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 explore the clinical efficacy of targeted epidural space block combined with acupotomy in the treatment for lumbar disc herniation(LDH)under the monitor of X-ray image,and to analyze the safety of its operation.Methods:A total of 60 LDH patients who admitted to Department of Pain,Jiangyin Affiliated Hospital of Nanjing University of Chinese Medicine from January 2022 to September 2023 were selected,and they were randomly divided into observation group and control group as random number table,with 30 cases in each group.The observation group adopted targeted epidural space block combined with acupotomy under monitor with X-ray for anterior epidural space,while the control group adopted conventionally epidural block,all of which were treated only once.The Visual Analogue Scale(VAS)scores and Oswestry Disability Index(ODI)scores of two groups before treatment and at the 3rd day,7th day and 30th day after treatment were compared.At the 30th day after treatment,the curative effects of two groups were evaluated according to ODI scores,at the same time,the safe distance between puncture and acupotomy in patients of observation group was analyzed.Results:The effective rates of the treatment of observation group and control group were respectively 96.67%and 70%,and the difference of that between the two groups was statistically significant(x2=7.680,P<0.05).The VAS scores of the two groups at the 3rd day,7th day and 30th day after treatment were lower than those before treatment,and the observation group(2.30±0.87),(1.53±0.86)and(1.47±0.81)were lower than the control group(4.43±0.89),(2.23±0.89)and(4.27±0.82),the difference was statistically significant(t=9.374,3.098,13.306,P<0.05).The ODI scores of the two groups were at the 3rd day,7th day and 30th day after treatment were lower than those before treatment,and the differences of them between two groups were statistically significant(t=7.112,10.690,10.151,P<0.05).In 30 patients of observation group,the gap between the dural sac and the inner edge of facet joint on the affected side was larger than 4.0mm in 25 cases,and all of them can safely conduct puncture with targeting.Conclusion:The targeted epidural space block combined with acupotomy by adopting monitor with X-ray image can effectively improve the symptom of pain,and activities of daily life of LDH patients,which treatment is safe and effective.

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 investigate the preferences of elderly chronic disease patients for"internet+nursing services"and provide references for precisely matching their service needs.Methods A questionnaire on service preferences for elderly chronic disease patients was developed based on a discrete choice experi-ment.Face-to-face questionnaire surveys were conducted with 342 respondents selected by random sampling,and preference outcomes were analyzed using a mixed logit model.Results A total of 342 collected question-naires were valid,resulting in a 100%response rate.Significant differences were observed in all six included attributes(P＜0.05).Senior nurses(β=0.491)provided the highest utility,followed by larger hospital size(β=0.479)and 70%medical insurance reimbursement(β=0.402).Respondents showed the highest willing-ness-to-pay for senior nurses,with 165.1 yuan willingness to pay when switching from junior to senior nur-ses..Conversely,respondents required 86.8 yuan compensation when switching from basic to personalized service packages.Conclusion Preferences for"internet+nursing services"among elderly chronic disease pa-tients are multifactorial,and involving trade-offs among attribute levels during service selection.

Objective To explore the regulatory effect of long non-coding RNA HOX transcript anti-sense RNA(lnRNA HOTAIR)targeting tuberous sclerosis complex 1(TSC1)on podocyte injury in diabetic nephropathy(DN).Methods Mice podocyte MPC5 were divided into 6 groups:the control group,the high glucose group(the HG group),the HG+si-NC group,the HG+si-HOTAIR group,the HG+si-HOTAIR+sh-NC group,and the HG+si-HOTAIR+sh-TSC1 group.qPCR was used to detect the levels of lnRNA HO-TAIR and TSC1 mRNA.Cell viability was detected by cell counting kit-8(CCK-8),and apoptosis was detec-ted by flow cytometry.ELISA was used to detect the levels of inflammatory factors[IL-6,tumor necrosis fac-tor-α(TNF-α)]and the levels of oxidative stress indicators[reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD)]were detected by corresponding reagent kit.Results Compared with the control group,the levels of lnRNA HOTAIR,apoptosis rate,IL-6,TNF-α,ROS and MDA in the HG group were significantly increased(P<0.05),while the levels of TSC1 mRNA,cell viability and SOD were significantly decreased(P<0.05).Compared with the HG+si-NC group,the levels of lnRNA HOTAIR,ap-optosis rate,IL-6,TNF-α,ROS and MDA in the HG+si-HOTAIR group significantly decreased(P<0.05),the levels of TSC1 mRNA,cell viability and SOD were significant increased(P<0.05).Compared with the HG+si-HOTAIR+sh-NC group,the levels of apoptosis rate,IL-6,TNF-α,ROS and MDA in the HG+si-HOTAIR+sh-TSC1 group were significantly increased(P<0.05),the levels of TSC1 mRNA,cell viability and SOD were significantly decreased(P<0.05).Conclusion Silencing lnRNA HOTAIR can target TSC1 to regulate the activity,apoptosis rate,inflammatory level and oxidative stress levels of podocyte injury in DN,thereby alleviating podocyte damage in DN.

