Objective To investigate the expression and role of T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)in the pathogenesis of experimental autoimmune uveitis(EAU).Methods A total of 12 male C57BL/6J mice,aged 4 to 5 weeks,were selected and divided into the control group(n=3)and the experimental group(n=9)using a random number table.The control group(modeling time point:0 days after modeling)received no treatment,while the experimental group was induced to establish an EAU model(divided into three subgroups according to the modeling time points:7 days,14 days,and 21 days after modeling,with 3 mice in each subgroup).Firstly,the interphotoreceptor retinoid-binding protein 651-670 and complete Freund's adjuvant were fully mixed and emulsified.Then,the emulsion was subcutaneously injected into the two thighs,tail base,and neck of mice in the experimental group(each mouse received 200 μL of immune emulsion containing 500 pg of interphotoreceptor retinoid-binding protein 651-670).Subsequently,each mouse in the experimental group was also intraperitoneally injected with 1 μg of pertussis toxin.The anterior segment and fundus of mice in each group were observed and photographed under a slit-lamp microscope.The clinical and histopatho-logical scoring of these mice was conducted according to the Caspi grading scale based on the severity of inflammation.The serum levels of IFN-γ and IL-17 were measured using the enzyme-linked immunosorbent assay(ELISA),while the mRNA expression of Tim-3 in the spleen and ocular tissues was detected using the real-time quantitative polymerase chain reaction(RT-qPCR).Western blot was employed to detect the protein expression of Tim-3,and immunohistochemistry was used to examine the protein expression of Tim-3 in the spleen tissue.Statistical analysis was performed using GraphPad Prism 9.0.Results The clinical scores of the anterior segment,fundus,and histopathology of the mice increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The serum levels of IFN-γ and IL-17 in the mice also increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The relative mRNA expression of Tim-3 in the spleen and ocular tissues of the mice decreased over time after modeling,with statistically significant differences among these groups(P＜0.05).The protein expression of Tim-3 in the ocular and spleen tissues showed the same pattern as its mRNA expression.Conclusion The expression of Tim-3 decreases with the exacerbation of inflammation in the progression of EAU,suggesting that Tim-3 may play a negative immunoregulatory role in the development of uveitis.

Objective To investigate the expression and mechanistic role of the M2-type pyruvate kinase(PKM2)/signal transducer and activator of transcription 3(STAT3)signaling pathway in the development of experimental autoim-mune uveitis(EAU).Methods Eighteen 4-to 5-week-old C57BL/6J mice were selected and randomly divided into a control group(normal breeding,set as the 0-day state post-modeling),Experimental Group A,and Experimental Group B(both established as stable EAU mouse models using the interphotoreceptor retinoid-binding protein peptide 651-670,com-plete Freund's adjuvant,and pertussis toxin,designated as the 14-day and 21-day states post-modeling,respectively),with 6 mice in each group.The anterior segment of the mice was observed using a slit-lamp microscope,fundus findings were collected using a fundus camera,and clinical and histopathological scores were evaluated after hematoxylin-eosin stai-ning.The protein expression level of serum interleukin(IL)-17A was detected by ELISA.The expression level of PKM2 protein in retinal tissue was detected by immunohistochemistry.The protein expression levels of PKM2,phosphorylated STAT3(p-STAT3),and STAT3 in mouse retinal tissue were detected by Western blot.Results The clinical scores of the anterior segment and fundus,as well as the retinal histopathological scores in Experimental Group A and Experimental Group B,were all significantly higher than those in the control group(all P＜0.05).The serum IL-17A protein expression levels in the control group,Experimental Group A,and Experimental Group B were(69.05±0.45)ng·L-1,(75.06±0.46)ng·L-1,and(72.04±0.82)ng·L-1,respectively.The optical density values of PKM2 protein expression in retinal tissue were(18.51±2.59)％,(37.35±4.67)％,and(29.75±2.17)％,respectively.The expression levels of serum IL-17A protein,retinal PKM2 protein,and retinal STAT3 and p-STAT3 proteins in Experimental Group A and Experimental Group B were all significantly higher than those in the control group(all P＜0.05).Conclusion The expression levels of key factors in the PKM2/STAT3 signaling pathway are positively correlated with the severity of EAU,indicating that this sig-naling pathway,as a positive regulator of the immune response,is involved in the pathological process of EAU.

