Objective To investigate the causal relationship between metabolic syndrome and breast cancer by using a bidirectional two-sample Mendelian randomization (MR) approach. Methods Genome-wide association study (GWAS) summary statistics for metabolic syndrome and breast cancer were acquired from the Integrative Epidemiology Unit GWAS database and the GWAS Catalog, with populations encompassing the United States and East Asia. A bidirectional causal design was employed: a forward analysis with metabolic syndrome as the exposure and breast cancer as the outcome, followed by a reverse analysis wherein their roles were interchanged. The inverse-variance weighting (IVW) method was primarily used for effect estimation, supplemented by MR-Egger regression, the weighted median method, the simple mode method, and the weighted mode method. Instrument variable strength was screened using the F-statistic (F>10). Robustness of the results was assessed through heterogeneity tests, horizontal pleiotropy tests, forest plots, and leave-one-out sensitivity analyses. Results The IVW analysis indicated no significant causal relationship between metabolic syndrome and breast cancer (OR=1.00, 95%CI: 0.97-1.03), P>0.05). Sensitivity analyses yielded consistent results, suggesting the good robustness of the study findings. Conclusion This study found no evidence to support a causal relationship, either positive or negative, between metabolic syndrome and breast cancer.

Objective:To analyze the changes in the prevalence characteristics of multimorbidity among adolescents aged 13-18 in Inner Mongolia Autonomous Region from 2019 to 2022 and to explore the association between multimorbidity and moderate to high-intensity physical activity among them.Methods:A stratified random cluster sampling method was used to select students aged 13-18 in Inner Mongolia Autonomous Region every September from 2019 to 2022. Physical examinations, demographic characteristics, and depression-related surveys were conducted to analyze the multimorbidity of overweight, obesity, high blood pressure, myopia, spinal curvature abnormality, and depression. A logistic regression model was used to analyze the association between multimorbidity and moderate to high-intensity physical activity.Results:From 2019 to 2022, 70 972, 62 923, 80 254, and 78 288 study subjects were included, with the rates of multimorbidity being 56.4%, 55.4%, 57.2%, and 55.8%, respectively. The rates of multimorbidity remained relatively stable from 2019 to 2022 ( χ2=0.06, P=0.950). The incidence of multimorbidity among girls was significantly higher than that among boys ( P<0.001). The incidence of multimorbidity among urban students was significantly higher than that among suburban students ( P<0.001). The incidence of multimorbidity among high school students was higher than that among middle school students ( P<0.001). The top three multimorbidity combinations were myopia and overweight/obesity (26.4%), myopia and high blood pressure (24.4%), and myopia and depression (19.8%), while the least common combination was depression and spinal curvature abnormality (1.1%). The multimorbidity patterns showed no significant differences between years ( χ2=0.03, P=0.999). The multimorbidity status was significantly associated with the status of meeting the standard of moderate to high-intensity physical activity ( OR=0.83, 95% CI: 0.80-0.86). The association was stronger in boys ( OR=0.77, 95% CI: 0.73-0.81) compared with girls ( OR=0.90, 95% CI: 0.85-0.96), with a significant interaction term ( P<0.001). Conclusion:From 2019 to 2022, the incidence of multimorbidity among adolescents aged 13 to 18 in Inner Mongolia Autonomous Region is relatively high, mainly due to the co-occurrence of myopia and other health problems. Adequate physical activity is an important factor in reducing multimorbidity.

