Objective:To investigate the effect of asparagine synthetase (ASNS) knockdown on the senescence of retinal pigment epithelial (RPE) cells and its potential molecular mechanism.Methods:Human ARPE-19 RPE cells were divided into four groups: control group, short hairpin RNA targeting ASNS (shASNS) group, control+ (Janus kinase) JAK inhibitor group, and shASNS+ JAK inhibitor group, which were treated with short hairpin RNA control+ dimethyl sulfoxide (DMSO), shASNS+ DMSO, control+ JAK inhibitor and shASNS+ JAK inhibitor for 12 hours, respectively.An RPE cell senescence model was established by cell treatment with 500 μmol/L H 2O 2 for 24 hours.The mRNA and protein levels of ASNS and JAK were detected by real-time fluorescent quantitative PCR and Western blot, respectively.Reactive oxygen species (ROS) level within cells was measured using a kit.Cell cycle phase distribution and apoptosis rates were analyzed by flow cytometry.Cell viability from day 1 to day 5 of culturing was assessed via MTT assay.Senescent cell ratio was determined by β-galactosidase staining.Cellular damage was evaluated via immunofluorescence staining.Senescence-associated proteins (p16, pRb), and RPE markers (KRT18, CTNNB1, TJP1, BEST1) were quantified by Western blot. Results:Compared with the control group, mRNA and protein expression levels of ASNS and JAK were significantly reduced in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor groups (all P<0.05).DCFH-DA staining revealed significantly lower ROS level in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group than in the control group (all P<0.05).Flow cytometry showed that there were more G2-phase cells and significantly reduced apoptosis rate in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group (all P<0.01).MTT assay indicated higher cell viability at all time points in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group, with statistically significant differences (all P<0.01).β-galactosidase-positive cell ratios in the shASNS, control+ JAK inhibitor, and shASNS+ JAK inhibitor groups were (42.36±1.28)%, (43.20±1.89)%, (25.97±1.13)%, respectively, which were significantly lower than (52.25±0.64)% in the control group (all P<0.001).p16 and pRb protein expression were decreased and γ-H2AX fluorescence intensity was attenuated in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group (all P<0.01).KRT18 and CTNNB1 expressions were upregulated, whereas TJP1 and BEST1 were downregulated in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group (all P<0.05).The shASNS+ JAK inhibitor group exhibited higher KRT18 and CTNNB1 expressions and lower TJP1 and BEST1 expressions than the shASNS and control+ JAK inhibitor groups (all P<0.05). Conclusions:ASNS knockdown can promote RPE cell proliferation, mitigate cellular damage, and delay senescence by suppressing the JAK pathway.

Objective Wearable devices refer to a class of monitoring devices that can be tightly integrated with the human body and are designed to continuously monitor individual's activity without impeding or restricting the user's normal activities in the process. With the rapid advancement of chips, sensors, and artificial intelligence technologies, such devices have been widely used for patients with cardiovascular diseases who require continuous health monitoring. These patients require continuous monitoring of a number of physiological indicators to assess disease progression, treatment efficacy, and recovery in the early stages of the disease, during the treatment, and in the recovery period. Traditional monitoring methods require patients to see a doctor on a regular basis with the help of fixed devices and analysis by doctors, which not only increases the financial burden of patients, but also consumes medical resources and time. However, wearable devices can collect data in real time and transmit it directly to doctors via the network, thus providing an efficient and cost-effective monitoring solution for patients. In this paper, we will review the applications, advantages and challenges of wearable devices in the treatment of cardiovascular diseases, as well as the outlook for their future applications.

