To improve the targeted therapeutic effect of magnolol (Mag) on neuroblastoma, Mag-loaded mitochondria-targeting immunoliposomes modified by datuximab (aGD2) and triphenylphosphine (TPP) (Mag/aGD2-T-ILN) were prepared, and their physicochemical properties, targeting characteristics and anti-tumor activity were evaluated. Physico-chemical properties showed that the surface of Mag/aGD2-T-ILN was smooth and spherical, with good dispersibility. The particle sizes, PDI and Zeta potentials of Mag/aGD2-T-ILN were measured to be (136.5 ± 5.1) nm, 0.184 ± 0.010 and (27.5 ± 3.6) mV, respectively. Mag/aGD2-T-ILN could release the drug continuously and slowly, and maintain good stability at 4 ℃. Cytotoxicity test exhibited that the IC50 of 2-ME/aGD2-T-ILN was (4.07 ± 0.48) µmol/L, and compared with free Mag, the toxicity of Mag/aGD2-T-ILN to SH-SY5Y cells increased by 6.4 times. Cellular binding and uptake assays suggested that Rho-aGD2-T-ILN could specifically target GD2-positive tumor cells and then further reach their mitochondria. Therapeutic efficacy indicated that Mag/aGD2-T-ILN could better suppress the growth of SH-SY5Y tumor cells in the body with lower toxicity and less side-effects. The results demonstrated that the Mag/aGD2-T-ILN nanoparticles system could achieve intracellular endocytosis through specific binding of antibodies and antigens between the carrier and the surface of tumor cells and electrostatic interaction, then effectively delivered and released the drugs into mitochondria by crossing the mitochondrial phospholipid membrane through TPP, and thus achieving mitochondria-targeting therapy of Mag/aGD2-T-ILN. Through the construction of this active targeting delivery system, the clinical application value of datuximab and Mag is improved, providing a novel approach for the clinical treatment of neuroblastoma.

Objective To clarify the evidence of the frequency and risk factors for falls in knee osteoarthritis(KOA)of adults by meta-analysis.Methods Computerized searches of the CNKI,VIP,Wanfang data,CBM,PubMed,Cochrane Library,Embase,Web of Science were conducted for literature on risk factors for falls in adults with KOA from the inception of the databases to August 2024.After literature screening,data extraction,and quality evaluation,RevMan 5.4 software was used for Meta-analysis.Results A total of 26 articles were involved.Meta-analysis result showed that the rate of falls was 29.0％.Factors associated with increased risk of falls included being female(OR=1.35),decreased lower limb muscle strength(OR=1.72),decreased knee flexion muscle strength(OR=7.05),decreased static posture stability(OR=1.28),opioid use(OR=1.79),antidepressant use(OR=1.69),frequent stair climbing(OR=7.58),combined neurological disease(OR=1.77),history of falls(OR=3.29)and fear of falling(OR=2.54).Conclusion The rate of falls of patients with KOA is high.The adults with KOA who are women,have lower muscle strength of lower limbs and knee flexion muscle strength,poorer static posture stability,use opioids,antidepressant,frequent stair climbing,combined neurological disorders,previous falls in the past year and fear of falls are at higher risk of falls.Healthcare professionals should dynamically assess and detect the risk of falls in the patients with KOA and adopt targeted,individualized interventions to prevent falls.