Objective:To examine the dynamic interactive relationships between cyberbullying perpetration,anxiety,and depression in college students.Methods:A total of 4 148 college students from a comprehensive uni-versity in Guangxi Zhuang Autonomous Region completed self-report measures including Cyberbullying Scale(CS),Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)at two time points,18-month a-part.Results:Correlation analysis showed significant concurrent(r=0.11-0.17,Ps＜0.001)and lagged(r=0.06-0.44,Ps＜0.001)positive associations among CS,SAS,and SDS scores.Cross-lagged analysis,controlling for gender and age,indicated that T1 CS scores were positively associated with T2 SAS and SDS scores(β=0.13,0.14,Ps＜0.001).Additionally,SAS scores at T1 and SDS scores at T1 were positively associated CS scores at T2,respectively(β=0.07,0.05,Ps＜0.001).Conclusion:Cyberbullying perpetration,anxiety,and depression in-fluence each other over time among college students,suggesting a reinforcing negative cycle.

Background: Apolipoprotein A-I (ApoA-I) is a key cardioprotective lipoprotein. Nevertheless, it remains unclear how ApoA-I relates to ischemic risk across glucose metabolism statuses in patients with coronary artery disease (CAD). This study investigated whether glucose metabolism status influences the association between ApoA-I and ischemic risk in CAD patients. Methods: This cohort study included 10,724 consecutive CAD patients undergoing percutaneous coronary intervention, who were classified into diabetes mellitus (DM), pre-DM, and normal glucose regulation (NGR) groups. The primary clinical endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction, revascularization, and stroke. Results: Of the 10,232 patients ultimately included, 2,139 (20.9%) experienced MACCE over 5 years. A significant interaction was observed between ApoA-I levels and glucose metabolism status (P for interaction=0.041). In the DM group, an L-shaped association between ApoA-I and MACCE was found, with lower ApoA-I levels linked to a higher risk of MACCE (P for non-linearity= 0.044). Multivariate Cox regression analysis showed that patients in the lowest quintile of ApoA-I had a 1.327-fold increased risk of MACCE compared to those at the lowest risk (hazard ratio, 1.327; 95% confidence interval, 1.097 to 1.604). However, no significant association was observed in the pre-DM or NGR groups (both P>0.05). Conclusion This large-scale, 5-year follow-up study is the first to demonstrate that lower ApoA-I levels are associated with increased MACCE risk in CAD patients with DM, highlighting the potential value of ApoA-I in risk stratification and as a therapeutic target.

Objective To investigate the expression and role of T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)in the pathogenesis of experimental autoimmune uveitis(EAU).Methods A total of 12 male C57BL/6J mice,aged 4 to 5 weeks,were selected and divided into the control group(n=3)and the experimental group(n=9)using a random number table.The control group(modeling time point:0 days after modeling)received no treatment,while the experimental group was induced to establish an EAU model(divided into three subgroups according to the modeling time points:7 days,14 days,and 21 days after modeling,with 3 mice in each subgroup).Firstly,the interphotoreceptor retinoid-binding protein 651-670 and complete Freund's adjuvant were fully mixed and emulsified.Then,the emulsion was subcutaneously injected into the two thighs,tail base,and neck of mice in the experimental group(each mouse received 200 μL of immune emulsion containing 500 pg of interphotoreceptor retinoid-binding protein 651-670).Subsequently,each mouse in the experimental group was also intraperitoneally injected with 1 μg of pertussis toxin.The anterior segment and fundus of mice in each group were observed and photographed under a slit-lamp microscope.The clinical and histopatho-logical scoring of these mice was conducted according to the Caspi grading scale based on the severity of inflammation.The serum levels of IFN-γ and IL-17 were measured using the enzyme-linked immunosorbent assay(ELISA),while the mRNA expression of Tim-3 in the spleen and ocular tissues was detected using the real-time quantitative polymerase chain reaction(RT-qPCR).Western blot was employed to detect the protein expression of Tim-3,and immunohistochemistry was used to examine the protein expression of Tim-3 in the spleen tissue.Statistical analysis was performed using GraphPad Prism 9.0.Results The clinical scores of the anterior segment,fundus,and histopathology of the mice increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The serum levels of IFN-γ and IL-17 in the mice also increased over time after modeling,with statistically significant differences among these groups(P＜0.05).The relative mRNA expression of Tim-3 in the spleen and ocular tissues of the mice decreased over time after modeling,with statistically significant differences among these groups(P＜0.05).The protein expression of Tim-3 in the ocular and spleen tissues showed the same pattern as its mRNA expression.Conclusion The expression of Tim-3 decreases with the exacerbation of inflammation in the progression of EAU,suggesting that Tim-3 may play a negative immunoregulatory role in the development of uveitis.

