The activation of Keap1-Nrf2 signaling pathway is an important mechanism for cells to resist oxidative stress.Under oxidative stress,Keap1 is affected by post-translational modification(PTM)such as glutathione,alky-lation and S-sulfhydrylation,which weakens its binding to Nrf2,leading to Nrf2 accumulation,nuclear translocation and the expression and transcription of downstream detoxification and antioxidant defense proteins.The PTM of Keap1 is involved in the regulation of a variety of oxidative stress-related diseases such as cancer,Parkin-son's disease and atherosclerosis.For example,alkylation inhibits abdominal aortic aneurysm formation,methylation promotes innate resistance of breast cancer,and S-sulfhydrylation improves atherosclerosis,which pro-vides a theoretical basis for finding new drug targets and biomarkers.

Objective:To evaluate the efficacy and safety of eculizumab in treating acute attacks of aquaporin-4 antibody(AQP4-IgG)positive neuromyelitis optica spectrum disorder(NMOSD).Methods:Six patients with AQP4-IgG-positive NMOSD treated with eculizumab at the Affiliated Hospital of Qingdao University from August 2023 to April 2024 were included.The patients' clinical characteristics, changes in scores of neurological function, pain and spasm before and after eculizumab treatment, and adverse drug reactions during the treatment period were described, and the data were subjected to Friedman test using SPSS 25.0.Results:The median score of expanded disability status scale in the six patients decreased from 3.25 before treatment to 1.25 after treatment, and the difference was statistically significant ( F=44.77, P<0.01).The functional status score showed noticeable improvement as early as week 1, demonstrating greater sensitivity to treatment response.Three patients experienced moderate to severe pain before treatment, with a mean pain score of 6, which reduced to 4.67 and 1.33 at week 2 and 6, respectively( F=29.17, P<0.05).Two patients reported spasms before treatment, with a mean score of 3.00, which decreased to 2.00, 1.50, and 1.00 at week 2, 3, and 6 after treatment, respectively( F=18.00, P>0.05).No serious adverse reactions were reported during the treatment. Conclusion:Eculizumab can effectively improve the neurological function and alleviate pain in patients with AQP4-IgG-positive NMOSD during acute attacks, and demonstrate good safety.

Objective To explore the value of ultrasound deep learning(DL)model for diagnosis and classification of cystocele.Methods Totally 696 female patients who underwent pelvic floor ultrasound were retrospectively collected and divided into model development dataset(n=576)and test set(n=120).The former included 432 cases of cystocele and 144 cases of non-cystocele,while the latter included 90 cases of cystocele and 30 cases of non-cystocele.Patients in model development dataset were randomly divided into training set(n=460,including 345 cases of cystocele and 115 cases of non-cystocele)and validation set(n=116,including 87 cases of cystocele and 29 cases of non-cystocele)at the ratio of 8∶2.DL model was trained and established using Vision Transformer architecture based on pelvic floor ultrasound data in training and validation sets for diagnosis and classification of cystocele(non-or Green Ⅰ,Ⅱ and Ⅲ type).Taken diagnostic results of senior ultrasound physicians as standard,the diagnostic efficacy of DL model was evaluated,and its diagnostic efficacy and efficiency were compared with those of 2 junior ultrasound physicians.Results The macro average precision,F1 score,area under the curve(AUC)and overall accuracy of DL model for diagnosis and classification of cystocele in validation set was 90.84％,89.28％,0.97 and 89.66％,respectively,while in test set was 80.85％,79.92％,0.92 and 80.00％,respectively.The overall diagnostic accuracy of 2 junior ultrasound physicians for diagnosis and classification of cystocele in test set was 70.00％(84/120)and 68.33％(82/120),respectively,both lower than that of DL model(P=0.023,0.011).The diagnostic time of DL model was 0.098 s for each case,of junior ultrasound physicians was 46(36,56)s for each case,the former had better diagnostic efficacy(P＜0.001).Conclusion Ultrasound DL model could be used for diagnosis and classification of cystocele.