BACKGROUND: Without timely and effective rehabilitation, hearing loss may profoundly affect human life quality. China has a large population of hearing-impaired individuals, which imposes a heavy health burden on society. Moreover, this population is projected to increase rapidly owing to China's aging society. METHODS: We used data from a population-representative epidemiological investigation of hearing loss and ear diseases in four Chinese provinces. We estimated the national prevalence using multiple linear regression of the age-group proportions and prevalence in 31 provinces with clustering analysis. We used years lived with disability (YLDs) to analyze the disease burden and forecasted the prevalence of hearing loss by 2060 in China. RESULTS: An estimated 115 million people had moderate-to-complete hearing loss in 2015 across the 31 provinces of China (8.4% of 1.37 billion people). Of these, 85.7% were older than age 50 years (99 million people) and 2.4% were younger than 20 years old (2.8 million people). Of all YLDs attributable to hearing loss, 68.9% were attributable to moderate-to-complete cases. By 2060, a projected 242 million people in China will have moderate-to-complete hearing loss, a 110.0% increase from 2015. CONCLUSIONS The hearing loss prevalence in China is high. Population aging and socioeconomic factors substantially affect the prevalence and severity of hearing loss and the disease burden. The prevalence and severity of hearing loss are unevenly distributed across different provinces. Future public health policies should take these trends and regional variations into account.
Humans ; China/epidemiology* ; Hearing Loss/epidemiology* ; Prevalence ; Middle Aged ; Male ; Female ; Adult ; Aged ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Aged, 80 and over ; Cost of Illness

Objective To conduct a scoping review of the application of gamification programs in exercise rehabilitation for knee osteoarthritis,examining the application carriers,game content,outcome indicators,measurement tools,and application effects of gamification programs,to provide references for future practice and related research in this field.Methods The search was conducted in PubMed,Web of Science,Cochrane Library,Scopus,CIN AHL,China National Knowledge Infrastructure,CNKI,and Wanfang Data from their inception to December 28,2024.The included studies were summarized and analyzed.Results A total of 28 studies were included in the review.The game carriers encompassed virtual reality technology,sensor devices,and mobile applications.The game content covered interactive motion games,aerobic exercises,and goal-motivated games.Outcome indicators included functional performance,physical activity,pain,psychological and health status,and user experience.Gamification programs were found to effectively enhance user engagement,improve physical function,reduce negative emotions,and improve quality of life.However,there remains controversy regarding their efficacy in pain relief.Conclusion Gamification programs have shown positive effects in exercise rehabilitation for knee osteoarthritis.Future efforts should focus on developing gamification programs that are culturally appropriate for China,creating"digital therapeutics",continuously updating systems,conducting economic evaluations,and ensuring digital equity to enhance patients'rehabilitation experiences and improve health outcomes.

Objective:To investigate the effect of asparagine synthetase (ASNS) knockdown on the senescence of retinal pigment epithelial (RPE) cells and its potential molecular mechanism.Methods:Human ARPE-19 RPE cells were divided into four groups: control group, short hairpin RNA targeting ASNS (shASNS) group, control+ (Janus kinase) JAK inhibitor group, and shASNS+ JAK inhibitor group, which were treated with short hairpin RNA control+ dimethyl sulfoxide (DMSO), shASNS+ DMSO, control+ JAK inhibitor and shASNS+ JAK inhibitor for 12 hours, respectively.An RPE cell senescence model was established by cell treatment with 500 μmol/L H 2O 2 for 24 hours.The mRNA and protein levels of ASNS and JAK were detected by real-time fluorescent quantitative PCR and Western blot, respectively.Reactive oxygen species (ROS) level within cells was measured using a kit.Cell cycle phase distribution and apoptosis rates were analyzed by flow cytometry.Cell viability from day 1 to day 5 of culturing was assessed via MTT assay.Senescent cell ratio was determined by β-galactosidase staining.Cellular damage was evaluated via immunofluorescence staining.Senescence-associated proteins (p16, pRb), and RPE markers (KRT18, CTNNB1, TJP1, BEST1) were quantified by Western blot. Results:Compared with the control group, mRNA and protein expression levels of ASNS and JAK were significantly reduced in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor groups (all P<0.05).DCFH-DA staining revealed significantly lower ROS level in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group than in the control group (all P<0.05).Flow cytometry showed that there were more G2-phase cells and significantly reduced apoptosis rate in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group (all P<0.01).MTT assay indicated higher cell viability at all time points in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group, with statistically significant differences (all P<0.01).β-galactosidase-positive cell ratios in the shASNS, control+ JAK inhibitor, and shASNS+ JAK inhibitor groups were (42.36±1.28)%, (43.20±1.89)%, (25.97±1.13)%, respectively, which were significantly lower than (52.25±0.64)% in the control group (all P<0.001).p16 and pRb protein expression were decreased and γ-H2AX fluorescence intensity was attenuated in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group (all P<0.01).KRT18 and CTNNB1 expressions were upregulated, whereas TJP1 and BEST1 were downregulated in the shASNS group, control+ JAK inhibitor group, and shASNS+ JAK inhibitor group compared with the control group (all P<0.05).The shASNS+ JAK inhibitor group exhibited higher KRT18 and CTNNB1 expressions and lower TJP1 and BEST1 expressions than the shASNS and control+ JAK inhibitor groups (all P<0.05). Conclusions:ASNS knockdown can promote RPE cell proliferation, mitigate cellular damage, and delay senescence by suppressing the JAK pathway.

