Homeostasis and energy and substance metabolism reprogramming shape various tumor microenvironment to sustain cancer stemness, self-plasticity and treatment resistance. Aiming at them, a lipid-based pharmaceutical loaded with CaO₂ and glucose oxidase (GOx) (LipoCaO₂/GOx, LCG) has been obtained to disrupt calcium homeostasis and interfere with glycometabolism. The loaded GOx can decompose glucose into H₂O₂ and gluconic acid, thus competing with anaerobic glycolysis to hamper lactic acid (LA) secretion. The obtained gluconic acid further deprives CaO₂ to produce H₂O₂ and release Ca²⁺, disrupting Ca²⁺ homeostasis, which synergizes with GOx-mediated glycometabolism interference to deplete glutathione (GSH) and yield reactive oxygen species (ROS). Systematical experiments reveal that these sequential multifaceted events unlocked by Ca²⁺ homeostasis disruption and glycometabolism interference, ROS production and LA inhibition, successfully enhance cancer immunogenic deaths of breast cancer cells, hamper regulatory T cells (Tregs) infiltration and promote CD8⁺ T recruitment, which receives a considerably-inhibited outcome against breast cancer progression. Collectively, this calcium homeostasis disruption glycometabolism interference strategy effectively combines ion interference therapy with starvation therapy to eventually evoke an effective anti-tumor immune environment, which represents in the field of biomedical research.

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.

Objective To explore the value of transvaginal ultrasound five-view method for diagnosing fetal congenital heart disease(CHD)in early pregnancy of high-risk pregnancy.Methods Totally 428 singleton fetuses at 11-13+6 weeks of gestation in high-risk pregnancies were prospectively enrolled.Fetal cardiac examinations were performed using two-dimensional grey scale imaging combined with CDFI via transabdominal ultrasound method,transvaginal ultrasound five-view method(upper abdominal transverse view,four-chamber view,three-vessel and trachea[3VT]view,ventricular outflow tract view and bilateral subclavian artery view)and transvaginal ultrasound two-view method(four-chamber view and 3VT view).Taken results of pregnant metaphase or late pregnancy fetal echocardiography,post-abortion pathology or postnatal neonatal echocardiography as gold standards,the diagnostic performances of the above 3 methods for diagnosing fetal CHD in early pregnancy were compared.Results CHD was diagnosed in 120(120/428,28.04％)fetuses.Transvaginal ultrasound five-view method made 11 false positives and 19 false negatives,with sensitivity,specificity,positive predictive value and negative predictive values for diagnosing fetal CHD in the first trimester of high-risk pregnancy of 84.17％,96.43％,90.18％and 93.99％,respectively,which were all significantly higher than of transvaginal ultrasound two-view method(70.83％,91.88％,77.27％and 88.99％)and transabdominal ultrasound method(72.50％,91.23％,76.32％and 89.49％;all P＜0.05).Conclusion Transvaginal ultrasound five-view method could be used to effectively diagnose fetal CHD in the first trimester of high-risk pregnancy.

[Purpose]To investigate the acceptance and willingness-to-pay(WTP)of combined can-cer screening among rural residents in Shandong Province,and to analyze its influencing factors.[Methods]A face-to-face questionnaire survey was conducted among rural residents aged 40～70 in villages setected by cluster sampling from three counties(county level city or district)in Shan-dong Province.The questionnaire was developed using the method of double-bound dichotomous choice combined with open-ended questions in contingent valuation.The factors influencing inten-sity of WTP was analyzed with using single-factor and ordinary least squares regression models.[Results]A total of 962 subjects were surveyed.89.19％of the respondents were willing to accept cancer combined screening,and 62.00％were willing to pay part of the costs.The average of WTP was 963.67 CNY,which accounted for 32.12％of the total cost.The proportion of respon-dents who were willing to pay between 0～1 500 CNY was the highest(76.49％).In the multivariate analysis,age,sex and income had significant effects on the maximum payment of multi-cancer screening.[Conclusion]The acceptance of multi-cancer screening among rural residents in the study sites is high,but the willingness-to-pay is limited.The out-of-pocket payment for multi-can-cer screening should be controlled,and a co-payment mechanism among government,enterprises,social organizations and individuals should be explored.