Objective To construct a prediction model for the progression of knee osteoarthritis(KOA)based on ultrasound score,magnetic resonance imaging(MRI)score,and serum levels of transforming growth factor-β1(TGF-β1)and cathepsin D(Cat D).Methods Clinical data from 270 patients with KOA in Hengshui People's hospital from December 2022 to June 2024 were retrospec-tively analyzed.The patients were randomly divided into a modeling set(n=189)and validation set(n=81)at a ratio of 7∶3.The patients in the modeling set were categorized into mild-to-moderate and severe groups based on the degree of disease progression.Mul-tivariate logistic regression analysis was used to identify factors influencing KOA progression,and a prediction model was constructed using R software.Results Multivariate logistic regression analysis showed that body mass index,knee injury history,ultrasound score,WORMS score,TGF-β1,and Cat D were significant predictors of KOA progression(P＜0.05).A nomogram-based prediction model was developed using these variables.The areas under the curve(AUC)of the nomograms for predicting disease progression in the modeling and validation sets were 0.889 and 0.860,respectively.The calibration curves showed that the predicted probability was in good agreement with the actual probability.Conclusion The prediction model developed in this study is effective in identifying patients at high-risk of KOA progression and may servce as a valuable tool for clinical assessment and decision making.

Objective To construct a prediction model for the progression of knee osteoarthritis(KOA)based on ultrasound score,magnetic resonance imaging(MRI)score,and serum levels of transforming growth factor-β1(TGF-β1)and cathepsin D(Cat D).Methods Clinical data from 270 patients with KOA in Hengshui People's hospital from December 2022 to June 2024 were retrospec-tively analyzed.The patients were randomly divided into a modeling set(n=189)and validation set(n=81)at a ratio of 7∶3.The patients in the modeling set were categorized into mild-to-moderate and severe groups based on the degree of disease progression.Mul-tivariate logistic regression analysis was used to identify factors influencing KOA progression,and a prediction model was constructed using R software.Results Multivariate logistic regression analysis showed that body mass index,knee injury history,ultrasound score,WORMS score,TGF-β1,and Cat D were significant predictors of KOA progression(P＜0.05).A nomogram-based prediction model was developed using these variables.The areas under the curve(AUC)of the nomograms for predicting disease progression in the modeling and validation sets were 0.889 and 0.860,respectively.The calibration curves showed that the predicted probability was in good agreement with the actual probability.Conclusion The prediction model developed in this study is effective in identifying patients at high-risk of KOA progression and may servce as a valuable tool for clinical assessment and decision making.

Objective To clarify the evidence of the frequency and risk factors for falls in knee osteoarthritis(KOA)of adults by meta-analysis.Methods Computerized searches of the CNKI,VIP,Wanfang data,CBM,PubMed,Cochrane Library,Embase,Web of Science were conducted for literature on risk factors for falls in adults with KOA from the inception of the databases to August 2024.After literature screening,data extraction,and quality evaluation,RevMan 5.4 software was used for Meta-analysis.Results A total of 26 articles were involved.Meta-analysis result showed that the rate of falls was 29.0％.Factors associated with increased risk of falls included being female(OR=1.35),decreased lower limb muscle strength(OR=1.72),decreased knee flexion muscle strength(OR=7.05),decreased static posture stability(OR=1.28),opioid use(OR=1.79),antidepressant use(OR=1.69),frequent stair climbing(OR=7.58),combined neurological disease(OR=1.77),history of falls(OR=3.29)and fear of falling(OR=2.54).Conclusion The rate of falls of patients with KOA is high.The adults with KOA who are women,have lower muscle strength of lower limbs and knee flexion muscle strength,poorer static posture stability,use opioids,antidepressant,frequent stair climbing,combined neurological disorders,previous falls in the past year and fear of falls are at higher risk of falls.Healthcare professionals should dynamically assess and detect the risk of falls in the patients with KOA and adopt targeted,individualized interventions to prevent falls.