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 effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism.[Methods]C57BL/6J mice were randomly divided into saline group(Saline)and hypertension group(Ang Ⅱ,which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps),and supplemented daily with nicotinamide mononucleotide(300 mg/kg),a precursor of NAD+.Blood pressure,endothelial relaxation function and pulse wave velocity were measured after 4 weeks.Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro.mtROS levels were detected by immunofluorescence staining.RT-PCR was used to detect the mRNA expression of mtDNA,SIRT3 and isocitrate dehydrogenase 2(IDH2).8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay.The protein expression levels of p-eNOS,eNOS,SIRT3 and IDH2 were detected by Western blot.[Results]NMN supplementation reduced blood pressure(P<0.001)and improved endothelial function and arterial stiffness(P<0.001)in hypertensive mice.In vitro,NMN improved endothelial function in Ang Ⅱ-stimulated endothelial cells(P<0.05)and attenuated mitochondrial oxidative stress levels(P<0.001).Mechanistically,NMN elevated SIRT3 activity(P<0.001),which subsequently enhanced IDH activity(P<0.001)and reduced oxidative stress levels in endothelial cells.Conversely,knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function(P<0.001).[Conclusion]NAD+lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

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 analyze the predictive value of the prognostic nutritional index combined with inflammatory indicators for clinical outcomes in patients with ischemic stroke, providing a basis for targeted therapeutic interventions and nursing care for patients at potential risk of poor outcomes.Methods:This retrospective cohort study recruited 424 ischemic stroke patients admitted to the Stroke Center of the First Hospital of Jilin University from June 2021 to May 2024 by the convenience sampling method. Collect the general demographic data, routine laboratory examination results within 24 hours of admission, as well as the National Institutes of Health Stroke Scale (NIHSS) scores at admission and discharge of the patients. Based on 3-month functional outcomes, patients were divided into a favorable prognosis group and a poor prognosis group. Univariate analysis, least absolute shrinkage and selection operator regression, and binary Logistic regression were employed to screen predictive variables and develop a nomogram model. Internal validation was performed using the Bootstrap method. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve were drew to evaluate the predictive performance of the model.Results:The favorable prognosis group comprised 256 patients, including 57 females and 199 males, with an age of 61(54, 68) years. The poor prognosis group included 168 patients, with 55 females and 113 males, and an age of 66(58, 72) years. Binary Logistic regression identified age, sex, hyperlipidemia, NIHSS score at discharge, prognostic nutritional index, systemic inflammatory response index, and systemic immune-inflammation index as independent predictors of prognosis in ischemic stroke patients ( χ2 values were 4.52-56.18, all P<0.05). The prediction model demonstrated the area under the curve of ROC of 0.806 (95% CI 0.764-0.849), with an optimal cutoff value of 0.406, achieving specificity of 78% and sensitivity of 68%. The Hosmer-Lemeshow test yielded a non-significant P>0.05, and the calibration curve showed good agreement between predicted and observed outcomes, with a mean absolute error of 0.012. Decision curve analysis confirmed the clinical utility of the model across a wide range of threshold probabilities. Conclusions:The integrated prognostic model combining the prognostic nutritional index and inflammatory indicators demonstrated favorable discriminative ability, robust calibration, and substantial clinical utility. This risk stratification tool shows high applicability for predicting ischemic stroke outcomes, facilitating early identification of high-risk patients with poor prognosis and guiding personalized intervention strategies.

Objective:To analyze the predictive value of the prognostic nutritional index combined with inflammatory indicators for clinical outcomes in patients with ischemic stroke, providing a basis for targeted therapeutic interventions and nursing care for patients at potential risk of poor outcomes.Methods:This retrospective cohort study recruited 424 ischemic stroke patients admitted to the Stroke Center of the First Hospital of Jilin University from June 2021 to May 2024 by the convenience sampling method. Collect the general demographic data, routine laboratory examination results within 24 hours of admission, as well as the National Institutes of Health Stroke Scale (NIHSS) scores at admission and discharge of the patients. Based on 3-month functional outcomes, patients were divided into a favorable prognosis group and a poor prognosis group. Univariate analysis, least absolute shrinkage and selection operator regression, and binary Logistic regression were employed to screen predictive variables and develop a nomogram model. Internal validation was performed using the Bootstrap method. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve were drew to evaluate the predictive performance of the model.Results:The favorable prognosis group comprised 256 patients, including 57 females and 199 males, with an age of 61(54, 68) years. The poor prognosis group included 168 patients, with 55 females and 113 males, and an age of 66(58, 72) years. Binary Logistic regression identified age, sex, hyperlipidemia, NIHSS score at discharge, prognostic nutritional index, systemic inflammatory response index, and systemic immune-inflammation index as independent predictors of prognosis in ischemic stroke patients ( χ2 values were 4.52-56.18, all P<0.05). The prediction model demonstrated the area under the curve of ROC of 0.806 (95% CI 0.764-0.849), with an optimal cutoff value of 0.406, achieving specificity of 78% and sensitivity of 68%. The Hosmer-Lemeshow test yielded a non-significant P>0.05, and the calibration curve showed good agreement between predicted and observed outcomes, with a mean absolute error of 0.012. Decision curve analysis confirmed the clinical utility of the model across a wide range of threshold probabilities. Conclusions:The integrated prognostic model combining the prognostic nutritional index and inflammatory indicators demonstrated favorable discriminative ability, robust calibration, and substantial clinical utility. This risk stratification tool shows high applicability for predicting ischemic stroke outcomes, facilitating early identification of high-risk patients with poor prognosis and guiding personalized intervention strategies.