BACKGROUND:Precision therapy based on multifunctional nanomaterials is a novel therapeutic model for malignancies that can integrate multiple imaging and therapeutic models into one nanoscale platform to achieve visual combination treatment. OBJECTIVE:To prepare novel nanoparticles loaded with Cu2(OH)PO4 nanoparticles(CuNPs)and nuciferine(NF)(h-PCuNF),and to explore their ability to mediate combined photothermal therapy/photodynamic therapy/chemodynamic therapy/chemotherapy for malignancy. METHODS:The h-PCuNF nanoparticles were synthesized through a double-emulsion procedure,through which the CuNPs and NF were loaded into the shell of hollow poly(lactic-co-glycolic)acid nanocarriers.The morphology,structure,particle size,and zeta potential of the h-PCuNF nanoparticles were characterized.In deionized water,the magnetic resonance imaging and photothermal conversion performances of the h-PCuNF nanoparticles,as well as their capability to implement reactive oxygen species production by mediating photocatalysis and Fenton-like reactions,were evaluated.In liver malignant tumor cell line HepG2 cells,the effectiveness of the photothermal therapy/photodynamic therapy/chemodynamic therapy/chemotherapy combination therapy mediated by the nanoparticles was detected by employing fluorescence imaging and MTT assay. RESULTS AND CONCLUSION:(1)The h-PCuNF nanoparticles possessed a hollow spherical structure in which the CuNPs(drug loading rate and encapsulation rate were 26.3%and 63.2%,respectively)and NF(drug loading rate and encapsulation rate were 11.0%and 52.6%,respectively)were loaded into the shell.The average particle size of the h-PCuNF nanoparticles was(309.2±10.0)nm,while the zeta potential was determined to be(-12.5±0.9)mV.In physiological environments,the nanoparticles possess favorable suspension stability.(2)In deionized water,the h-PCuNF nanoparticles could markedly enhance T1-weighted magnetic resonance imaging images.The h-PCuNF nanoparticles showed remarkable photothermal conversion and photocatalytic reactive oxygen species generation capabilities under near infrared laser irradiation.In addition,the h-PCuNF nanoparticles could consume glutathione and mediate Fenton-like reactions to produce·OH.(3)The h-PCuNF nanoparticles could be taken up by HepG2 tumor cells and were mainly distributed in the cytoplasm.The synergistic therapeutic effect was demonstrated after the nanoparticles were activated by near infrared laser irradiation,because CuNPs mediated photothermal therapy/photodynamic therapy/chemodynamic therapy and NF mediated chemotherapy could synergistically eliminate the tumor cells.

Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low-,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-α in serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and the serum contents of IL-1β,IL-6 and TNF-α in the model group significantly increased(P<0.01),the protein expressions of IL-1β,IL-6,TNF-α,TLR4 and p65 in breast tissue significantly increased(P<0.01),and the protein expression of IκBα significantly decreased(P<0.05).Compared with the model group,the erythema of the breasts of the rats in each treatment group was improved,and the extent of the lumps was reduced,and the reduction in the size of the lumps in the prednisolone group and the Yanghe Decoction high-dosage group was obvious(P<0.05).The inflammatory index score of prednisolone group and Yanghe Decoction groups decreased to different degrees(P<0.01),ultrasound showed a smaller range of hypoechoic area,pathology showed a reduction in the infiltration of inflammatory cells,and a reduction in the formation of granulomas and abscesses,and the prednisolone group and Yanghe Decoction groups significantly down-regulated the contents of IL-1β and TNF-α in serum(P<0.01),and the prednisolone group and Yanghe Decoction middle-and high-dosage groups significantly down-regulated the content of IL-6 in serum(P<0.05,P<0.01),the expression of TLR4 protein in breast tissue was significantly decreased in Yanghe Decoction high-dosage group(P<0.05),the expressions of IL-1β,IL-6,TNF-α and p65 proteins in prednisolone group and Yanghe Decoction groups were significantly decreased(P<0.05,P<0.01),and the expression of the protein of IκBα significantly increased(P<0.01).Conclusion Yanghe Decoction can reduce the inflammatory response in GLM rats,and its mechanism may be related to the inhibition of TLR4/NF-κB signalling pathway.