Objective To conduct a scoping review of the application of gamification programs in exercise rehabilitation for knee osteoarthritis,examining the application carriers,game content,outcome indicators,measurement tools,and application effects of gamification programs,to provide references for future practice and related research in this field.Methods The search was conducted in PubMed,Web of Science,Cochrane Library,Scopus,CIN AHL,China National Knowledge Infrastructure,CNKI,and Wanfang Data from their inception to December 28,2024.The included studies were summarized and analyzed.Results A total of 28 studies were included in the review.The game carriers encompassed virtual reality technology,sensor devices,and mobile applications.The game content covered interactive motion games,aerobic exercises,and goal-motivated games.Outcome indicators included functional performance,physical activity,pain,psychological and health status,and user experience.Gamification programs were found to effectively enhance user engagement,improve physical function,reduce negative emotions,and improve quality of life.However,there remains controversy regarding their efficacy in pain relief.Conclusion Gamification programs have shown positive effects in exercise rehabilitation for knee osteoarthritis.Future efforts should focus on developing gamification programs that are culturally appropriate for China,creating"digital therapeutics",continuously updating systems,conducting economic evaluations,and ensuring digital equity to enhance patients'rehabilitation experiences and improve health outcomes.

Objective:To explore the inhibitory effect of curcumin on the malignant biological behavior of uveal melanoma (UM) and its possible mechanism.Methods:M23 cells were cultured in curcumin medium with different concentrations (0, 20, 40 and 80 μmol/L) for 48 hours, respectively.The morphological changes of cells were observed under an inverted microscope.The cell survival rate was detected by the cell counting kit-8 (CCK-8) method.The apoptosis, colony formation, migration and invasion of cells were detected by flow cytometry, plate clone formation experiment, cell scratch experiment and Transwell assay, respectively.The relative expressions of genes related to Wnt/β-catenin pathway, c-Myc, Cyclin D1, Survivin and matrix metallo proteinase 9 ( MMP-9) mRNA in cells were detected by real-time fluorescence quantitative PCR.The relative expressions of proteins related to Wnt/β-catenin pathway, c-Myc, Cyclin D1, Survivin, MMP-9 and β-catenin, glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β (p-GSK-3β) and axis inhibition protein 2 (Axin2) proteins were detected by Western blot.Another 20 female BALB/c mice were selected and injected with M23 cell suspension under the subcutaneous fat pad in the left posterior abdomen to establish the in vivo M23 transplanted tumor model.The mice successfully modeled were randomly divided into model group, low-dose curcumin group, medium-dose curcumin group and high-dose curcumin group according to the random number table method, which was intraperitoneally injected with 0, 10, 20 and 40 mg/kg curcumin physiological saline solution respectively.After a continuous injection for 30 days, the subcutaneous tumor was stripped and weighed.The animal experiment process followed the 3Rs principle of animal research and was approved by the Laboratory Animal Ethics Committee of Inner Mongolia Baotou Steel Hospital (No.2021MER-023). Results:The cell survival rate, the number of colony formation, the apoptosis rate, the cell invasion rate and the cell migration rate were (100.00±0.00)%, 128.67±9.18, (1.33±0.29)%, (89.76±4.57)% and 148.33±8.18 in 0 μmol/L curcumin group, (83.78±4.59)%, 100.33±8.73, (14.53±2.04)%, (65.43±3.70)% and 125.33±7.41 in 20 μmol/L curcumin group, (66.09±3.92)%, 