Objective To explore the value of dynamic ultrasound combined with 3.0T MRI for diagnosing and typing synovial plica of knee joint.Methods Dynamic ultrasound and 3.0T MRI data of 100 patients with suspected synovial plica of knee joint were retrospectively analyzed.Taking the results of arthroscopy as standards,the efficacy of dynamic ultrasound and 3.0T MRI alone and their combination for diagnosing synovial plica of knee joint were evaluated and compared.The length and thickness of synovial plica of knee joint measured with dynamic ultrasound,3.0T MRI alone and their combination were compared with those of arthroscopy,and the consistencies of the location and classification of synovial plica of knee joint with arthroscopy were analyzed.Results Synovial plica was detected in 70 cases,including 11 cases of supropatellar synovial plica,15 cases of infrapatellar synovial plica,medial patellar in 30 cases and lateral patellar synovial plica in 14 cases,among them type A,B,C and D were classified in 9,35,23 and 3 cases,respectively.No significant difference of sensitivity was found between dynamic ultrasound and 3.0T MRI alone for diagnosing synovial plica of knee joint(P＞0.05),which were both lower than that of their combination(both P＜0.05).The length and thickness of knee synovial plica measured with dynamic ultrasound and 3.0T MRI alone were lower than those measured with their combination and arthroscopy(all P＜0.05),and there was no significant difference between the results of their combination and arthroscopy(both P＞0.05).Dynamic ultrasound,3.0T MRI alone and their combination had high consistency of location(Kappa=0.755,0.826,0.897)and classification of knee synovial plica with those of arthroscopy(Kappa=0.721,0.744,0.860).Conclusion Dynamic ultrasound combined with 3.0T MRI was valuable for diagnosing and typing of synovial plica of knee joint.

Objective To observe the clinical efficacy of neck-shoulder-waist-leg pain cataplasms combined with electroacupuncture in the treatment of acute cervical radiculopathy(CR)with qi stagnation and blood stasis syndrome;To evaluate the synergistic effect and safety of neck-shoulder-waist-leg pain cataplasms.Methods Totally 132 CR patients with qi stagnation and blood stasis type in acute stage were randomly divided into treatment group(66 cases)and control group(66 cases).The treatment group was treated with electroacupuncture combined with neck-shoulder-waist-leg pain cataplasms,and the control group was treated with electroacupuncture combined with placebo.Both groups were treated once a day for 5 days and then rested for 2 days for 3 weeks,and follow-up was performed at 1 and 2 weeks after treatment.Clinical efficacy of both groups was observed.The short-form McGill pain questionnaire(SF-MPQ)score,neck disability index(NDI)score,and the F-wave conduction velocity of the median nerve and ulnar nerve were compared before and after treatment and at follow-up.Results 5 and 7 cases were lost in the treatment group and the control group,respectively.The total effective rate of the treatment group was 91.80%(56/61),and the recovery rate was 36.07%(22/61).The total effective rate of the control group was 84.75%(50/59),and the recovery rate was 18.65%(11/59).The difference in recovery rates between the two groups was statistically significant(P<0.05).Compared with before treatment,the SF-MPQ score and NDI score in both groups improved significantly(P<0.05)after treatment and at 1 and 2 weeks of follow-up,and the F-wave conduction velocity of the median and ulnar nerves increased significantly(P<0.05)after treatment.Comparison between two groups at the same time points showed that the SF-MPQ score and NDI score of the treatment group were better than those of the control group(P<0.05)after treatment and at 1 and 2 weeks of follow-up,and the F-wave conduction velocity of the median and ulnar nerves was faster than that of the control group(P<0.05)after treatment.There were no serious adverse reactions in the two groups.Conclusion Neck-shoulder-waist-leg pain cataplasms combined with electroacupuncture can improve the clinical symptoms of CR with qi stagnation and blood stasis syndrome in acute stage.Electroacupuncture plus neck-shoulder-waist-leg pain cataplasms can speed up the recovery process of the disease,which has synergistic effect.