Cancer cachexia is a complex syndrome caused by multiple factors,which seriously affects the quality of life and prognosis of patients.Its overall pathogenesis is related to the deficiency of spleen qi,insufficiency of kidney essence,internal generation of turbid toxins,and the obstruction of the production of qi,blood and essential qi,which cannot nourish the muscles and bones.Under the guidance of the dynamic diagnosis and treatment system of"spleen and kidney exhaustion as the root cause and internal accumulation of turbid toxins as the manifestation",the overall regulation is carried out from four dimensions:opening and closing the spleen and stomach,nourishing the kidney and promoting transportation,transforming turbid toxins and detoxification,and tonifying qi and nourishing yin.It has shown unique value in the intervention of cancer cachexia and can provide ideas and references for the clinical practice of TCM in treating cancer cachexia.

Objective:To investigate the multimorbidity of myopia and obesity, as well as myopia and malnutrition, among children and adolescents aged 7-18 in Guangdong Province and analyze their epidemiological characteristics and related factors.Methods:A stratified random cluster sampling method was used to select 274 939 children and adolescents aged 7-18 from 21 cities in Guangdong Province in 2023. Physical examination information such as height, weight, distance vision, and diopter, as well as questionnaire survey information on dietary behavior, physical activity, screen behavior, sleep time, etc., were collected to analyze the current status and trends of multimorbidity between myopia and obesity, myopia and malnutrition. The multivariate logistic regression model was used to analyze the related factors of multimorbidity.Results:The multimorbidity rates of myopia and obesity, myopia and malnutrition in children and adolescents aged 7-18 in Guangdong Province in 2023 were 4.43% and 6.40%, respectively. The multimorbidity rates for males were 5.44% and 6.88%, respectively, which were higher than those for females, about 3.31% and 5.88% (both P<0.001). The multimorbidity rates of urban students were 5.03% and 6.73%, respectively, which were higher than those of county students at 4.03% and 6.18% (both P<0.001). The multimorbidity rates of myopia and obesity, myopia and malnutrition increased with the increase of academic stage (all P<0.001). The multimorbidity rates of myopia and obesity, as well as myopia and malnutrition, fluctuated with age, with the first decrease occurring at the age of 12. The multivariate logistic regression analysis showed that compared to children and adolescents aged 7-18 who had daily after-school tutoring <2 hours, daily screen time <2 hours, did not consume sugary drinks every day, sleep time that could meet health requirements daily, and exercised≥60 minutes of moderate-to vigorous-physical activity ≥60 minutes for at least 3 days per week, those who had daily after-school tutoring ≥2 hours ( OR=1.18, 95% CI: 1.11-1.26), daily screen time ≥2 hours ( OR=1.09, 95% CI: 1.02-1.16), consumed sugary drinks every day ( OR=1.20, 95% CI: 1.11-1.30), daily sleep time that could not meet the health requirements ( OR=1.16, 95% CI: 1.09-1.23), and no exercise per week ( OR=1.09, 95% CI: 1.01-1.18) had a higher risk of multimorbidity of myopia and obesity. Compared to children and adolescents who exercised≥60 minutes of moderate-to vigorous-physical activity ≥60 minutes for at least 3 days per week, those who exercised <3 days per week ( OR=1.20, 95% CI: 1.17-1.34) had a higher risk of multimorbidity of myopia and malnutrition. Conclusion:The multimorbidity rates of myopia and obesity, as well as myopia and malnutrition, in children and adolescents aged 7-18 in Guangdong Province are relatively low and fluctuate with age. Physical activity, screen time, consumption of sugary drinks, and sleep time may be associated with these multimorbidities.

New quality productivity is a strategic engine for promoting high-quality development and is an inherent requirement and important focus for enhancing new driving forces and building national advantages.The cultivation of innovative talents and technological innovation are key to the development of new quality productivity.Laboratory animal science is a comprehensive interdisciplinary subject that integrates multiple disciplines including biology,medicine,pharmacy,and biomedical engineering.Teaching and research of laboratory animal science not only promotes the creation of innovative talent teams by cultivating innovative consciousness,thinking,spirit,and operational abilities,but also promotes the development of cutting-edge technologies and the transformation of disruptive research result in the fields of basic research and clinical translation of biomedicine,thus providing important guarantees for China's scientific and technological progress and innovative development.