58.67±6.55, (27.23±3.56)%, (34.83±2.19)% and 73.67±6.34 in 40 μmol/L curcumin group, and (47.16±3.63)%, 31.67±4.92, (44.73±4.36)%, (18.82±1.99)% and 45.67±5.31 in 80 μmol/L curcumin group.There were statistically significant differences in the survival rate, colony formation number, cell apoptosis rate, migration rate and invasion rate of M23 cells among the four groups ( F=125.321, 97.941, 72.516, 277.097, 139.006; all at P<0.001). With the increase of curcumin concentration, the cell survival rate, colony formation number, cell migration rate and cell invasion number decreased obviously, and the cell apoptosis rate increased obviously, and the pairwise comparisons showed significant differences (all at P<0.05). With the increase of curcumin concentration, the relative expression levels of c-Myc, Cyclin D1, Survivin, MMP-9 mRNA and proteins, β-catenin and p-GSK-3β proteins decreased significantly, while the relative expression level of Axin2 protein increased significantly, showing significant differences in pairwise comparisons (all at P<0.05). The tumor tissue weight of mice decreased with the increase of curcumin dosage, and the pairwise comparisons were statistically significant (all at P<0.05). Conclusions:Curcumin can inhibit the proliferation, migration, invasion and other malignant biological behaviors of UM M23 cells, inhibit tumor growth and promote cell apoptosis.Its mechanism may be related to blocking the activation of Wnt/β-catenin pathway.

Objective To explore the predictive value of systolic pulmonary artery pressure (SPAP) on autonomic nerve excitation in patients with valvular disease, so as to provide reference for the formulation of clinical intervention plans. Methods The clinical data of patients with valvular disease who received surgical treatment in the General Hospital of Northern Theater Command from August 28, 2020 to February 3, 2021 were prospectively collected. According to the standard deviation of normal-to-normal R-R intervals (SDNN) of the heart rate variability (HRV) of the long-range dynamic electrocardiogram (ECG) 7 days before the operation, the patients were divided into three groups: a sympathetic dominant (SE) group (SDNN≤50 ms), a balance group (50 ms

Objective To study the antioxidant activity and free radical scavenging kinetics of Chrysanthemi flos stems and leaves,and online screen the active components related to free radical scavenging.Methods Using DPPH method and ABTS method the antioxidant activity of extracts from Chrysanthemi flos stems and leaves was observed,and the effects of different influencing factors,such as drug concentration,reaction temperature and reaction time on free radical scavenging rate were compared,the half scavenging rate(IC50)was determined.The flavonoids,such as luteolin glucuronic acid,luteolin,and caffeic acid,phenolic acids such as chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,isochlorogenic acid A,B,and C in the samples before and after the reaction were chosen as indexes,and their contents were determined by HPLC.Results The drug concentration,reaction temperature and reaction time could affect the scavenging rate of DPPH free radical and ABTS.The IC50 of DPPH and ABTS were 0.395 mg·mL-1 and 2.039 mg·mL-1 respectively.After reaction with DPPH and ABTS,the contents of the analytes above all decreased significantly,which suggested that,the components above might be the antioxidant components in Chrysanthemi flos stems and leaves.Conclusions Chrysanthemi flos Stems and leaves have good free radical scavenging activity.In this study,the kinetic characteristics of scavenging DPPH and ABTS free radicals in Chrysanthemi flos stems and leaves were preliminarily clarified,and the active components were found out.It provides an experimental basis for the future comprehensive development of Chrysanthemi flos stems and leaves.