Kirsten rat sarcoma virus (KRAS) is a common oncogene in human cancers. Approximately 40% of the patients diagnosed with colorectal cancer (CRC) have KRAS mutations that exhibit strong resistance to targeted molecular therapy and EGFR antibody treatment. In this study, we present photocatalytic silica nanoparticles (A6-FS/BiVO₄ DMSNs) for targeted therapy of KRAS mutant CRC with the induction of cascadic ferroptosis events. Dendritic mesoporous silica nanoparticles (DMSNs) were impregnated with photocatalytic BiVO₄, loaded with ferroptotic agents (benzoyl ferrocene: B and sorafenib: S), and encoded with CD44-targeting A6 peptides. For the targeting design, we observed CD44 overexpression in KRAS mutant CRC cells using CPTAC data analysis. Upon laser irradiation, A6-FS/BiVO₄ DMSNs generate electron-hole pairs (e^-/h⁺), which produce hydroxyl radical (OH^·) and superoxide anions (O₂ ^{· -}). Laser irradiation simultaneously initiates the dissociation of iron (Fe²⁺) from benzoyl ferrocene and the release of sorafenib. This cascade induces ferroptosis in KRAS mutant CRC cells, especially under conditional inhibition of redox-regulating proteins (cystine/glutamate antiporter and glutathione peroxidase 4), and significantly inhibits tumor growth in a KRAS mutant CRC xenograft animal model.

Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging. However, investigations into the microstructural pathology of brain white matter (WM) associated with these deficits remain limited. This study aimed to examine the microstructural characteristics of WM in the non-demented population with abnormal color discrimination, utilizing Neurite Orientation Dispersion and Density Imaging (NODDI), and to explore their correlations with cognitive functions and cognition-related plasma biomarkers. The tract-based spatial statistic analysis revealed significant differences in specific brain regions between the abnormal color discrimination group and the healthy controls, characterized by increased isotropic volume fraction and decreased neurite density index and orientation dispersion index. Further analysis of region-of-interest parameters revealed that the isotropic volume fraction in the bilateral anterior thalamic radiation, superior longitudinal fasciculus, cingulum, and forceps minor was significantly correlated with poorer performance on neuropsychological assessments and to varying degrees various cognition-related plasma biomarkers. These findings provide neuroimaging evidence that WM microstructural abnormalities in non-demented individuals with abnormal color discrimination are associated with cognitive dysfunction, potentially serving as early markers for cognitive decline.
Humans ; White Matter/pathology* ; Male ; Female ; Cognitive Dysfunction/physiopathology* ; Middle Aged ; Aged ; Color Perception/physiology* ; Brain/pathology* ; Neuropsychological Tests ; Diffusion Tensor Imaging

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
Dimethyl Fumarate/pharmacology* ; Mitophagy/drug effects* ; Animals ; Mice ; Macrophages/metabolism* ; Periodontitis/prevention & control* ; RAW 264.7 Cells ; Oxidative Stress/drug effects* ; Peptide Elongation Factor Tu/metabolism* ; Mice, Inbred C57BL ; Male ; Mitochondria/drug effects*

ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

Objective To explore the influencing factors of liver fibrosis in patients with metabolic dysfunction-associated fatty liver disease(MAFLD)complicated with chronic hepatitis B(CHB),and to find clinically convenient predictive parameters for assessing liver fibrosis risk.Methods A retrospective analysis was conducted on 221 cases of MAFLD with CHB diagnosed and treated at the Second Hospital of Lanzhou University between January 2015 and August 2022.Patients were divided into low-risk(FIB-4<1.30,n=84),medium-risk(1.30≤FIB-4≤2.67,n=94)and high-risk(FIB-4>2.67,n=43)liver fibrosis groups based on the Fibrosis-4(FIB-4)index.General clinical data,laboratory indicators and composite indicators were compared among the three groups.Variables were screened using forward stepwise regression,and binary logistic regression analysis was performed to determine independent predictors of liver fibrosis.A prediction model was constructed and evaluated using receiver operating characteristic(ROC)curve analysis.Results Age,AST and Triglyceride-glucose index(TyG)were independent risk factors for liver fibrosis in patients with MAFLD combined with CHB,while platelet-to-lymphocyte ratio(PLR)was an independent protective factor(all P<0.05).ROC curve analysis showed that the area under the curve(AUC)for age,AST,TyG,PLR,age-AST and AST-TyG in predicting liver fibrosis were 0.668,0.764,0.680,0.738,0.856 and 0.805,respectively.At the optimal cut-off values,the sensitivities were 86.0%,67.4%,93.0%,62.8%,86.0%and 79.1%,and the specificities were 43.3%,82.0%,51.7%,86.0%,71.3%and 70.2%.Conclusion Age,AST,TyG and PLR are influencing factors of liver fibrosis in MAFLD combined with CHB patients.The parameters established based on these factors may predict the risk of liver fibrosis,and combined prediction can improve predictive efficacy.

Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7％.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P＜0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95％CI:0.566-0.838],social support(aOR=0.979,95％CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95％CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P＜0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P＜0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.