Objective: To systematically evaluate the incidence and influencing factors of depression in family caregivers of Alzheimer's disease (AD) patients, so as to provide the basis for the prevention and treatment of depression among the family caregivers of AD patients. Methods: Publications pertaining to depression in family caregivers of AD patients were retrieved from CNKI, Wanfang Data, PubMed and other databases from the time of their establishment to June 15, 2023. The evaluation criteria recommended by the Agency for Healthcare Research and Quality (AHRQ) and the Newcastle-Ottawa Scale were used to assess the quality of cross-sectional and cohort studies, respectively. Stata 16.0 and Revman 5.4 softwares were used to conduct a meta-analysis on the incidence and influencing factors of depression in family caregivers of AD patients. Sensitivity analysis and publication bias assessment were also performed on the results. Results: A total of 2 324 articles were retrieved, and ultimately 14 articles were included, with a total sample size of 8 313 individuals. There were 6 high-quality articles and 8 moderate-quality articles. Meta-analysis showed that the incidence of depression in family caregivers of AD patients was 37.5% (95%CI: 30.2%-45.1%). Factors associated with depression included patients' high degree of dementia (OR=1.718, 95%CI: 1.059-2.789), patients' low scores on Activities of Daily Living Scale (OR=1.344, 95%CI: 1.059-1.706), patients' psychobehavioral abnormalities (OR=1.248, 95%CI: 1.155-1.348), long duration of caregiving (OR=1.998, 95%CI: 1.637-2.437), less involvement of other family members in caregiving (OR=1.597, 95%CI: 1.237-2.061), low educational level (OR=1.191, 95%CI: 1.044-1.359), poor caregiving skills (OR=3.060, 95%CI: 2.257-4.149), poor self-rated health (OR=2.536, 95%CI: 1.114-5.771) and social support (OR=0.424, 95%CI: 0.232-0.774). The results of depression incidence demonstrated good stability with no significant publication bias. However, publication bias was observed in the influencing factors for depression, which were patients' high degree of dementia and patients' low scores on Activities of Daily Living Scale. Conclusions The incidence of depression in family caregivers of AD patients ranges from 30.2% to 45.1%. It is primarily influenced by the severity of patients' symptoms and ability to perform daily activities, and caregivers' educational level, caregiving skills, health status, caregiving duration and social support.

Objective To develop and test the reliability and validity of the Intrinsic Capacity Assessment Scale for the Older People,so as to provide an effective tool for the assessment of the intrinsic capacity of the aged.Methods Based on the International Classification of Functioning,Disability and Health(ICF)as the theoretical framework,the initial version of The Intrinsic Capacity Assessment Scale for the Older People was developed through literature analysis,Delphi expert consultation and pre-survey.From July to September 2023,650 old people were selected by convenience sampling method to conduct a survey,and 20 old people were surveyed after 2 weeks again to test the reliability and validity of the scale.Results The effective questionnaire recovery rates of the 2 rounds of expert correspondence were 92.3％and 91.7％;the expert authority coefficients were 0.83 and 0.86;the mean importance scores of items were 2.04-3.79 and 3.50-3.82,and the full score ratios were 4.2％-83.3％and 54.6％-86.4％,respectively.The coefficients of variation were 0.11-0.42 and 0.11-0.23,respectively.A total of 5 common factors were extracted from exploratory factor analysis,and the cumulative variance contribution rate was 68.327％.The results of confirmatory factor analysis showed that the fit indexes were x2/df=1.908,RMSEA=0.054,CFI=0.931,IFI=0.932,TLI=0.922,indicating a good fit.The Cronbach's α coefficient of the scale was 0.944;the split half reliability was 0.806;the retest reliability was 0.933.The content validity index of item level was 0.82-1.00,and the content validity index of scale level was 0.91.The Intrinsic Capacity Assessment Scale for the Older People included 35 items in 5 dimensions:movement,vitality,sensation,cognition and psychology.Conclusion The Intrinsic Capacity Assessment Scale for the Older People has good reliability and validity,and it can be used as a reliable tool to evaluate the intrinsic capacity level of the aged.

The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAc^CRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAc^CRH neurons during wakefulness and rewarding stimulation. Activation of NAc^CRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAc^CRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAc^CRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAc^CRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.
Animals ; Septal Nuclei/metabolism* ; Nucleus Accumbens/physiology* ; Corticotropin-Releasing Hormone/metabolism* ; Wakefulness/physiology* ; Neurons/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Neural Pathways/physiology* ; Anxiety/physiopathology* ; Reward