Objective:To evaluate the safety, efficacy, advantages and disadvantages of the modified double-orifice valve plasty via total thoracoscopy for partial atrioventricular septal defect(PAVSD) through a retrospective analysis of early postoperative results.Methods:Patients diagnosed with PAVSD who underwent the standardized modified double-orifice valve plasty via total thoracoscopy between September 2023 and August 2024 were retrospectively enrolled. Baseline characteristics, surgical parameters, and follow-up outcomes were systematically analyzed.Results:A total of 14 patients(6 males, 8 females) were included, with a mean age of(32.9±15.5) years old and body weight of(55.1±11.6) kg. All procedures were successfully completed. The mean operative time, cardiopulmonary bypass time, and aortic cross-clamp time were(266.6±67.2) min, (160.7±34.2) min, and(97.0±31.1) min, respectively. Postoperative ICU stay, hospital stay, and total hospitalization duration were(1.7±1.1) days, (6.4±4.2) days, and(12.6±4.5) days, respectively. The mean follow-up duration was(7.9±3.6) months. Preoperatively, left atrioventricular valve regurgitation(LAVVR) was graded as mild, moderate, or severe in 5, 4, and 5 patients. Postoperatively, 13 patients exhibited mild or less LAVVR, with 1 case of moderate regurgitation. By 3 months, all patients demonstrated LAVVR of mild or lower severity, which remained stable through follow-up. Peak LAVV gradients were(4.6±2.7) mmHg(1 mmHg=0.133 kPa)(range: 1.8-10.2 mmHg) postoperatively, improving to(3.6±0.6) mmHg(3.2-4.0) mmHg at 1 year. Right atrioventricular valve regurgitation improved from preoperative moderate-severe(50.0%) to LAVVR of mild or lower severity in all patients by 3 months. No mortality, residual shunts, or high-grade atrioventricular block occurred through follow-up. By 1 month, NYHA functional class improved to Ⅰ in all patients, which remained stable through follow-up.Conclusion:Standardized modified double-orifice valve plasty via total thoracoscopy for PAVSD demonstrates safety, minimal invasiveness, and rapid recovery, with favorable early outcomes.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective:To analyze the changes in the prevalence characteristics of multimorbidity among adolescents aged 13-18 in Inner Mongolia Autonomous Region from 2019 to 2022 and to explore the association between multimorbidity and moderate to high-intensity physical activity among them.Methods:A stratified random cluster sampling method was used to select students aged 13-18 in Inner Mongolia Autonomous Region every September from 2019 to 2022. Physical examinations, demographic characteristics, and depression-related surveys were conducted to analyze the multimorbidity of overweight, obesity, high blood pressure, myopia, spinal curvature abnormality, and depression. A logistic regression model was used to analyze the association between multimorbidity and moderate to high-intensity physical activity.Results:From 2019 to 2022, 70 972, 62 923, 80 254, and 78 288 study subjects were included, with the rates of multimorbidity being 56.4%, 55.4%, 57.2%, and 55.8%, respectively. The rates of multimorbidity remained relatively stable from 2019 to 2022 ( χ2=0.06, P=0.950). The incidence of multimorbidity among girls was significantly higher than that among boys ( P<0.001). The incidence of multimorbidity among urban students was significantly higher than that among suburban students ( P<0.001). The incidence of multimorbidity among high school students was higher than that among middle school students ( P<0.001). The top three multimorbidity combinations were myopia and overweight/obesity (26.4%), myopia and high blood pressure (24.4%), and myopia and depression (19.8%), while the least common combination was depression and spinal curvature abnormality (1.1%). The multimorbidity patterns showed no significant differences between years ( χ2=0.03, P=0.999). The multimorbidity status was significantly associated with the status of meeting the standard of moderate to high-intensity physical activity ( OR=0.83, 95% CI: 0.80-0.86). The association was stronger in boys ( OR=0.77, 95% CI: 0.73-0.81) compared with girls ( OR=0.90, 95% CI: 0.85-0.96), with a significant interaction term ( P<0.001). Conclusion:From 2019 to 2022, the incidence of multimorbidity among adolescents aged 13 to 18 in Inner Mongolia Autonomous Region is relatively high, mainly due to the co-occurrence of myopia and other health problems. Adequate physical activity is an important factor in reducing multimorbidity.

