OBJECTIVE To investigate the neuroprotective effect and mechanism of eleutheroside B （ELB） on Parkinson’s disease （PD） model mice by regulating the IκB kinase β （IKKβ）/nuclear factor-κB （NF-κB） signaling pathway. METHODS Fifty mice were randomly divided into normal control group， model group， positive control group （selegiline hydrochloride， 10 mg/kg）， and ELB low-dose and high-dose groups （80， 160 mg/kg）， with 10 mice in each group. Each group was given relevant medicine or normal saline intragastrically for 14 consecutive days. Starting from the 10th day of administration， the model group and all administration groups were intraperitoneally injected with 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP） 30 mg/kg， for five consecutive days to establish the chronic PD model. After the last administration for 24 h， six mice were randomly selected from each group to test their behavioral abilities； detect the levels of interleukin-1β （IL-1β）， IL-10， tumor necrosis factor-α （TNF-α） in brain tissue and their mRNA expressions were measured， and positive expression of tyrosine hydroxylase （TH）， protein expressions of TH， α -synuclein （ α -syn）， ionized calcium-binding adaptor molecule 1 （Iba-1）， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in the brain tissue were detected. The ultrastructure of neurons in substantia nigra was observed. RESULTS Compared with the model group， rotarod endurance time and climbing score of each administration group （except for the ELB low-dose group） were increased significantly （ P ＜0.05）， while the levels and mRNA expressions of IL-1β， TNF-α， α -syn， and Iba-1， as well as phosphorylation levels of IKKβ and NF-κB p65 proteins in brain tissue were decreased significantly （except for TNF-α in the ELB low-dose group）. Conversely， the level and mRNA expression of IL-10 （except for the ELB low-dose group）， TH positive expression and protein expressions were significantly increased （ P ＜0.05）. Typical neurodegenerative pathological changes， such as neuronal karyopyknosis， mitochondrial swelling and vacuolization， and endoplasmic reticulum dilation， all showed varying degrees of improvement. CONCLUSIONS ELB may exert neuroprotective effects by inhibiting the activation of the IKKβ/NF-κB signaling pathway， alleviating inflammatory responses， reducing abnormal α -syn aggregation and neuronal loss， and further improving motor dysfunction in PD mice.

OBJECTIVES: To elucidate the underlying mechanisms of macrophage-mediated inflammation and tissue injury in diabetic foot ulcer (DFU). METHODS: Skin tissue samples were collected from patients with DFU and with non-DFU. A total of 79 272 high-quality cell transcriptomes were obtained using single-cell RNA sequencing. An unbiased clustering approach was employed to identify cell subpopulations. Seurat functions were used to identify differentially expressed genes between DFU and non-DFU groups, and gene ontology (GO) enrichment analysis was used to reveal gene function. Furthermore, cell-cell communication network construction and ligand-receptor interaction analysis were performed to reveal the mechanisms underlying cellular interactions and signaling regulation in the DFU microenvironment from multiple perspectives. RESULTS: The results revealed a significant expansion of myeloid cells in DFU tissues, alongside a marked reduction in structural cells such as endothelial cells, epithelial cells, and smooth muscle cells. Major cell types underwent functional reprogramming, characterized by immune activation and impaired tissue remodeling. Specifically, macrophages in DFU skin tissues exhibited a shift toward a pro-inflammatory M1 phenotype, with upregulation of genes associated with inflammation and oxidative stress. Cell communication analysis further demonstrated that M1 macrophages served as both primary signal receivers and influencers in the COMPLEMENT pathway mediated communication network, and as key signal senders and mediators in the secreted phosphoprotein 1 (SPP1) pathway mediated communication network, actively shaping the inflammatory microenvironment. Key ligand-receptor interactions driving macrophage signaling were identified, including C3-(ITGAM+ITGB2) and SPP1-CD44. CONCLUSIONS This study establishes a comprehensive single-cell atlas of DFU, revealing the role of macrophage-driven cellular networks in chronic inflammation and impaired healing. These findings may offer potential novel therapeutic targets for DFU treatment.
Humans ; Macrophages/immunology* ; Diabetic Foot/pathology* ; Single-Cell Analysis ; Transcriptome ; Gene Expression Profiling ; Inflammation ; Skin ; Cell Communication ; Signal Transduction ; Cellular Reprogramming

