BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Migraine is a common neurological disorder with a complex pathogenesis that is currently not fully understood;however,the role of mitochondrial function in migraine pathogenesis has recently attracted widespread attention.This review considers the latest research progress on the relationship between mitochondrial dysfunction and migraine,including mitochondrial energy metabolism,oxidative stress,calcium homeostasis,and neuroinflammation.We introduce the epidemiological and clinical characteristics of migraine,and provide a detailed exploration of the key role of mitochondria in these processes.Mitochondrial dysfunction may lead to increased neuronal excitability,abnormal vasoconstriction,and inflammatory responses,thereby inducing migraine.Based on the evidence of mitochondrial involvement in the pathogenesis of migraine,we propose future research directions and potential treatment strategies,with the aim of providing new ideas for the prevention and treatment of migraine.

Objective:To propose a functional method for locating the shoulder joint center of rotation aimed at rapid estimation of the upper limb reachable domain envelope, thereby informing ergonomic design and task optimization.Methods:In March 2024, shoulder kinematics during gait were recorded from ten adults using a three-dimensional motion-capture system. Assuming the existence of a point near the glenohumeral joint that maintains a fixed spatial relationship to the humerus and the acromion, we estimated both static and dynamic centers of rotation. Localization accuracy was quantified by the standard deviation of distance residuals to upper-arm markers. Upper-limb joint angles and anthropometric parameters were modeled via regression; combined with maximal joint ranges of motion, these were used to infer the reachable domain envelope.Results:The static center of rotation was located approximately twenty-two millimeters medial to the acromial landmark in the coronal plane and thirty-seven millimeters inferior to it. The standard deviation of the residuals for the distances from the dynamic shoulder joint center of rotation to upper-arm markers averaged 1.02 mm, which was 47.42% lower than that of the static center of rotation and 66.56% lower than that of the acromion. Moreover, the trajectory of this dynamic center showed a strong correlation with upper-limb joint angles ( R2>0.7) . Conclusion:The proposed method enables rapid and accurate estimation of the upper limb reachable domain envelope to support ergonomic design and may help reduce the risk of work-related musculoskeletal disorders.

Objective:This study aimed to clarify clinicopathologic characteristics, postoperative complications, and related risk factors of elderly patients with gastric cancer.Methods:A total of 395 patients(≥65 years old)who underwent radical gastrectomy for gastric cancer in Beijing Hospital from January 2014 to December 2021 were enrolled in this study.The patients were divided into the common elderly group(age<80 years, n=340)and the high-age group(age ≥ 80 years, n=55). Postoperative complications were classified into medical and surgical types.The clinicopathological characteristics and complications were compared between the two groups.Logistic regression models(univariate and multivariate)were used to identify the risk factors for postoperative complications.Results:The common elderly group was 65-79 years old(mean age: 71.5±4.3 years), with 263 male(77.4%); The high-age group was 80-89 years old(mean age: 82.6±2.6 years), with 42 male(76.4%). The comorbidity rate and the number of comorbidities in the high-age group were significantly higher than those in the common elderly group.The American Society of Anesthesiologists(ASA)scores and nutritional risk screening(NRS)2002 scores in the high-age group were significantly higher than those in the common elderly group(both P<0.05), and the activities of daily living(ADL)scores in the high-age group were significantly lower than that in the common elderly group( P<0.001). There were no statistically significant differences in tumor location, degree of differentiation, pathological type, T stage, and N stage between the two groups(all P>0.05). The overall postoperative complication rate in the high-age group was significantly higher than that in the common elderly group(38.2% vs.24.7%, P=0.036); the medical complications were significantly increased in the high-age group(21.8% vs.10.9%, P=0.022), whereas the surgical complications did not increase significantly(25.5% vs.17.1%, P=0.135). Multivariate analysis revealed that the number of comorbidities ≥2( HR=2.502, 95% CI: 1.275-4.911, P=0.008), preoperative NRS 2002 scores ≥5( HR=2.714, 95% CI1.294-5.693, P=0.008), and preoperative ADL scores<100( HR=2.012, 95% CI1.010-4.009, P=0.047)were independent risk factors for medical complications.Additionally, ASA grade ≥ 3( HR=2.586, 95% CI: 1.444-4.632, P=0.001)and proximal or distal gastrectomy( HR=2.397, 95% CI: 1.237-4.574, P=0.009)were independent risk factors for surgical complications. Conclusions:The occurrence of postoperative medical complications in very elderly patients with gastric cancer undergoing radical surgery has increased, while the rate of surgical complications has not increased.Moreover, advanced age itself is not an independent risk factor for postoperative complications.More attention should be paid to medical complications, and the management of commodities and nutritional support should be strengthened during the perioperative period.