Objective:To evaluate the safety, efficacy, advantages and disadvantages of the modified double-orifice valve plasty via total thoracoscopy for partial atrioventricular septal defect(PAVSD) through a retrospective analysis of early postoperative results.Methods:Patients diagnosed with PAVSD who underwent the standardized modified double-orifice valve plasty via total thoracoscopy between September 2023 and August 2024 were retrospectively enrolled. Baseline characteristics, surgical parameters, and follow-up outcomes were systematically analyzed.Results:A total of 14 patients(6 males, 8 females) were included, with a mean age of(32.9±15.5) years old and body weight of(55.1±11.6) kg. All procedures were successfully completed. The mean operative time, cardiopulmonary bypass time, and aortic cross-clamp time were(266.6±67.2) min, (160.7±34.2) min, and(97.0±31.1) min, respectively. Postoperative ICU stay, hospital stay, and total hospitalization duration were(1.7±1.1) days, (6.4±4.2) days, and(12.6±4.5) days, respectively. The mean follow-up duration was(7.9±3.6) months. Preoperatively, left atrioventricular valve regurgitation(LAVVR) was graded as mild, moderate, or severe in 5, 4, and 5 patients. Postoperatively, 13 patients exhibited mild or less LAVVR, with 1 case of moderate regurgitation. By 3 months, all patients demonstrated LAVVR of mild or lower severity, which remained stable through follow-up. Peak LAVV gradients were(4.6±2.7) mmHg(1 mmHg=0.133 kPa)(range: 1.8-10.2 mmHg) postoperatively, improving to(3.6±0.6) mmHg(3.2-4.0) mmHg at 1 year. Right atrioventricular valve regurgitation improved from preoperative moderate-severe(50.0%) to LAVVR of mild or lower severity in all patients by 3 months. No mortality, residual shunts, or high-grade atrioventricular block occurred through follow-up. By 1 month, NYHA functional class improved to Ⅰ in all patients, which remained stable through follow-up.Conclusion:Standardized modified double-orifice valve plasty via total thoracoscopy for PAVSD demonstrates safety, minimal invasiveness, and rapid recovery, with favorable early outcomes.

Objective:To evaluate effects of propofol on cognitive dysfunction and underlying mechanisms after splenectomy in aged mice.Methods:Fifty SPF grade male aged mice were divided into five groups: control group, sham operation group, surgery group, sham operation + propofol group, and surgery + propofol group, with 10 mice in each group. The Morris water maze test was used to assess the learning and memory abilities of mice in each group. The hematoxylin-eosin (HE) staining and TUNEL staining were used to observe the apoptosis of brain neurons.ELISA was performed to measure the expression of inflammatory factors in brain tissues. Transmission electron microscopy was used to observe the structure of hippocampal post-synaptic density. Immunofluorescence was employed to determine the expression of ionized calcium-binding adapter molecule 1 (IBA-1) and postsynaptic density protein-95 (PSD-95) in the hippocampus. Immunohistochemistry was used to measure the expression of microtubule-associated protein tau (tau) in the cortex. The expression of B-cell lymphoma-2 (Bcl-2), recombinant Bcl-2-associated X protein (Bax), and cysteine protease-3 (Caspase-3) was determined using both immunohistochemistry and Western blot. Data were statistically analyzed using SPSS 21.0.For comparisons among multiple groups, the results of Morris water maze experiment were compared by repeated measures ANOVA, while other data comparison was conducted by one-way ANOVA, and pairwise comparisons were conducted using the LSD- t test. Results:The results of the Morris water maze test showed that the interaction effect of time and group on the escape latency of the five groups of mice was significant ( F=95.17, P<0.01). During the spatial navigation test of day 4-6, the escape latency of the surgery group was significantly higher than that of the sham operation group ( P<0.05), while the escape latency of the surgery + propofol group was significantly lower than that of the surgery group and higher than that of sham operation+ propofol group(both P<0.05). In the spatial exploration test, the number of platform crossings, the percentage of the distance traveled in the target quadrant out of the total exploration distance, and the duration spent in the target quadrant were all significantly different among the five groups of mice ( F=27.88, 50.21, 32.04, all P<0.01). These values were all lower in the surgery group compared to the sham operation group (all P<0.05), and higher in the surgery + propofol group compared to the surgery group((2.60±0.66) vs (0.80±0.40); (40.56±1.51)% vs (13.82±3.11)%; (19.25±1.31)s vs (6.12±2.00)s) (all P<0.05).ELISA results showed that the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the brain tissues of the five groups of mice were significantly different ( F=1 017.11, 583.55, 185.35, all P<0.01). The levels of TNF-α, IL-1β