Objective:To assess the effects of various leisure hobbies on the ability of daily living(ADL)and the quality of life among older adults in China.Methods:A cross-sectional study was conducted using data from the 4th Chinese Urban and Rural Elderly Living Conditions Sample Survey.We categorized community recreation hobbies into two types: dynamic hobbies, which include walking, playing ball games, dancing, and other physical activities, and static hobbies, which encompass activities that do not require physical exertion, such as reading, watching TV, and drawing.The EuroQol five-dimension scale(EQ-5D)-3L was employed to evaluate the quality of life.Older adults who maintained either dynamic or static hobbies for three consecutive years from 2017 to 2019 were initially screened.The relationship between different types of leisure hobbies and ADL scores, as well as quality of life at various time points, was analyzed using repeated-measures ANOVA.Subsequently, propensity scores were matched based on gender, age, ethnicity, marital status, literacy, and chronic diseases, and five machine learning algorithms were utilized to identify the optimal model for predicting fully independent ADL and EQ-5D effect values.Based on the optimal predictive model, we conducted Shapley Additive Explanations(SHAP)and global analysis.Results:The total number of older adults who participated in the survey over the three consecutive years from 2017 to 2019 was 4 912.Among these, 2 594 individuals maintained the same hobby habits throughout this period, comprising 1 362 males and 1 232 females, with an average age of(70.81±6.71)years.Statistically significant differences in ADL scores and EQ-5D scores were observed between the dynamic and static leisure hobby groups(all P<0.05)across various time points, hobby group classifications, and interaction levels.Older adults engaged in dynamic hobbies exhibited superior ADL functioning and higher EQ-5D scores in comparison to those in the static hobby group, with these differences remaining statistically significant following propensity score matching(all P<0.05).In predicting full ADL independence, the SHAP value for dynamic hobbies ranked second, while for predicting an EQ-5D weighted value of 1, the SHAP value for dynamic hobbies ranked ninth.Overall, the type of dynamic hobby demonstrated a positive trend in its effect on the ability to perform daily activities independently and in achieving an EQ-5D weighted value of 1. Conclusions:In comparison to static hobbies, Chinese older adults who engage in dynamic hobbies exhibit improved daily mobility and a higher quality of life.Furthermore, dynamic hobbies positively influence the capacity for full independence in daily activities, as evidenced by an EQ-5D weighted value of 1.

[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and a leading cause of vision loss globally.Although anti-vascular endothelial growth factor(anti-VEGF)therapies remain the clinical mainstay, a significant proportion of patients exhibit suboptimal responses, highlighting the urgent need for novel therapeutic targets. Calcitonin gene-related peptide(CGRP), a multifunctional neuropeptide, is gaining attention due to its roles in vascular regulation, neuroprotection, and immunomodulation. This review summarizes the biological characteristics of CGRP and its receptor-mediated signaling, and explores emerging evidence of CGRP's involvement in DR through its vasodilatory effects and regulatory effect on neurodegenerative disorders and release of inflammatory cytokines. Furthermore, the therapeutic potential of targeting the CGRP pathway in DR is evaluated, especially in cases unresponsive to VEGF inhibition. Despite currently the lack of CGRP-targeted drugs applied for DR, the peptide demonstrates efficacy and safety in other diseases, such as migraine, suggests promising translational opportunities. However, CGRP may play a dual role in different pathological stages of DR, thus its treatment strategy needs to be considered precisely. Future research elucidating the precise mechanisms of CGRP in DR may pave the way for innovative intervention strategies.

Objective Low-dose CT(LDCT)images significantly affect clinical diagnosis due to the substantial presence of noise and artifacts.To address the challenges such as over-smoothing of images,loss of texture details,and the presence of residual noise artifacts,a deconvolution-convolution residual network integrating multi-scale dilated convolution(MDC-DCRN)is proposed for LDCT denoising.Methods The network employed deconvolution-convolution architecture to better preserve image details and integrated an MDC module to enhance the feature extraction capabilities at different scales.Moreover,the issue of excessive image smoothing was effectively mitigated by the composite loss function combining L1 loss and perceptual loss.Results The experimental results on the Mayo dataset demonstrated that MDC-DCRN outperformed 4 classic denoising methods,namely RED-CNN,EDCNN,WGAN-RAM,and CTformer.MDC-DCRN effectively eliminated noise and artifacts while recovering more texture detail information.Compared with LDCT images,the images processed by MDC-DCRN had an average increase of 13.64%in peak signal-to-noise ratio,an average increase of 4.57%in structural similarity index,and an average decrease of 37.40%in root mean square error.Conclusion The proposed MDC-DCRN model can effectively preserve details while reducing noise from low-dose scanning,offering a novel approach to clinical LDCT image denoising.