Objective To address the challenges in human-robot interaction control for lower limb rehabilitation exoskeletons by optimizing gait pattern design and compliance control strategies,thereby enhancing the safety,comfort,and precision of rehabilitation training.Methods Rhythmic dynamic movement primitives were utilized to generate personalized gait trajectories,combined with an admittance control strategy to design a trajectory tracking controller.This controller adjusted control parameters in real time to guide the user's gait towards the desired trajectory,reduce interaction torque,improve gait consistency,and ensure safety and effectiveness during rehabilitation training.Results Walking experiments with three participants using the lower limb rehabilitation exoskeleton demonstrated that,compared to transparent mode,the trajectory tracking mode reduced the root mean square error(RMSE)of hip and knee joint angle trajectories from 7.24° and 13.25° to 3.01° and 4.76°,respectively.The mean absolute error(MAE)decreased from 6.35° and 11.17° to 2.54° and 3.50°,respectively.The absolute mean interaction torque decreased from 3.55 N·m and 3.42 N·m to 2.80 N·m and 1.86 N·m.These results validated that the trajectory tracking controller significantly improved gait consistency and comfort.Conclusions The application of rhythmic dynamic movement primitives combined with compliance control strategies in lower limb rehabilitation exoskeletons shows great potential,providing patients with a safer and more personalized rehabilitation experience.

Objective To address the challenges in human-robot interaction control for lower limb rehabilitation exoskeletons by optimizing gait pattern design and compliance control strategies,thereby enhancing the safety,comfort,and precision of rehabilitation training.Methods Rhythmic dynamic movement primitives were utilized to generate personalized gait trajectories,combined with an admittance control strategy to design a trajectory tracking controller.This controller adjusted control parameters in real time to guide the user's gait towards the desired trajectory,reduce interaction torque,improve gait consistency,and ensure safety and effectiveness during rehabilitation training.Results Walking experiments with three participants using the lower limb rehabilitation exoskeleton demonstrated that,compared to transparent mode,the trajectory tracking mode reduced the root mean square error(RMSE)of hip and knee joint angle trajectories from 7.24° and 13.25° to 3.01° and 4.76°,respectively.The mean absolute error(MAE)decreased from 6.35° and 11.17° to 2.54° and 3.50°,respectively.The absolute mean interaction torque decreased from 3.55 N·m and 3.42 N·m to 2.80 N·m and 1.86 N·m.These results validated that the trajectory tracking controller significantly improved gait consistency and comfort.Conclusions The application of rhythmic dynamic movement primitives combined with compliance control strategies in lower limb rehabilitation exoskeletons shows great potential,providing patients with a safer and more personalized rehabilitation experience.

Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low-,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-α in serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and the serum contents of IL-1β,IL-6 and TNF-α in the model group significantly increased(P<0.01),the protein expressions of IL-1β,IL-6,TNF-α,TLR4 and p65 in breast tissue significantly increased(P<0.01),and the protein expression of IκBα significantly decreased(P<0.05).Compared with the model group,the erythema of the breasts of the rats in each treatment group was improved,and the extent of the lumps was reduced,and the reduction in the size of the lumps in the prednisolone group and the Yanghe Decoction high-dosage group was obvious(P<0.05).The inflammatory index score of prednisolone group and Yanghe Decoction groups decreased to different degrees(P<0.01),ultrasound showed a smaller range of hypoechoic area,pathology showed a reduction in the infiltration of inflammatory cells,and a reduction in the formation of granulomas and abscesses,and the prednisolone group and Yanghe Decoction groups significantly down-regulated the contents of IL-1β and TNF-α in serum(P<0.01),and the prednisolone group and Yanghe Decoction middle-and high-dosage groups significantly down-regulated the content of IL-6 in serum(P<0.05,P<0.01),the expression of TLR4 protein in breast tissue was significantly decreased in Yanghe Decoction high-dosage group(P<0.05),the expressions of IL-1β,IL-6,TNF-α and p65 proteins in prednisolone group and Yanghe Decoction groups were significantly decreased(P<0.05,P<0.01),and the expression of the protein of IκBα significantly increased(P<0.01).Conclusion Yanghe Decoction can reduce the inflammatory response in GLM rats,and its mechanism may be related to the inhibition of TLR4/NF-κB signalling pathway.