and IL-6 in the brain tissues of the surgery + propofol group were all lower than those in the surgery group and higher than that of sham operation+ propofol group (all P<0.05).Transmission electron microscopy results showed that the length, width, and number of synapses in the hippocampal postsynaptic density of the five groups of mice were significantly different ( F=137.06, 55.36, 19.93, all P<0.01), and these values were all higher in the surgery + propofol group compared to the surgery group (all P<0.05).Immunofluorescence results showed that the relative fluorescence intensity of PSD95 and IBA-1 in the hippocampus of the five groups of mice were significantly different ( F=14.33, 38.23, both P<0.01). The relative fluorescence intensity of PSD95 in the hippocampus of the surgery + propofol group was higher than that of the surgery group and lower than that of sham operation+ propofol group (both P<0.05), while the relative fluorescence intensity of IBA-1 in the hippocampus of the surgery + propofol group was lower than that of the surgery group and higher than that of sham operation+ propofol group (both P<0.05).TUNEL results showed that the proportion of positive apoptotic cells in the dentate gyrus (DG) region of the brain tissue of the five groups of mice was significantly different ( F=101.94, P<0.01), and this proportion was lower in the surgery + propofol group compared to the surgery group((72.15±3.71)% vs (82.24±4.40)%) and was higher than that of sham operation+ propofol group((50.64±2.36)%)(both P<0.05).Immunohistochemical and Western blot results showed that the relative expression levels of phosphorylated tau protein, Bcl-2, Bax, and Caspase-3 in the brain tissues of the five groups of mice were significantly different ( F=56.54, 50.48, 23.00, 91.10, all P<0.01). The relative expression levels of phosphorylated tau protein, Bax, and Caspase-3 in the brain tissues of the surgery + propofol group were all lower than those in the surgery group (all P<0.05), while the relative expression level of Bcl-2 was higher in the surgery + propofol group compared to the surgery group ( P<0.05). Conclusion:Propofol pretreatment can significantly alleviate postoperative learning and memory impairments in aged mice, mitigate structural damage to the hippocampal postsynaptic density, and improve postoperative cognitive dysfunction by inhibiting the neuronal apoptosis signaling pathway.

Objective:To evaluate effects of propofol on cognitive dysfunction and underlying mechanisms after splenectomy in aged mice.Methods:Fifty SPF grade male aged mice were divided into five groups: control group, sham operation group, surgery group, sham operation + propofol group, and surgery + propofol group, with 10 mice in each group. The Morris water maze test was used to assess the learning and memory abilities of mice in each group. The hematoxylin-eosin (HE) staining and TUNEL staining were used to observe the apoptosis of brain neurons.ELISA was performed to measure the expression of inflammatory factors in brain tissues. Transmission electron microscopy was used to observe the structure of hippocampal post-synaptic density. Immunofluorescence was employed to determine the expression of ionized calcium-binding adapter molecule 1 (IBA-1) and postsynaptic density protein-95 (PSD-95) in the hippocampus. Immunohistochemistry was used to measure the expression of microtubule-associated protein tau (tau) in the cortex. The expression of B-cell lymphoma-2 (Bcl-2), recombinant Bcl-2-associated X protein (Bax), and cysteine protease-3 (Caspase-3) was determined using both immunohistochemistry and Western blot. Data were statistically analyzed using SPSS 21.0.For comparisons among multiple groups, the results of Morris water maze experiment were compared by repeated measures ANOVA, while other data comparison was conducted by one-way ANOVA, and pairwise comparisons were conducted using the LSD- t test. Results:The results of the Morris water maze test showed that the interaction effect of time and group on the escape latency of the five groups of mice was significant ( F=95.17, P<0.01). During the spatial navigation test of day 4-6, the escape latency of the surgery group was significantly higher than that of the sham operation group ( P<0.05), while the escape latency of the surgery + propofol group was significantly lower than that of the surgery group and higher than that of sham operation+ propofol group(both P<0.05). In the spatial exploration test, the number of platform crossings, the percentage of the distance traveled in the target quadrant out of the total exploration distance, and the duration spent in the target quadrant were all significantly different among the five groups of mice ( F=27.88, 50.21, 32.04, all P<0.01). These values were all lower in the surgery group compared to the sham operation group (all P<0.05), and higher in the surgery + propofol group compared to the surgery group((2.60±0.66) vs (0.80±0.40); (40.56±1.51)% vs (13.82±3.11)%; (19.25±1.31)s vs (6.12±2.00)s) (all P<0.05).ELISA results showed that the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the brain tissues of the five groups of mice were significantly different ( F=1 017.11, 583.55, 185.35, all P<0.01). The levels of TNF-α, IL-1β and IL-6 in the brain tissues of the surgery + propofol group were all lower than those in the surgery group and higher than that of sham operation+ propofol group (all P<0.05).Transmission electron microscopy results showed that the length, width, and number of synapses in the hippocampal postsynaptic density of the five groups of mice were significantly different ( F=137.06, 55.36, 19.93, all P<0.01), and these values were all higher in the surgery + propofol group compared to the surgery group (all P<0.05).Immunofluorescence results showed that the relative fluorescence intensity of PSD95 and IBA-1 in the hippocampus of the five groups of mice were significantly different ( F=14.33, 38.23, both P<0.01). The relative fluorescence intensity of PSD95 in the hippocampus of the surgery + propofol group was higher than that of the surgery group and lower than that of sham operation+ propofol group (both P<0.05), while the relative fluorescence intensity of IBA-1 in the hippocampus of the surgery + propofol group was lower than that of the surgery group and higher than that of sham operation+ propofol group (both P<0.05).TUNEL results showed that the proportion of positive apoptotic cells in the dentate gyrus (DG) region of the brain tissue of the five groups of mice was significantly different ( F=101.94, P<0.01), and this proportion was lower in the surgery + propofol group compared to the surgery group((72.15±3.71)% vs (82.24±4.40)%) and was higher than that of sham operation+ propofol group((50.64±2.36)%)(both P<0.05).Immunohistochemical and Western blot results showed that the relative expression levels of phosphorylated tau protein, Bcl-2, Bax, and Caspase-3 in the brain tissues of the five groups of mice were significantly different ( F=56.54, 50.48, 23.00, 91.10, all P<0.01). The relative expression levels of phosphorylated tau protein, Bax, and Caspase-3 in the brain tissues of the surgery + propofol group were all lower than those in the surgery group (all P<0.05), while the relative expression level of Bcl-2 was higher in the surgery + propofol group compared to the surgery group ( P<0.05). Conclusion:Propofol pretreatment can significantly alleviate postoperative learning and memory impairments in aged mice, mitigate structural damage to the hippocampal postsynaptic density, and improve postoperative cognitive dysfunction by inhibiting the neuronal apoptosis signaling pathway.

AIM:To investigate the role of specific long noncoding RNA SLC25a6(lncSLC25a6)in homocys-teine(Hcy)-induced cuproptosis in cardiomyocytes.METHODS:Rat cardiomyocytes were cultured in vitro and divided into control group and Hcy group.After 48 h of intervention,the expression levels of cuproptosis-related proteins,ferre-doxin 1(FDX1)and heat shock protein 70(HSP70),were detected by Western blot and immunofluorescence staining.The oxidative stress state of cardiomyocytes was assessed using fluorescence staining,and the intracellular Cu2+levels were measured using a copper ion assay kit.Furthermore,the impact of Hcy on the expression of cuproptosis-related proteins in cardiomyocytes was analyzed following overexpression of lncSLC25a6.RESULTS:Compared with the control group,80 μmol/L Hcy significantly accelerated cardiomyocyte damage,with a notable underexpression of lncSLC25a6(P<0.05).Western blot results indicated that,compared with the control group,the expression level of FDX1 in the Hcy intervention group was significantly reduced(P<0.05),while the expression level of HSP70 was significantly elevated(P<0.05),and the expression level of copper ions in cardiomyocytes of the Hcy group was increased(P<0.05).Immunofluorescence staining showed a significant reduction in FDX1 fluorescence intensity and a significant increase in HSP70 fluorescence in-tensity in the Hcy group.Further overexpression of lncSLC25a6 significantly mitigated Hcy-induced cuproptosis in cardio-myocytes,resulting in elevated expression of FDX1 and reduced expression of HSP70(P<0.05).Pearson correlation analysis demonstrated that the expression level of lncSLC25a6 was negatively correlated with FDX1 protein expression(r=-0.676,P=0.046)and positively correlated with HSP70 expression(r=0.680,P=0.044).CONCLUSION:lnc-SLC25a6 significantly mitigates Hcy-induced cuproptosis in cardiomyocytes,positioning it as a potential therapeutic target for managing Hcy-induced cardiac injury.

Background/Aims: Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. Methods: Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. Results: The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. Conclusions For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.