Objective To develop a three-compartment kinetic fatigue model for the isometric muscle endurance of the hip,knee,and ankle joints at 50％IPT(isometric peak torque),so as to provide a theoretical basis for simulation-based assessments and load evaluations in biomechanics and sports science.Methods The IPT of the hip,knee,and ankle joints was measured in 40 male university students.Isometric endurance tests were then performed on all three joints at 50％IPT until exhaustion.Electromyography data and endurance time(ET)of major lower limb muscles were collected concurrently.The differences between ETs predicted by models based on previously recommended F and R parameters and actual ETs were analyzed.Subsequently,experimental ETs were used in a grid search to optimize Fand R parameters,allowing for the development of an accurate three-compartment kinetic model.Results The ET of the hip and ankle joints was significantly longer than that of the knee joint(P＜0.001).Models using previously recommended Fand R parameters overestimated ET,with significantly higher predicted values than experimentally measured ET(P＜0.001),as well as elevated root mean squared error(RMSE)and mean relatvie error(MRE)values.The grid search successfully identified Fand R parameters for the three-compartment model in isometric endurance tests of lower limb joints,with no statistical difference between model-predicted ET and experimental ET(P＞0.05).Conclusions The developed model in this study can serve as an indirect measurement tool for evaluating load in similar activities.

BACKGROUND:Surface electromyography has been extensively utilized for monitoring muscle fatigue. However,traditional electromyographic metrics typically focus on individual muscles and fail to assess the variations in a muscle group during the fatigue process. OBJECTIVE:To establish a muscle functional network to extract complex network parameters and investigate the topological property changes of the muscle functional network under different levels of fatigue,aiming to provide theoretical and methodological foundations for fatigue monitoring and prevention. METHODS:Eleven participants performed single-leg leg press exercise at 50％ of one-repetition maximum until exhaustion. Simultaneously,electromyographic signals of seven muscles (rectus femoris,vastus lateralis,vastus medialis,biceps femoris,tibialis anterior,lateral gastrocnemius,and medial gastrocnemius),electrocardiographic signals,and Borg CR-10 scale scores were collected. The Borg CR-10 scale was used to categorize three fatigue stages:mild,moderate,and severe. Heart rate and heart rate variability were calculated to validate the effective division of fatigue stages. Using the coherence of muscle signals,a muscle functional network was constructed with the seven muscles as nodes,and four complex network parameters (clustering coefficient,average weighted degree,global efficiency,and eigenvector centrality) were extracted. Additionally,four electromyographic indices (root mean square,median frequency,instantaneous mean frequency,and co-activation ratio) were extracted and compared under the three levels of fatigue. RESULTS AND CONCLUSION:(1) Differences in heart rate and heart rate variability were observed across three fatigue stages,indicating the effectiveness of fatigue stage delineation. (2) Electromyographic indicators for different muscles under three levels of fatigue:root mean square and co-activation ratio showed no differences;however,median frequency exhibited robust fatigue trends in vastus lateralis,vastus medialis,and biceps femoris,while instantaneous mean frequency demonstrated robust fatigue trends in rectus femoris,vastus lateralis,vastus medialis,and biceps femoris. Instantaneous mean frequency outperformed median frequency and root mean square,yet all three indicators showed robust trends only for the major working muscle groups,unaffected by fatigue factors,unlike the co-activation ratio. (3) The connectivity strength between vastus lateralis and vastus medialis,vastus lateralis and biceps femoris,vastus lateralis and gastrocnemius medialis,and vastus medialis and biceps femoris gradually increased,showing significant differences in average weighted degree,clustering coefficient,and global efficiency post-fatigue,significantly correlated with fatigue levels. To conclude,changes in connectivity strength reflect the synergy and complementarity among muscles during fatigue. Clustering coefficient,average weighted degree,and global efficiency serve as fatigue markers reflecting overall muscle changes.

Objective:To propose a functional method for locating the shoulder joint center of rotation aimed at rapid estimation of the upper limb reachable domain envelope, thereby informing ergonomic design and task optimization.Methods:In March 2024, shoulder kinematics during gait were recorded from ten adults using a three-dimensional motion-capture system. Assuming the existence of a point near the glenohumeral joint that maintains a fixed spatial relationship to the humerus and the acromion, we estimated both static and dynamic centers of rotation. Localization accuracy was quantified by the standard deviation of distance residuals to upper-arm markers. Upper-limb joint angles and anthropometric parameters were modeled via regression; combined with maximal joint ranges of motion, these were used to infer the reachable domain envelope.Results:The static center of rotation was located approximately twenty-two millimeters medial to the acromial landmark in the coronal plane and thirty-seven millimeters inferior to it. The standard deviation of the residuals for the distances from the dynamic shoulder joint center of rotation to upper-arm markers averaged 1.02 mm, which was 47.42% lower than that of the static center of rotation and 66.56% lower than that of the acromion. Moreover, the trajectory of this dynamic center showed a strong correlation with upper-limb joint angles ( R2>0.7) . Conclusion:The proposed method enables rapid and accurate estimation of the upper limb reachable domain envelope to support ergonomic design and may help reduce the risk of work-related musculoskeletal disorders.