BACKGROUND:Studies have shown that there is a close association between spinal cord injury and ferroptosis,and that tetramethylpyrazine has the function of regulating redox reactions. OBJECTIVE:To investigate the regulatory effect of tetramethylpyrazine on ferroptosis in rats with spinal cord injury and its mechanism. METHODS:Thirty-six female specific pathogen-free Sprague-Dawley rats were randomly divided into sham-operated group,model group and tetramethylpyrazine group,with 12 rats in each group.Animal models of spinal cord injury were established using the modified Allen's method in the latter two groups.No treatment was given in the sham-operated group,while rats in the model and tetramethylpyrazine groups were given intraperitoneal injection of normal saline and tetramethylpyrazine solution,once a day,for 28 days. RESULTS AND CONCLUSION:The Basso,Beattie&Bresnahan Locomotor Rating Scale score in the tetramethylpyrazine group was lower than that in the sham-operated group but higher than that in the model group after 14,21,and 28 days of treatment(P＜0.05).After 28 days of treatment,hematoxylin-eosin staining showed that in the model group,the spinal cord tissue of rats showed cavity formation,necrotic tissue and inflammatory infiltration with fibrous tissue formation;in the tetramethylpyrazine group,the area of spinal cord tissue defects was smaller,and inflammatory infiltration and fibrous tissue formation were less than those in the model group.After 28 days of treatment,Prussian blue staining showed that a large amount of iron deposition was seen in the spinal cord tissue of rats in the model group,and less iron deposition was seen in the spinal cord tissue of rats in the tetramethylpyrazine group than in the model group.After 28 days of treatment,the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were decreased(P＜0.05)and the level of malondialdehyde was increased in the model group compared with the sham-operated group(P＜0.05);the levels of glutathione and superoxide dismutase in the rat spinal cord tissue were increased(P＜0.05)and the level of malondialdehyde was decreased in the tetramethylpyrazine group compared with the model group(P＜0.05).After 28 days of treatment,qRT-PCR and western blot assay showed that the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the model group were decreased compared with those in the sham-operated group(P＜0.05),while the mRNA and protein levels of glutathione peroxidase 4,ferritin heavy chain,and ferroportin in the rat spinal cord tissue in the tetramethylpyrazine group were increased compared with those in the model group(P＜0.05).Immunofluorescence staining showed that after 28 days of treatment,the neuronal nuclei positive staining in the spinal cord of rats was the most in the sham-operated group and the least in the model group.To conclude,tetramethylpyrazine can improve motor function and play a neuroprotective role in rats with spinal cord injury by regulating ferroptosis.

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

Objective To explore the relationship between ultrasonographic characteristics and promoting angiogenesis related genes in breast invasive ductal carcinoma.Methods A search was conducted in the PubMed database to identify genes related to promoting an-giogenesis in breast cancer.Protein-protein interaction networks(PPI)were constructed using the STRING database and Cytoscape soft-ware,and screen for key genes.A total of 38 female patients diagnosed with breast invasive ductal carcinoma from January 2022 to August 2023 were included in the study.The relationship between clinical and ultrasonographic characteristics of these patients and key genes was analyzed.Results A total of 10 key genes were screened.The expression levels of TGF-β1 and CXCL12 in patients aged＞50 years were higher than those in patients aged ≤50 years(P＜0.05).The expression level of IL-6 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis(P＜0.05).The expression level of CCL2 in patients with color pixel percent-age(CPP)of ultra micro angiography(UMA)＞10％was higher than that in patients with CPP of UMA ≤10％(P＜0.05).The ex-pression level of Akt1 in patients with predominantly peripheral vascular distribution were higher than that in patients with central distribu-tion(P＜0.05).The expression levels of IL-6,TGF-β1,PEC AM1,CXCL8 and CXCL12 in patients with uneven contrast perfusion were higher than those in patients with even contrast perfusion(P＜0.05).The expression levels of TGF-β1,PEC AM1,FN1 and CX-CL12 in patients with contrast perfusion defect area＞1/2 were higher than those in patients with contrast perfusion defect area≤1/2(P＜0.05).There was a correlation among genes involved in regulating contrast perfusion uniformity and perfusion defect area,particu-larly the intersecting genes TGF-β1,PECAM1 and CXCL12(P＜0.05).Conclusion There is a correlation between the ultrasono-graphic characteristics of breast invasive ductal carcinoma and key genes related to promoting angiogenesis,which may provide a reference for individualized treatment of breast cancer.