Objective:To analyze the impact of diagnosis-intervention packet payment (DIP) reform on hospitalization service capacity and patients′ economic burden, for references for promoting China′s medical insurance payment reform.Methods:Data were collected from the discharge summarizes of 116 545 hospitalized patients from a tertiary hospital in Guangdong Province. Among them, there were 42 534 cases before the DIP reform (January 2016 to December 2017) and 74 011 cases after the reform (January 2018 to December 2020). The all-cause in-hospital mortality rate, length of hospital stay, disease severity, readmission rate within 30 days, total hospitalization costs, and patient out of pocket expenses were used as evaluation indicators for hospitalization service capacity and patient economic burden. Intermittent time series analysis was conducted to examine the changes in indicators before and after DIP reform.Results:The slope of the change trend of all-cause in-hospital mortality rate and readmission rate within 30 days before and after DIP reform was not statistically significant ( P<0.05); The length of hospital stay showed a decreasing trend before the reform ( P=0.047), but the trend after the reform was not statistically significant ( P=0.776); The change trend of disease severity before the reform was not statistically significant ( P=0.682), but showed a significant upward trend after the reform ( P=0.012); The total hospitalization costs significantly increased during the reform ( P<0.001), but the trend of change after the reform was not statistically significant ( P=0.431); The patient′s out of pocket expenses showed an upward trend before the reform ( P=0.001), but the change trend after the reform was not statistically significant ( P=0.757). Conclusions:DIP reform could help hospitals improve their inpatient service capabilities and enhance their functional positioning; Strengthen medical cost management and control the increase in economic burden on hospitalized patients.

Objective:To investigate the impact of sliding distance of the fmoral neck system (FNS) on the curative efficacy of displaced femoral neck fractures.Methods:A retrospective study was conducted to analyze the clinical data of the 179 patients with displaced femoral neck fracture who had been treated by FNS fixation at Department of Orthopaedics, The Second General Hospital of Fuzhou between September 2019 and September 2023. Based on the FNS sliding distance measured on X-ray films on the day after surgery or one day after surgery, the patients were assigned into 2 groups: a short sliding distance group [sliding distance ≤5 mm, n=55; 35 males, 20 females; median age: 50.0 (34.0, 59.0) years; body mass index (BMI): (24.0±2.4) kg/m 2] and a long sliding distance group [5 mm 0.05). At postoperative 3, 6, and 12 months, the distances of femoral neck shortening in the short sliding distance group [2.5 (0.7, 3.5) mm, 2.6 (0.7, 3.5) mm, and 2.7 (0.7, 3.5) mm] were significantly shorter than those in the long sliding distance group [3.2 (1.3, 5.7) mm, 3.2 (1.3, 7.1) mm, and 3.2 (1.4, 7.1) mm] ( P<0.05). The incidence of moderate-to-severe shortening at one year after surgery in the long sliding distance group [26.6% (33/124)] was significantly higher than that in the short sliding distance group [3.6%(2/55)] ( P<0.05). No significant differences were found between the 2 groups in tip-apex distance, operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, or incidence of complications ( P>0.05). At the last follow-up, the Harris Hip Score in the short sliding distance group [93.5 (88.7, 96.2) points] was significantly higher than that in the long sliding distance group [90.1 (82.9, 94.9) points] ( P<0.05). Conclusion:In the treatment of displaced femoral neck fractures with FSN fixation, compared with those with a long sliding distance, the patients with a short sliding distance demonstrate superior outcomes in postoperative femoral neck shortening and functional recovery of the hip, but no significant difference in the incidence of complications.

Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7％.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P＜0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95％CI:0.566-0.838],social support(aOR=0.979,95％CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95％CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P＜0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P＜0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.

Objective:To analyze the impact of diagnosis-intervention packet payment (DIP) reform on hospitalization service capacity and patients′ economic burden, for references for promoting China′s medical insurance payment reform.Methods:Data were collected from the discharge summarizes of 116 545 hospitalized patients from a tertiary hospital in Guangdong Province. Among them, there were 42 534 cases before the DIP reform (January 2016 to December 2017) and 74 011 cases after the reform (January 2018 to December 2020). The all-cause in-hospital mortality rate, length of hospital stay, disease severity, readmission rate within 30 days, total hospitalization costs, and patient out of pocket expenses were used as evaluation indicators for hospitalization service capacity and patient economic burden. Intermittent time series analysis was conducted to examine the changes in indicators before and after DIP reform.Results:The slope of the change trend of all-cause in-hospital mortality rate and readmission rate within 30 days before and after DIP reform was not statistically significant ( P<0.05); The length of hospital stay showed a decreasing trend before the reform ( P=0.047), but the trend after the reform was not statistically significant ( P=0.776); The change trend of disease severity before the reform was not statistically significant ( P=0.682), but showed a significant upward trend after the reform ( P=0.012); The total hospitalization costs significantly increased during the reform ( P<0.001), but the trend of change after the reform was not statistically significant ( P=0.431); The patient′s out of pocket expenses showed an upward trend before the reform ( P=0.001), but the change trend after the reform was not statistically significant ( P=0.757). Conclusions:DIP reform could help hospitals improve their inpatient service capabilities and enhance their functional positioning; Strengthen medical cost management and control the increase in economic burden on hospitalized patients.