Background High-speed train engineers' lower extremities are constrained by compulsive vigilance pedal tasks and limited space beneath the control console during driving. Shifts in alertness triggered by running route observation may share the same mental resource required by moderate-to-low physical exertion. Current research on improving cab design and maintaining optimal on-duty attention allocation remains limited. Objective To examine variations in lower extremity muscle load, gaze-tracking behavior, and driving performance under various combinations of vigilance pedal positions and route scenarios during simulated high-speed train tasks. To identify optimal working condition combinations that promote level and variety of physical activity and facilitate rational attention allocation. Methods A 4×2 within-subjects design were employed (4 vigilance pedal position profiles: knee front, side, and any; 2 route scenarios: monotonous and complex). Nine male college volunteers were recruited as simulated drivers to perform designated interval driving tasks. Surface electromyography and eye tracking were used to assess leg muscle load and gaze behavior respectively. Task performance and subjective fatigue were recorded. Results In all simulation driving tasks, skeletal muscle loads were low with the percentage of maximum voluntary contraction (%MVC) at approximately 4%. No fatigue tendencies were observed within single trial blocks (7 min), and the subjective fatigue ratings remained relatively low. While the activation of the dominant-side tibialis anterior was higher for the knee pedal than for the front (%MVC: 3.7% ± 3.13% vs. 1.08% ± 0.72%) or the side pedals (%MVC: 3.7% ± 3.13% vs. 1.4% ± 0.77%). The activation level of the dominant-side gastrocnemius was higher for the knee pedal than for the other three pedal profiles. For the any pedal condition, the intercept of the instantaneous median frequency curve for the dominant-side rectus femoris was lower in the monotonous route than in the complex route [(111.18 ± 35.78) Hz vs. (153.33 ± 39.12) Hz]. Among eye-tracking metrics, total fixations were higher during knee-level pedaling than side pedaling, while more saccades were recorded in monotonous routes than in complex ones. Regarding task performance, the any pedal yielded fewer missed signals than the front pedal, with 2/3 and 1/3 of participants preferring the front and knee pedals, respectively. The activation levels of the dominant tibialis anterior and dominant gastrocnemius muscles during the knee pedal × complex route combination were higher than any combination involving the front pedal. No statistically significant effect of pedal position or route scenario was found on other indicators. Conclusion The combination of knee pedal and complex route provides an optimal working setting for maximizing leg muscle mobility without compromising attention allocation or driving performance. It is recommended that train engineers modulate attention during monotonous routes to avoid emotional tension and increased muscle strain caused by over-monitoring. Given the ergonomic characteristics of high cognitive load, low physical exertion levels, and highly restricted lower limb mobility among high-speed train engineers, future cab designs should consider incorporating knee-level vigilance pedal and adjust safety alertness rules to allow reset via either front or knee pedal.

Background High-speed train engineers' lower extremities are constrained by compulsive vigilance pedal tasks and limited space beneath the control console during driving. Shifts in alertness triggered by running route observation may share the same mental resource required by moderate-to-low physical exertion. Current research on improving cab design and maintaining optimal on-duty attention allocation remains limited. Objective To examine variations in lower extremity muscle load, gaze-tracking behavior, and driving performance under various combinations of vigilance pedal positions and route scenarios during simulated high-speed train tasks. To identify optimal working condition combinations that promote level and variety of physical activity and facilitate rational attention allocation. Methods A 4×2 within-subjects design were employed (4 vigilance pedal position profiles: knee front, side, and any; 2 route scenarios: monotonous and complex). Nine male college volunteers were recruited as simulated drivers to perform designated interval driving tasks. Surface electromyography and eye tracking were used to assess leg muscle load and gaze behavior respectively. Task performance and subjective fatigue were recorded. Results In all simulation driving tasks, skeletal muscle loads were low with the percentage of maximum voluntary contraction (%MVC) at approximately 4%. No fatigue tendencies were observed within single trial blocks (7 min), and the subjective fatigue ratings remained relatively low. While the activation of the dominant-side tibialis anterior was higher for the knee pedal than for the front (%MVC: 3.7% ± 3.13% vs. 1.08% ± 0.72%) or the side pedals (%MVC: 3.7% ± 3.13% vs. 1.4% ± 0.77%). The activation level of the dominant-side gastrocnemius was higher for the knee pedal than for the other three pedal profiles. For the any pedal condition, the intercept of the instantaneous median frequency curve for the dominant-side rectus femoris was lower in the monotonous route than in the complex route [(111.18 ± 35.78) Hz vs. (153.33 ± 39.12) Hz]. Among eye-tracking metrics, total fixations were higher during knee-level pedaling than side pedaling, while more saccades were recorded in monotonous routes than in complex ones. Regarding task performance, the any pedal yielded fewer missed signals than the front pedal, with 2/3 and 1/3 of participants preferring the front and knee pedals, respectively. The activation levels of the dominant tibialis anterior and dominant gastrocnemius muscles during the knee pedal × complex route combination were higher than any combination involving the front pedal. No statistically significant effect of pedal position or route scenario was found on other indicators. Conclusion The combination of knee pedal and complex route provides an optimal working setting for maximizing leg muscle mobility without compromising attention allocation or driving performance. It is recommended that train engineers modulate attention during monotonous routes to avoid emotional tension and increased muscle strain caused by over-monitoring. Given the ergonomic characteristics of high cognitive load, low physical exertion levels, and highly restricted lower limb mobility among high-speed train engineers, future cab designs should consider incorporating knee-level vigilance pedal and adjust safety alertness rules to allow reset via either front or knee pedal.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