Migraine is a common neurological disorder with a complex pathogenesis that is currently not fully understood;however,the role of mitochondrial function in migraine pathogenesis has recently attracted widespread attention.This review considers the latest research progress on the relationship between mitochondrial dysfunction and migraine,including mitochondrial energy metabolism,oxidative stress,calcium homeostasis,and neuroinflammation.We introduce the epidemiological and clinical characteristics of migraine,and provide a detailed exploration of the key role of mitochondria in these processes.Mitochondrial dysfunction may lead to increased neuronal excitability,abnormal vasoconstriction,and inflammatory responses,thereby inducing migraine.Based on the evidence of mitochondrial involvement in the pathogenesis of migraine,we propose future research directions and potential treatment strategies,with the aim of providing new ideas for the prevention and treatment of migraine.

Objective To develop a three-compartment kinetic fatigue model for the isometric muscle endurance of the hip,knee,and ankle joints at 50％IPT(isometric peak torque),so as to provide a theoretical basis for simulation-based assessments and load evaluations in biomechanics and sports science.Methods The IPT of the hip,knee,and ankle joints was measured in 40 male university students.Isometric endurance tests were then performed on all three joints at 50％IPT until exhaustion.Electromyography data and endurance time(ET)of major lower limb muscles were collected concurrently.The differences between ETs predicted by models based on previously recommended F and R parameters and actual ETs were analyzed.Subsequently,experimental ETs were used in a grid search to optimize Fand R parameters,allowing for the development of an accurate three-compartment kinetic model.Results The ET of the hip and ankle joints was significantly longer than that of the knee joint(P＜0.001).Models using previously recommended Fand R parameters overestimated ET,with significantly higher predicted values than experimentally measured ET(P＜0.001),as well as elevated root mean squared error(RMSE)and mean relatvie error(MRE)values.The grid search successfully identified Fand R parameters for the three-compartment model in isometric endurance tests of lower limb joints,with no statistical difference between model-predicted ET and experimental ET(P＞0.05).Conclusions The developed model in this study can serve as an indirect measurement tool for evaluating load in similar activities.

BACKGROUND:Surface electromyography has been extensively utilized for monitoring muscle fatigue. However,traditional electromyographic metrics typically focus on individual muscles and fail to assess the variations in a muscle group during the fatigue process. OBJECTIVE:To establish a muscle functional network to extract complex network parameters and investigate the topological property changes of the muscle functional network under different levels of fatigue,aiming to provide theoretical and methodological foundations for fatigue monitoring and prevention. METHODS:Eleven participants performed single-leg leg press exercise at 50％ of one-repetition maximum until exhaustion. Simultaneously,electromyographic signals of seven muscles (rectus femoris,vastus lateralis,vastus medialis,biceps femoris,tibialis anterior,lateral gastrocnemius,and medial gastrocnemius),electrocardiographic signals,and Borg CR-10 scale scores were collected. The Borg CR-10 scale was used to categorize three fatigue stages:mild,moderate,and severe. Heart rate and heart rate variability were calculated to validate the effective division of fatigue stages. Using the coherence of muscle signals,a muscle functional network was constructed with the seven muscles as nodes,and four complex network parameters (clustering coefficient,average weighted degree,global efficiency,and eigenvector centrality) were extracted. Additionally,four electromyographic indices (root mean square,median frequency,instantaneous mean frequency,and co-activation ratio) were extracted and compared under the three levels of fatigue. RESULTS AND CONCLUSION:(1) Differences in heart rate and heart rate variability were observed across three fatigue stages,indicating the effectiveness of fatigue stage delineation. (2) Electromyographic indicators for different muscles under three levels of fatigue:root mean square and co-activation ratio showed no differences;however,median frequency exhibited robust fatigue trends in vastus lateralis,vastus medialis,and biceps femoris,while instantaneous mean frequency demonstrated robust fatigue trends in rectus femoris,vastus lateralis,vastus medialis,and biceps femoris. Instantaneous mean frequency outperformed median frequency and root mean square,yet all three indicators showed robust trends only for the major working muscle groups,unaffected by fatigue factors,unlike the co-activation ratio. (3) The connectivity strength between vastus lateralis and vastus medialis,vastus lateralis and biceps femoris,vastus lateralis and gastrocnemius medialis,and vastus medialis and biceps femoris gradually increased,showing significant differences in average weighted degree,clustering coefficient,and global efficiency post-fatigue,significantly correlated with fatigue levels. To conclude,changes in connectivity strength reflect the synergy and complementarity among muscles during fatigue. Clustering coefficient,average weighted degree,and global efficiency serve as fatigue markers reflecting overall muscle changes.