ObjectiveTo investigate the association of the single nucleotide polymorphism （SNP） of the insulin-like growth factor binding protein-3 （IGFBP3） gene at rs10225396 （A>G） locus with the susceptibility to hepatocellular carcinoma， as well as its potential molecular regulatory mechanisms， and to provide novel genetic biomarkers and a theoretical basis for early screening and precise targeted therapy for hepatocellular carcinoma. MethodsA total of 192 patients with hepatocellular carcinoma who were admitted to The Affiliated Hospital of Yanbian University and Yanbian Cancer Hospital from January 2009 to August 2016 were enrolled as experimental group， and 190 healthy individuals who underwent physical examination in Physical Examination Center of Yanbian Hospital during the same period of time were enrolled as control group. Peripheral blood samples were collected from all subjects， and after DNA was extracted from whole blood， the DNA samples meeting quality standards were sent to Beijing Genomics Institute Research Center Co.， Ltd.， for Mass ARRAY mass spectrometry， while genotyping was completed. The independent-samples t test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. A binary Logistic regression model was used to analyze the association of the SNP of the IGFBP3 gene at rs10225396 locus with the susceptibility to hepatocellular carcinoma， and odds ratio （OR） and 95% confidence interval （CI） were calculated to assess the risk of developing hepatocellular carcinoma in individuals carrying different genotypes. ResultsThere were two alleles （G and A） at the rs10225396 locus of the IGFBP3 gene， yielding the three genotypes of AA， AG， and GG， and its genotype distribution was consistent with the Hardy-Weinberg equilibrium （χ²=0.072， P=0.789）. The stratified genetic analysis showed that carriers of the IGFBP3 rs10225396 AA genotype had a significant increased risk of hepatocellular carcinoma among individuals of age <63 years， male sex， smoking history， drinking history， and the Chinese Korean population （all P<0.001）. The binary Logistic regression analysis showed that after adjustment for related risk factors in the codominant model， the population with genotype AG and GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）， and in the dominant model， the population with genotype AG+GG had a significant reduction in the risk of hepatocellular carcinoma compared with the population with genotype AA （P<0.001）. ConclusionThrough a genotyping analysis of hepatocellular carcinoma patients and healthy individuals in Yanbian Korean Autonomous Prefecture of Jilin Province， China， this study shows that genotype AA at rs10225396 locus of the IGFBP3 gene is significantly associated with the susceptibility to hepatocellular carcinoma， and this genotype can significantly increase the risk of developing hepatocellular carcinoma with the presence of specific risk factors， which provides a potential genetic marker for early screening and precise treatment of hepatocellular carcinoma.

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.

Objective: To study the effect of metformin sensitizing pancreatic cancer cells with radiotherapy, with a focus on elucidating the underlying mechanisms of radiotherapy resistance. In particular, the role of the PERK/P-eIF2/ATF4 signaling pathway in mediating these effects was preliminarily explored. Methods : Pancreatic cancer cell lines(PANC-1 and PANC-2) were categorized into control, radiotherapy, and drug treatment groups. Following the respective treatments, cell proliferation inhibition was assessed using the CCK-8 assay, colony formation assays, and cell death staining. Senescence was quantified by β-galactosidase(SA-β-Gal) staining. The expression of cell cycle regulators(P21, P16, γ-H2AX), apoptosis markers(Bax, Bcl-2, Cleaved caspase-3), and pathway-related proteins(PERK, P-eIF2, ATF4) was evaluated by Western blot and immunofluorescence. To further investigate the role of the PERK/P-eIF2/ATF4 axis in metformin-mediated modulation of pancreatic cancer cell senescence and radiosensitization, selective inhibitors(GSK2606414) and agonists(MK-28) of PERK were employed. Results : Radiotherapy markedly upregulated senescence-associated markers(P21, P16, γ-H2AX, and β-galactosidase activity) in pancreatic cancer cells. Senescent cells exhibited enhanced proliferative activity and increased tumor volume both in vitro and in vivo. Metformin mitigated radiotherapy-induced senescence by reducing the expression of senescence markers and significantly suppressing the clonogenic and proliferative capacity of treated cells. Mechanistically, radiotherapy activated the PERK signaling pathway, leading to increased expression of PERK, P-eIF2, and ATF4, thereby driving cellular senescence. Pharmacological inhibition of PERK reduced β-galactosidase activity, while PERK activation further promoted the expression of senescence-associated proteins—an effect that was reversed by metformin. Conclusion Metformin inhibits the activation of the PERK/P-eIF2/ATF4 signaling pathway in pancreatic cancer cells following radiotherapy, thereby delaying cellular senescence and reducing the associated radiotherapy resistance of senescent cells. This modulation contributes to the sensitization of pancreatic cancer cells to radiotherapy.