[Purpose]To analyze the epidemiology and disease burden of gastric cancer in China,Japan and Republic of Korea from 1990 to 2021 and to predict changing trends from 2022 to 2031.[Methods]Data were obtained from the Global Burden of Disease(GBD)database.Age-stan-dardized incidence rate(ASIR),age-standardized mortality rate(ASMR),crude incidence rate(CIR),crude mortality rate(CMR),and disability-adjusted life years(DALY)rate for China,Japan and Republic of Korea from 1990 to 2021 were analyzed.Joinpoint regression software was used to analyze trends and calculate annual percentage changes.The autoregressive integrated moving average(ARIMA)model was applied to predict incidence and mortality from 2022 to 2031.[Results]In 2021,China had 611 799 new gastric cancer cases and 445 013 deaths,with an ASIR of 29.05/105 and an ASMR of 21.51/105,both significantly higher than those in Japan and Republic of Korea.Among men in China,both the ASIR(44.48/105)and ASMR(32.61/105)were the highest among the three countries,exceeding those in Japan(38.77/105,20.26/105)and Re-public of Korea(38.98/105,20.50/105).Among women,China had the highest number of new cases,but its ASIR(15.23/105)was slightly lower than Republic of Korea's(15.57/105)and higher than Japan's(14.66/105).However,China's ASMR among women(12.02/105)remained significantly higher than Japan's(7.64/105)and Republic of Korea's(8.08/105).From 1990 to 2021,ASIR,ASMR and DALY rates for gastric cancer declined in all three countries,but the reduction in China was significantly smaller than that in Japan and Republic of Korea,with Republic of Korea showing the steepest declines across all indicators.ARIMA model predictions indicated significant differences in disease burden among the three countries from 2022 to 2031.ASIR is projected to continue declining in China and Republic of Korea,reaching 22.87/105 and 12.45/105,respectively by 2031,while in Japan it is predicted to rise to 26.55/105.ASMR is projected to decline in all three countries,reaching 13.71/105(China),10.44/105(Japan),and 9.08/105(Republic of Korea)in 2031.[Conclusion]Among China,Japan and Republic of Korea,China had the highest ASIR and ASMR of gastric cancer in 2021.Moreover,from 1990 to 2021,the reductions in ASIR,ASMR and DALY rates for gastric cancer were the smallest in China compared to Japan and Republic of Korea.These findings suggest that the disease burden of gastric cancer remains substantial in China,high-lighting the need for increased efforts in gastric cancer screening and early diagnosis and treatment.

Objective To analyze the clinical research literature of in vitro fertilization and embryo transfer(IVF-ET)failure,and summarize the traditional Chinese medicine(TCM)syndromes and syndrome elements,so as to provide theoretical basis for TCM syndrome differentiation and treatment of IVF-ET failure.Methods Using"in vitro fertilization and embryo transfer""IVF-ET"and"embryo transfer failure"as search terms,the literature related to TCM that had appeared in CNKI and Wanfang Data Knowledge Service Platform were searched since these database was constructed.After excluding irrelevant literature,statistical analysis was performed on the frequency and frequency of symptoms and signs.Results Kidney Yang deficiency,kidney deficiency,blood stasis,kidney Yin deficiency and liver qi stagnation were the common syndroms of failure.The disease location with high frequency of syndrome elements was kidney,and the disease was blood stasis.Conclusion Kidney-Yang deficiency syndrome is the most common type of failure,and TCM disease location syndrome is the most common in kidney.The disease deficiency is mostly Yang deficiency,and the excess is mostly blood stasis.