Objective To investigate the prevalence of specific IgE antibodies against Alternaria alternata and Aspergillus fumigatus in serum samples from clinical allergy patients across selected provinces in China.Methods Data on specific IgE antibodies for Alternaria A.and Aspergillus F.were collected from 20 hospital laboratories in 17 cities spanning 11 provinces.The study analyzed the levels of specific IgE and their variations across different provinces and seasons.Results A total of 27 471 cases of Alternaria A.and 32 843 cases of Aspergillus F.specific IgE data were included.The national average positive rate of Alternaria A.IgE was 10.40%,with the highest rate of 22.68%in Jiangsu and the lowest rate of 2.06%in Guangxi.For Aspergillus F.specific IgE,the average positive rate was 4.24%,with Hubei province having the highest rate(7.25%)and Hunan province the lowest(1.23%).The difference in IgE levels for both Alternaria A.and Aspergillus F.among provinces were statistically significant(H=9 955,16 993,all P<0.0001).Among patients,5.85%had Alternaria A.specific IgE levels at grade 3 or above,while only 0.57%had Aspergillus F.specific IgE levels at this level.When examining seasonal variations using data from Liaoning,Hunan and Anhui provinces,significant seasonal changes were observed for both Alternaria A.and Aspergillus F.IgE antibodies(HAlternaria A=347.6,338.0,401.3,HAspergillus F=196.6,133.7,231.7,all P<0.0001).Conclusion The sensitization to Alternaria A.and Aspergillus F.exhibits distinct geographical characteristics and vary significantly with seasons.Given the relatively high IgE levels associated with Alternaria A.,it should be given adequate clinical attention.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Purpose Based on multimodal imaging combined with a variety of histological techniques,to visually evaluate the changes of rats brain metabolic microenvironment after cerebral hypoxia and ischemia of prematurity,and to discuss the effects of abnormal lactate metabolism in the brain on oligodendrocyte precursor cells,so as to provide a basis for the early diagnosis and treatment of premature white matter injury(PWMI).Materials and Methods A total of 36 SPF-grade healthy 3-day-old Sprague-Dawley neonatal rats were randomly assigned to the sham surgery(Sham)group and the model(PWMI)group using a random number table method,with 18 rats in each group.A neonatal rat PWMI model was established by hypoxia-ischemia method.Twenty-four hours after modeling,laser speckle imaging was used to monitor cerebral blood flow and blood oxygen changes.Multimodal imaging was used to observe the changes in brain tissue microstructure and metabolism after PWMI.HE staining was used to observe the morphological changes of nerve cells in the white matter of the brain.Enzyme-linked immunosorbent assay was used to detect the changes of lactate content and lactate dehydrogenase activity in the white matter region of the brain after PWMI in neonatal rats.PDGFR-α immunofluorescence staining was used to observe the dynamic changes of the number of oligodendrocyte precursor cells in the subependymal zone after PWMI in neonatal rats.Results Twenty-four hours after modeling,the multimodal imaging results showed that the T2WI and diffusion-weighted imaging on the injured side of the PWMI group showed high intensity,and the relative cerebral blood flow,relative oxygen saturation,relative apparent diffusion coefficient and amide proton transfer(APT)Lorentzian difference value were lower than those in the Sham group(t=29.466,23.522,59.006,54.778,10.263,all P<0.001),and the lactate content was higher than that in the Sham group(t=-7.521,P<0.001).The results of HE staining and enzyme-linked immunosorbent assay showed that the arrangement of nerve cells in the white matter area of the injured side of the brain in the PWMI group was loose and disordered.The lactate content and lactate dehydrogenase activity were higher than those in the Sham group(t=-6.079,-10.548,both P<0.001).The results of immunofluorescence staining showed that the number of PDGFR-α+cells in the subependymal zone of the damaged side of the PWMI group was higher than that of the Sham group at 24 hours after modeling,and lower than that in the Sham group at 11 days after modeling(t=-8.386,6.676,both P<0.001).The correlation analysis between the lactate content and APT Lorentzian difference value in the brain and the number of oligodendrocyte precursor cells in the brain 11 days after modeling showed that the number of oligodendrocyte precursor cells in the subependymal zone was positively correlated with the APT Lorentzian difference value(r=0.821,P=0.001 1),and negatively correlated with the lactate content in the brain(r=-0.880,P=0.000 2).Conclusion Multimodal imaging can monitor the early brain metabolism changes of PWMI in neonatal rats,especially the changes of lactate,and provide a visual basis for their early diagnosis.The level of lactate in the brain increases after cerebral hypoxia and ischemia in prematurity,and oligodendrocyte precursor cells increase transiently and then decrease,resulting in PWMI.