Objective To investigate the effect of transcutaneous electrical acupoint stimulation(TEAS)on emergence agitation(EA)in children undergoing selective posterior rhizotomy(SPR).Methods Forty-two children with cerebral palsy undergoing SPR were selected,20 males and 22 females,aged 6-12 years,BMI 13-24 kg/m2,ASA physical status Ⅰ or Ⅱ,randomly divided into two groups:TEAS group(group T)and control group(group C),21 children in each group.Children in group T re-ceived TEAS at the bilateral acupoints of Neiguan and Hegu from 30 minutes before anesthesia induction to the end of surgery.In group C,electrodes were placed on the same acupoints without electrical stimulation.All children in both groups received total intravenous anesthesia.HR and MAP were recorded at the time of entry,extubation,5,15,30 minutes after extubation.The consumption of remifentanil and propofol during the procedure were recorded.The time of operation and extubation were recorded.The Wong-Baker faces pain scale-revised(FPS-R)and the pediatric anesthesia emergence delirium(PAED)were recorded at 15 minutes after extubation,and the incidence of EA was assessed by PAED.While,the occurrence of post-operative nausea and vomiting(PONV)was recorded.Results Compared with that at the time of entry,HR at the time of extubation,5,15 minutes after extubation and MAP at the time of extubation,5,15,30 minutes after extubation in group C were significantly increased(P＜0.05),HR and MAP at the time of extubation,5,15 minutes after extubationin group T were significantly increased(P＜0.05).Compared with group C,HR was significantly slower and MAP was significantly lower in group T at the time of extuba-tion,5,15,30 minutes after extubation(P＜0.05).Compared with group C,the consumption of remifen-tanil during operation was reduced,the time of extubation was significantly shortened,the FPS-R and PAED were significantly decreased,and the incidence of EA were significantly reduced(P＜0.05).There were no significant differences in the time of operation,the consumption of propofol during operation and the inci-dence of PONV.Conclusion TEAS is beneficial to prevent the occurrence of EA in pediatric patients un-dergoing SPR,stabilize hemodynamics,reduce the dosage of opioids during surgery,reduce the postopera-tive pain,andaccelerate the time of anesthesia resuscitation.

Objective To explore the prognostic value of MCF in elderly patients with cardiac amy-loidosis using CMR.Methods A retrospective analysis was conducted on 54 elderly patients with cardiac amyloidosis diagnosed in our hospital.All patients underwent CMR imaging.They were di-vided into a survival group of 25 cases and a mortality group of 29 cases based on clinical out-comes.Correlations of MCF with CMR parameters and biochemical indicators were evaluated.Cox regression analysis was performed to identify independent predictors of patient survival.Survival analysis was used to assess the value of MCF in predicting patient prognosis.Results The surviv-al group had significantly higher MCF than the mortality group[(70.63±24.72)％vs(43.59± 13.36)％,P=0.001].As MCF increasing,LVEF level was in an increasing trend,while LVMI,LVGPWT,ECV,and troponin T and NT-proBNP levels showed a decreasing trend.Multivariate Cox regression analysis revealed that MCF was an independent predictor of patient survival(HR=0.922,95％CI:0.866-0.981,P=0.011).Kaplan-Meier survival curve showed that the patients with MCF＞57％had significantly higher survival rates than those with MCF ≤57％(P＜0.01).Conclusion MCF is an effective imaging indicator for evaluating the prognosis of elderly patients with cardiac amyloidosis,which can help identify high-risk patients and guide clinical treatment.