Objective To investigate the effect of lifestyle on cognitive decline in rural people aged 40 years and older in Xi'an.Methods This was a prospective cohort study.People aged 40 years and older in two villages in Huyi District were selected as the study population.They completed the baseline survey from October 2014 to March 2015 as well as two follow-up visits in 2016 and 2018,respectively.A comprehensive score of lifestyle was calculated based on factors including smoking,drinking,exercise,and diet collected at the baseline.The Mini-Mental State Examination(MMSE)was used to evaluate global cognitive function at both baseline and follow-up;a≥4-point decrease in MMSE score from the baseline was defined as marked cognitive decline.Multivariable Logistic regression,propensity score correction,and propensity score matching were used to investigate the relationship between lifestyle and cognitive decline.Results A total of 1 348 participants were ultimately enrolled and 56(4.2％)of them met the criteria for marked cognitive decline(△MMSE≥4-points).Among them,386(28.6％)people had smoking history,184(13.6％)were drinkers,214(15.9％)lacked physical activity,and 400(29.7％)ate a diet high in oil and salt.Generally,304(22.6％)met the definition of the unhealthy lifestyle(comprehensive score＜6),which means more than one of the four subscales was unhealthy or more than two were relatively unhealthy.Multivariable Logistic regression analysis showed that unhealthy lifestyle was positively associated with marked cognitive decline(OR=2.838,95％CI:1.302-5.525,P=0.005).Propensity-score adjusted model yielded very similar results(OR=2.786,95％CI:1.371-5.661,P=0.005).Propensity score matching was performed to further balance the differences in covariates between the two groups.Multivariate Logistic regression analysis conducted in the matched population revealed that the risk of marked cognitive decline was still higher in those with unhealthy lifestyle(OR=3.994,95％CI:1.582-12.176,P=0.006).Conclusion Unhealthy lifestyle is associated with an increased risk of cognitive decline in cognitively normal people aged 40 years and older.

Objective: To explore the current status of hyperopic reserve and its related factors among non-myopia preschool and primary school students aged 5 to 12 years in Guangdong Province, so as to provide a basis for formulating intervention strategies for the pre myopia stage of children. Methods: From October to December 2023, by using stratified cluster random sampling method, a survey on hyperopic reserve among preschool children and primary school students in Guangdong were conducted. And a total of 10 567 children from the senior class of kindergarten to the sixth grade of primary school who completed autorefraction measurements with and without cycloplegia and the questionnaire survey were included in the study. The prevalence characteristics of low hyperopic reserve among non-myopia children were analyzed, and multivariable Logistic regression was used to analyze the related factors. Results: The prevalence rate of low hyperopic reserve among 8 790 non-myopia children was 62.4%. The average spherical equivalent (SE) for children aged 5 to 12 years was 0.88 (0.25, 1.25)D, decreasing from 1.13 ( 0.75 , 1.50)D in senior kindergarten to -1.00 (-2.50, 0.38)D in sixth grade, with the difference was statistically significant ( H=2 475.3, P <0.01). Multivariable Logistic regression analysis, after adjusting for confounders including gender, urban and rural, and grade, revealed that parental myopia was a risk factor for low hyperopic reserve in the preschool stage (one parent with myopia: OR=1.62, 95%CI =1.35-1.93; both parents with myopia: OR=2.05, 95%CI = 1.66 -2.55); in the lower primary school stage, parental myopia (one parent with myopia: OR=1.46, 95%CI =1.27-1.68; both parents with myopia: OR=1.58, 95%CI =1.33-1.89), frequently or always reading or using electronic screens while lying down or on one s stomach ( OR=1.43, 95%CI =1.13-1.81), and never or occasionally maintaining a viewing distance of over 3 meters when watching TV/playing video games ( OR=1.34, 95%CI =1.04-1.72) were risk factors; in the higher primary school stage, failing to take a break every hour during near work ( OR=1.79, 95%CI =1.16-2.75) was a risk factor (all P <0.05). Conclusions The emmetropization of children aged 5-12 years in Guangdong Province is accelerated, and non-myopia children generally exhibit insufficient hyperopic reserve. The contributing factors for insufficient hyperopia reserve in non-myopia children vary across different educational stages, necessitating targeted precision interventions.

Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*