Objective:To examine the dynamic interactive relationships between cyberbullying perpetration,anxiety,and depression in college students.Methods:A total of 4 148 college students from a comprehensive uni-versity in Guangxi Zhuang Autonomous Region completed self-report measures including Cyberbullying Scale(CS),Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)at two time points,18-month a-part.Results:Correlation analysis showed significant concurrent(r=0.11-0.17,Ps＜0.001)and lagged(r=0.06-0.44,Ps＜0.001)positive associations among CS,SAS,and SDS scores.Cross-lagged analysis,controlling for gender and age,indicated that T1 CS scores were positively associated with T2 SAS and SDS scores(β=0.13,0.14,Ps＜0.001).Additionally,SAS scores at T1 and SDS scores at T1 were positively associated CS scores at T2,respectively(β=0.07,0.05,Ps＜0.001).Conclusion:Cyberbullying perpetration,anxiety,and depression in-fluence each other over time among college students,suggesting a reinforcing negative cycle.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Objective:To evaluate the clinical outcomes of applying an enhanced workflow in robotic-assisted total hip revision arthroplasty.Methods:A retrospective study was conducted to analyze the 25 consecutive patients who had undergone robotic-assisted total hip revision arthroplasty in which an enhanced workflow was applied at Department of Orthopaedic Surgery, Beijing Jishuitan Hospital from September 2021 to October 2024. The cohort consisted of 8 males and 17 females with an age of (64.0±12.8) years. The left side was affected in 18 cases and the right side in 7 cases. The time from initial total hip arthroplasty to revision was (159.6±86.7) months. In all patients, no significant difference was found in the preoperative femoral cortical thickness between the healthy and the affected sides. The enhanced workflow included preoperative CT modeling and planning, intraoperative registration, prosthetic removal and reconstruction, and verification of prosthesis position. A total of 18 patients underwent total hip revision involving both the acetabular and the femoral sides; 6 patients underwent simple acetabular reconstruction with retention of the original femoral stem and replacement of the femoral head; 1 patient underwent femoral revision with retention of the acetabular cup and replacement of the acetabular liner. The operative time, intraoperative blood loss, modified Harris Hip Score (mHHS) and visual analogue scale (VAS) for hip pain at the final follow-up, and follow-up complications were recorded.Results:All patients successfully completed robotic registration during surgery, with no case of intraoperative robotic termination. For the 25 patients, the operative time was (152.2±43.8) minutes, the intraoperative blood loss 600 (400, 1,000) mL, and the follow-up time 12.0 (6.0, 31.5) months. At the final follow-up, their mHHS improved from 66.0 (26.4, 75.6) points preoperatively to 93.5 (80.3, 98.9) points, and their VAS pain score decreased from 5.0 (3.0, 7.0) points preoperatively to 0.0 (0.0, 2.0) point ( P<0.05). Follow-ups revealed no case of reoperation, prosthetic loosening, joint dislocation, periprosthetic infection, or periprosthetic fracture. Conclusion:The enhanced workflow can achieve satisfactory outcomes in robotic-assisted total hip revision for patients with adequate proximal femoral bone stock.

Objective:To evaluate the clinical outcomes of applying an enhanced workflow in robotic-assisted total hip revision arthroplasty.Methods:A retrospective study was conducted to analyze the 25 consecutive patients who had undergone robotic-assisted total hip revision arthroplasty in which an enhanced workflow was applied at Department of Orthopaedic Surgery, Beijing Jishuitan Hospital from September 2021 to October 2024. The cohort consisted of 8 males and 17 females with an age of (64.0±12.8) years. The left side was affected in 18 cases and the right side in 7 cases. The time from initial total hip arthroplasty to revision was (159.6±86.7) months. In all patients, no significant difference was found in the preoperative femoral cortical thickness between the healthy and the affected sides. The enhanced workflow included preoperative CT modeling and planning, intraoperative registration, prosthetic removal and reconstruction, and verification of prosthesis position. A total of 18 patients underwent total hip revision involving both the acetabular and the femoral sides; 6 patients underwent simple acetabular reconstruction with retention of the original femoral stem and replacement of the femoral head; 1 patient underwent femoral revision with retention of the acetabular cup and replacement of the acetabular liner. The operative time, intraoperative blood loss, modified Harris Hip Score (mHHS) and visual analogue scale (VAS) for hip pain at the final follow-up, and follow-up complications were recorded.Results:All patients successfully completed robotic registration during surgery, with no case of intraoperative robotic termination. For the 25 patients, the operative time was (152.2±43.8) minutes, the intraoperative blood loss 600 (400, 1,000) mL, and the follow-up time 12.0 (6.0, 31.5) months. At the final follow-up, their mHHS improved from 66.0 (26.4, 75.6) points preoperatively to 93.5 (80.3, 98.9) points, and their VAS pain score decreased from 5.0 (3.0, 7.0) points preoperatively to 0.0 (0.0, 2.0) point ( P<0.05). Follow-ups revealed no case of reoperation, prosthetic loosening, joint dislocation, periprosthetic infection, or periprosthetic fracture. Conclusion:The enhanced workflow can achieve satisfactory outcomes in robotic-assisted total hip revision for patients with adequate proximal femoral bone stock.