Objective:To design one kind of adjustably assistive walking wheelchair with multi postures,so as to improve the quality of life of people with motion disorders,disabilities or semi disabilities on lower limbs.Methods:The adjustably assistive walking wheelchair with multi postures composed of walking mechanism,mechanism of adjusting posture,and chair,which can achieve five postures,including sitting,low sitting,high sitting,standing and lying.One kinematic model of the wheelchair mechanism was established,and Admas software was used to conduct kinematic simulation.Aimed at key components,the statics simulation was analyzed.The test for adjustment of 5 kinds of postures,the test for the reachable range of hands and the test for the stability of adjusted postures were conducted on the physical prototype of the wheelchair.Results:The results of kinematic simulation showed that the method and formula derivation of motion analysis were correct.Static simulation showed that the seat cushion bracket of key load-bearing component did not affect the normal use of wheelchair under the effect of 100 kg load on seat posture.Experimental tests showed that all parameters of posture transformation were consistent with the design objectives and theoretical analysis.The reachable range of hands was between 500 mm and 2300 mm.The tested results of transformation between sitting and lying postures showed that the stability of the system of adjusting posture of wheelchair was favorable.Conclusion:The adjustably assistive walking wheelchair with multi postures can meet the requirement of user in getting things at low and high position through adjusts the height of sitting posture,which can suit the requirement of user at different home scenarios with larger difference at height,such as table,stove and cabinet.

Thyroid diseases are clinically prevalent endocrine and metabolic disorders, including various types such as Hashimoto's thyroiditis and thyroid nodules. Their pathogenesis is complex and influenced by numerous factors, potentially involving genetic factors, environmental factors, and immune dysfunction. With the continuous advancement of modern traditional Chinese medicine (TCM), TCM has established a unique theoretical system in the prevention and treatment of thyroid diseases, with increasingly rich clinical practical experience. This article reviews the recent application of TCM health status analysis, monitoring, early warning, and prevention in the field of thyroid diseases, aiming to provide useful references for in-depth study in this field.

Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

Transient perivascular inflammation of the carotid artery(TIPIC)syndrome is a relatively rare disease,and ultrasound is the first screening method for initial diagnosis of the disease.Contrast-enhanced ultrasound(CEUS)has unique advantages in the follow-up of patients with TIPIC syndrome.This paper reports a patient with TIPIC syndrome who was treated with acute left neck pain.The inflammation was significantly re-lieved and subsided after treatment with non-steroidal anti-inflammatory drugs.The ultrasound changes of carotid artery lesions in this patient during follow-up were analyzed,and the application value of CEUS in the follow-up diagnosis of this disease was summarized,in the hope of providing clinical reference.