The escalating phenomenon of global population aging is posing multi-dimensional challenges to society, the economy and medical healthcare system.Among the significant health threats to the elderly population are cardiovascular diseases(CVD)and cognitive frailty(CF), both of which profoundly affect the quality of life and increase the risks of adverse health outcomes, including disability, hospitalization, and death.The concurrent presence of CVD and CF in elderly patients is prevalent, as these conditions share many common risk factors and underlying pathophysiological mechanisms, such as atherosclerosis, microcirculation dysfunction, and inflammation, which interact to perpetuate a vicious cycle.Notably, CF exhibits a certain degree of reversibility; thus, the implementation of a diagnosis and treatment paradigm that incorporates "comprehensive geriatric assessment and geriatric interdisciplinary teams" should be established as a conventional management strategy for elderly patients affected by both CVD and CF.Cognitive digital therapeutics, along with personalized exercise prescriptions based on cardiopulmonary exercise tests, may represent more appropriate precision interventions for these patients.Consequently, there is a necessity for further in-depth research in this area moving forward.

During transfer tasks, the dual-arm nursing-care robot require a human-robot mechanics model to determine the balance region to support the patient safely and stably. Previous studies utilized human-robot two-dimensional static equilibrium models, ignoring the human body volume and muscle torques, which decreased model accuracy and confined the robot ability to adjust the patient's posture in three-dimensional spatial. Therefore, this study proposes a three-dimensional spatial mechanics modeling method based on individualized human musculoskeletal multibody dynamics. Firstly, based on the mechanical features of dual-arm support, this study constructed a foundational three-dimensional human-robot mechanics model including body posture, contact position and body force. With the computed tomography data from subjects, a three-dimensional femur-pelvis-sacrum model was reconstructed, and the individualized musculoskeletal dynamics was analyzed using the ergonomics software, which derived the human joint forces and completed the mechanic model. Then, this study established a dual-arm robot transfer platform to conduct subject transfer experiments, showing that the constructed mechanics model possessed higher accuracy than previous methods. In summary, this study provides a three-dimensional human-robot mechanics model adapting to individual transfers, which has potential application in various scenarios such as nursing-care and rehabilitating robots.
Humans ; Robotics ; Biomechanical Phenomena ; Posture ; Imaging, Three-Dimensional ; Nursing Care

Objective To explore the motor coordination characteristics of the attack leg of the athletes under scoring actions in the front roundhouse kick of competitive taekwondo,and provide a theoretical basis for coaches to formulate precise training strategies in stages and segments so as to enhance the efficiency and success rate of the athletes' movements.Methods Kinematic data and surface electromyography signals were collected from 15 elite Taekwondo athletes during different phases of the front roundhouse kick.The continuous relative phase(CRP)method was used to calculate the joint coordination and variability of continuous relative phase(VCRP),while non-negative matrix factorization and k-means clustering were used to analyze muscle synergy characteristics.Results The coupling of the neural launch phase was dominated by knee-ankle coupling in coronal axis and hip-ankle coupling in sagittal axis.The coupling of the kicking phase was dominated by hip-knee,hip-ankle in coronal axis,and knee-ankle coupling in vertical axis.The coupling of the recovery phase was dominated by hip-knee,hip-ankle coupling in coronal axis,and knee-ankle coupling in sagittal axis.These coupling relationships remained relatively stable around 0 rad.Approximately 80.0％VCRP remained stable across all phases,with minor fluctuations occurring at phase transitions.A total of 4,5,and 4 muscle synergy clusters were identified in neural launch,kicking,recovery phases,respectively.There were significant differences in the mean gap values among phases(P＜0.001).However,there were no significant differences in the mean sparsity values among phases(P＞0.05).Some muscle synergies were shared across phases,while others differentiated to form phase-specific coordination patterns.Conclusions Joint coordination in each phase exhibited 1-3 primary stable patterns with flexibility during transitions.Muscle coordination was dynamically adjusted throughout the motion,and a general muscle synergy pattern functioned consistently across different phases,whereas a differentiated muscle synergy pattern fulfilled the phase-specific functional demands.The neural launch and kicking phases should be focused on during training,with the emphasis on controling over critical points to optimize performance.