Objective:To investigate the incidence of mild cognitive impairment(MCI)and malnutrition among centenarians, as well as to explore the relationship between cognitive impairment and nutritional status.Methods:A cross-sectional study was conducted between November and December 2023, involving 121 elderly individuals aged ≥ 100 years in the Baoshan District of Shanghai.The survey collected general information and included the Ascertain Dementia 8-item Questionnaire(AD8), the Mini Nutritional Assessment Short-Form(MNA-SF), and anthropometric nutritional measurements such as waist circumference(WC), hip circumference(HC), arm circumference(AC), calf circumference(CC), and grip strength.The prevalence of MCI and malnutrition among centenarians was calculated, and the correlation between MCI and MNA-SF scores, along with anthropometric nutritional measurement indicators, was analyzed.Results:The age range of centenarians was between 100 and 105 years, with an average age of 101.0±3.5 years.The majority of centenarians were female(76.9%), illiterate(58.7%), and lived with family members(73.6%).All participants had medical insurance(100%).Most had no history of long-term smoking 118(97.5%), long-term alcohol consumption 108(89.3%), long-term use of health supplements 109(90.1%), long-term tea or coffee habits 114(94.2%), chronic medical conditions 84(69.4%), or family history of dementia 102(84.3%).Additionally, 62(51.2%)reported their health status over the past year as general.According to the AD8 screening results, the negative and positive detection rates of MCI in centenarians were 79(65.3%)and 47(34.7%), respectively.Based on the MNA-SF scoring results, the detection rates of normal nutrition, malnutrition risk, and malnutrition among centenarians were 36(29.8%), 61(50.4%), and 24(19.8%), respectively.There was a statistically significant difference in AC between the non-MCI group and the MCI group among centenarians( t=0.01, P=0.03).The AD8 scores of centenarians were significantly negatively correlated with AC, CC, and MNA-SF scores( r=-0.20, r=-0.26, r=-0.29; all P<0.05). Conclusions:The cognitive function of centenarians is associated with their nutritional status, indicating that higher cognitive abilities correlate with better nutritional status.

Objective:To investigate the efficacy of venetoclax combined with hypomethylating agents (Ven-HMA), in patients with core binding factor acute myeloid leukemia (CBF-AML) intolerant to intensive induction therapy.Methods:This study retrospectively analyzed patients newly diagnosed with CBF-AML who were aged <60 years and who received Ven-HMA as induction therapy at the Department of Hematology, the First Affiliated Hospital of Soochow University, between January 2020 and June 2023. Baseline characteristics and treatment responses of the patients were collected.Results:A total of 70 treatment-na?ve patients receiving Ven-HMA induction therapy were enrolled, of which 38 were men and 32 women [median age: 43 (34 - 55) years]. Of the 70 patients, 44 (62.9%) achieved complete remission (CR) /CR with incomplete hematologic recovery (CRi), 16 (22.9%) achieved partial remission, and 10 (14.2%) exhibited no response after one induction cycle. Among the 32 t (8;21) -positive patients with AML, only 8 (25.0%) achieved CR/CRi, of whom 3 (37.5%) remained measurable residual disease (MRD) -positive; among the 38 inv (16) -positive patients, 36 (94.7%) achieved CR/Cri, of whom 12 (33.3%) remained MRD-positive. Patients harboring the CBFβ::MYH11 fusion gene showed significantly higher response rates to Ven-HMA induction than those with the RUNX1:: RUNX1T1 fusion gene ( P<0.01) . Conclusion:Ven-HMA represents a novel therapeutic strategy that exhibits significant efficacy in inv (16) -positive patients; however, it demonstrates relatively lower remission rates in t (8; 21) -positive patients.

Background The neck, shoulders, and lower back are the primary affected areas of work-related musculoskeletal disorders. In manual tasks, combinations of hand functional height (defined as working height below the waist), awkward postures, and cognitive load are common risk factors. However, there is limited literature documenting how these factors specifically alter biomechanical load on the neck, shoulders, and lower back when working at hand functional height. Objective To explore quantitative differences in biomechanical load on the neck, shoulders, and lower back of workers performing manual tasks at hand functional height under different postures and cognitive load combinations. Methods A 3x2 within-subject design was implemented, with three postures (squat, kneeling, and stoop) and two levels of cognitive load (with cognitive load induced by a 2back task and without cognitive load). Ten male university students were recruited to perform a predetermined assembly task (a sequence of loosening and tightening screws) at hand functional height. Surface electromyography (sEMG) and 3D motion capture system were employed to assess the participants’ trunk biomechanical load in executing the tasks. Additionally, subjective perception, including fatigue, muscle pain, and cognitive load, were evaluated using scales. Results Significant variations in biomechanical load were observed across the three postures (P<0.05). The stoop posture exhibited the lowest muscle activation in most target muscles, except for the sternocleidomastoid, and showed the fastest decline in instantaneous median frequency (IMF) of the erector spinae, with a rate of (-0.050±0.008) Hz per unit time (0.128 s), and the greatest trunk flexion angle (35.14°±4.40°). Performing the task by squatting resulted in the highest muscle activation, especially in the upper trapezius, where maximum voluntary contraction percentage reached 20.07%±1.26%. In addition, the squatting posture also resulted in larger joint angles in the sagittal plane for the neck (−7.03°±2.70°), shoulders (60.20°±7.89°), and lower back (34.42°±4.20°). The kneeling posture showed intermediate muscle activation, the slowest IMF decline for the erector spinae in the lower back (−0.005±0.008) Hz per unit time (0.128s), and the joint angles were closest to neutral. The task performance results were also superior in the kneeling posture. Regarding cognitive load, no significant differences were found for most biomechanical indicators, except for subjective cognitive load scores, neck flexion, and shoulder external rotation angles. Conclusion In assembly tasks performed at hand functional height, kneeling results in moderate biomechanical load on the neck, shoulders, and lower back while also improves task performance compared to squatting and forward bending. Additionally, no significant effects of cognitive load under the 2back condition on biomechanical load are observed.

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.