Objective To investigate the relationship between calcium-sensing receptor(CaSR)gene rs17251221,rs60388563 loci polymorphisms and the genetic susceptibility of breast cancer(BC).Methods A total of 122 patients with breast cancer admitted to Hengshui Second People's Hospital from January 2022 to June 2024 were selected as the BC group,and 100 healthy women without blood relationship at the same time were selected as the control group.The polymorphisms of CaSR gene rs17251221,rs60388563 loci were detected by polymerase chain reaction(PCR).The clinical data,genotype distribution and allele frequency were compared between the two groups.Non-conditional Logistic regression model was used to analyze the correlation between CaSR gene polymorphism and genetic susceptibility of BC patients.Results Comparing the general data of the two group,the proportion of family history of cancer in the BC group was significantly higher than that in the control group,and the difference was statistically significant(t=12.246,P<0.05).The genotype distribution of CaSR gene rs17251221 and rs60388563 loci in the control group and the BC group was consistent with the Hardy-Weinberg equilibrium law(χ2=0.087～1.202,P＞0.05),which was representative of the population.Under the co-dominant model of rs17251221 and rs60388563 loci,the risk of BC in GG genotype was significantly increased(OR=1.493,95%CI=1.070～2.108;OR=1.483,95%CI=1.034～2.121).Under the dominant model(AA vs GA+GG)and recessive model(GG vs GA+AA),the rs17251221 locus carrying G allele(OR=1.371,95%CI=1.023～1.824)and A allele(OR=0.524,95%CI=0.221～0.926)was significantly associated with the risk of BC(P<0.05).Under the dominant model(CC vs GC+GG)and recessive model(GG vs GC+CC),the rs60388563 locus carrying G allele(OR=1.245,95%CI=1.107～1.461)and C allele(OR=0.682,95%CI=0.523～0.974)was significantly associated with the risk of BC(P<0.05).Conclusion The rs17251221,rs60388563 loci polymorphisms of CaSR gene are closely related to BC susceptibility,and the risk of BC is high in individuals carrying G allele.

Objective To investigate the relationship between calcium-sensing receptor(CaSR)gene rs17251221,rs60388563 loci polymorphisms and the genetic susceptibility of breast cancer(BC).Methods A total of 122 patients with breast cancer admitted to Hengshui Second People's Hospital from January 2022 to June 2024 were selected as the BC group,and 100 healthy women without blood relationship at the same time were selected as the control group.The polymorphisms of CaSR gene rs17251221,rs60388563 loci were detected by polymerase chain reaction(PCR).The clinical data,genotype distribution and allele frequency were compared between the two groups.Non-conditional Logistic regression model was used to analyze the correlation between CaSR gene polymorphism and genetic susceptibility of BC patients.Results Comparing the general data of the two group,the proportion of family history of cancer in the BC group was significantly higher than that in the control group,and the difference was statistically significant(t=12.246,P<0.05).The genotype distribution of CaSR gene rs17251221 and rs60388563 loci in the control group and the BC group was consistent with the Hardy-Weinberg equilibrium law(χ2=0.087～1.202,P＞0.05),which was representative of the population.Under the co-dominant model of rs17251221 and rs60388563 loci,the risk of BC in GG genotype was significantly increased(OR=1.493,95%CI=1.070～2.108;OR=1.483,95%CI=1.034～2.121).Under the dominant model(AA vs GA+GG)and recessive model(GG vs GA+AA),the rs17251221 locus carrying G allele(OR=1.371,95%CI=1.023～1.824)and A allele(OR=0.524,95%CI=0.221～0.926)was significantly associated with the risk of BC(P<0.05).Under the dominant model(CC vs GC+GG)and recessive model(GG vs GC+CC),the rs60388563 locus carrying G allele(OR=1.245,95%CI=1.107～1.461)and C allele(OR=0.682,95%CI=0.523～0.974)was significantly associated with the risk of BC(P<0.05).Conclusion The rs17251221,rs60388563 loci polymorphisms of CaSR gene are closely related to BC susceptibility,and the risk of BC is high in individuals carrying G allele.