Objective To explore the motor coordination characteristics of the attack leg of the athletes under scoring actions in the front roundhouse kick of competitive taekwondo,and provide a theoretical basis for coaches to formulate precise training strategies in stages and segments so as to enhance the efficiency and success rate of the athletes' movements.Methods Kinematic data and surface electromyography signals were collected from 15 elite Taekwondo athletes during different phases of the front roundhouse kick.The continuous relative phase(CRP)method was used to calculate the joint coordination and variability of continuous relative phase(VCRP),while non-negative matrix factorization and k-means clustering were used to analyze muscle synergy characteristics.Results The coupling of the neural launch phase was dominated by knee-ankle coupling in coronal axis and hip-ankle coupling in sagittal axis.The coupling of the kicking phase was dominated by hip-knee,hip-ankle in coronal axis,and knee-ankle coupling in vertical axis.The coupling of the recovery phase was dominated by hip-knee,hip-ankle coupling in coronal axis,and knee-ankle coupling in sagittal axis.These coupling relationships remained relatively stable around 0 rad.Approximately 80.0％VCRP remained stable across all phases,with minor fluctuations occurring at phase transitions.A total of 4,5,and 4 muscle synergy clusters were identified in neural launch,kicking,recovery phases,respectively.There were significant differences in the mean gap values among phases(P＜0.001).However,there were no significant differences in the mean sparsity values among phases(P＞0.05).Some muscle synergies were shared across phases,while others differentiated to form phase-specific coordination patterns.Conclusions Joint coordination in each phase exhibited 1-3 primary stable patterns with flexibility during transitions.Muscle coordination was dynamically adjusted throughout the motion,and a general muscle synergy pattern functioned consistently across different phases,whereas a differentiated muscle synergy pattern fulfilled the phase-specific functional demands.The neural launch and kicking phases should be focused on during training,with the emphasis on controling over critical points to optimize performance.

The escalating phenomenon of global population aging is posing multi-dimensional challenges to society, the economy and medical healthcare system.Among the significant health threats to the elderly population are cardiovascular diseases(CVD)and cognitive frailty(CF), both of which profoundly affect the quality of life and increase the risks of adverse health outcomes, including disability, hospitalization, and death.The concurrent presence of CVD and CF in elderly patients is prevalent, as these conditions share many common risk factors and underlying pathophysiological mechanisms, such as atherosclerosis, microcirculation dysfunction, and inflammation, which interact to perpetuate a vicious cycle.Notably, CF exhibits a certain degree of reversibility; thus, the implementation of a diagnosis and treatment paradigm that incorporates "comprehensive geriatric assessment and geriatric interdisciplinary teams" should be established as a conventional management strategy for elderly patients affected by both CVD and CF.Cognitive digital therapeutics, along with personalized exercise prescriptions based on cardiopulmonary exercise tests, may represent more appropriate precision interventions for these patients.Consequently, there is a necessity for further in-depth research in this area moving forward.

Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.

BACKGROUND:Swimming is an important non-pharmacological treatment for knee osteoarthritis,which can effectively alleviate the disease.However,the effect and mechanism of swimming on senile knee osteoarthritis are still unclear. OBJECTIVE:To investigate the effect of swimming exercise on the articular cartilage of aged mice with knee osteoarthritis. METHODS:Six 3-month-old male C57BL/6 mice were selected as the young group,and twelve 18-month-old male C57BL/6 mice were randomized into the aged group and the swimming group,with six mice in each group.Mice in the swimming group received adaptive swimming for 1 week and formal swimming for 8 weeks.After the intervention,stride length analysis and sampling were performed in each group.The total number of leukocytes and lymphocytes in peripheral blood was detected by blood routine examinations.The morphology of the articular cartilage was observed by hematoxylin-eosin and safranin O-fast green staining.Chondrocyte counts and the modified Mankin's score were used to evaluate the degree of articular cartilage damage.The protein and mRNA expressions of type Ⅱ collagen,aggrecan and matrix metalloproteinase 13 in articular cartilage were detected by immunohistochemical staining and RT-qPCR. RESULTS AND CONCLUSION:Compared with the young group,the mice in the aged group showed significantly decreased stride length(P＜0.05),significantly increased numbers of peripheral leukocytes and lymphocytes(P＜0.05),significantly decreased count of chondrocytes(P＜0.05),significantly increased modified Mankin's score(P＜0.05),significantly decreased protein and mRNA expression of type Ⅱ collagen and aggreca(P＜0.05),and significantly increased matrix metalloproteinase 13 expression(P＜0.05).Moreover,hematoxylin-eosin and safranin O-fast green staining showed the uneven surface of the articular cartilage,abnormal chondrocytes,and proteoglycan loss in the aged group.Compared with the aged group,swimming exercise significantly improved the stride length of mice(P＜0.05),decreased the count of peripheral blood lymphocytes(P＜0.05),increased the count of chondrocytes(P＜0.05),decreased the modified Mankin's score(P＜0.05),increased the protein and mRNA expression of type Ⅱ collagen and aggrecan(P＜0.05),and decreased the expression of matrix metalloproteinase 13(P＜0.05).Hematoxylin-eosin and safranin O-fast green staining showed that the articular surface of mice in the swimming group was smooth,chondrocytes were normal,and proteoglycan loss was less.All these findings indicate that swimming exercise can reduce the number of inflammatory cells in the blood of aged mice,improve articular chondrocytes,matrix composition and cartilage tissue morphology;thus,it has a protective effect on the cartilage of aged mice with knee osteoarthritis.