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.

BACKGROUND:In China,the patient population with osteonecrosis is large,and there is an urgent need to find new preventive targets to develop more effective treatment strategies.Metabolomics studies have shown that there is an association between human metabolites and osteonecrosis,but the causal relationship between blood metabolites and osteonecrosis has not yet been clarified.OBJECTIVE:To investigate the causal relationship between blood metabolites and osteonecrosis through two-sample Mendelian randomization analysis.METHODS:The public data of 486 blood metabolites(exposure factors)and osteonecrosis(outcome factors)were collected.Data of 486 blood metabolites were derived from a genome-wide association estimate for blood metabolites published in Nature Genetics in 2014,which covered 7 824 European adults.The single nucleotide polymorphism data for osteonecrosis were obtained from the FinnGen public database R11 dataset,containing information on a total of 431 614 samples and 21 306 430 single nucleotide polymorphism loci,with 1 788 cases of osteonecrosis and 429 826 controls,with all participants being of European descent.Mendelian randomization analysis(inverse variance weighting method,MR-Egger method,and weighted median method)was performed by Rstudio software,and then the heterogeneity test,horizontal pleiotropy test and Steiger directionality test were performed to ensure the robustness and reliability of the results.RESULTS AND CONCLUSION:(1)Sixteen blood metabolites were identified as having a significant causal relationship with osteonecrosis(Pinverse variance weighting＜Pfalse discovery rate＜0.05).(2)Eight blood metabolites increased the risk of osteonecrosis(including four known metabolites and four unknown metabolites),specifically pantothenate,beta-hydroxyisovalerate,hippurate,salicyluric glucuronide,X-08766,X-11452,X-12776 and X-14662.(3)Eight blood metabolites could reduce the risk of osteonecrosis(six known metabolites and two unknown metabolites),including cortisol,1-palmitoylglycerol(1-monopalmitin),pyroglutamyl glycine,2-stearoylglycerophosphocholine,p-cresol sulfate,ergothioneine,X-06307,X-12092.(4)The above results suggest that there is a causal relationship between 16 blood metabolites and osteonecrosis,which is expected to be a potential target for intervention in the occurrence and treatment of osteonecrosis in the future.(5)Despite the lack of relevant data from large-scale Asian populations at present,this study provides important reference value for the field of osteonecrosis in China based on European population data.In the future,domestic medical workers may be able to achieve precise intervention for osteonecrosis by regulating metabolite levels.In addition,based on the results of this study,relevant researchers can further explore the mechanism of action of metabolites in the treatment of osteonecrosis with traditional Chinese medicine,which not only helps to deepen the understanding of traditional Chinese medical therapies but also promotes the progress of integrated traditional Chinese and Western medicine research,driving the development of personalized treatment plans that are more suitable for the characteristics of the Chinese population.

BACKGROUND:In China,the patient population with osteonecrosis is large,and there is an urgent need to find new preventive targets to develop more effective treatment strategies.Metabolomics studies have shown that there is an association between human metabolites and osteonecrosis,but the causal relationship between blood metabolites and osteonecrosis has not yet been clarified.OBJECTIVE:To investigate the causal relationship between blood metabolites and osteonecrosis through two-sample Mendelian randomization analysis.METHODS:The public data of 486 blood metabolites(exposure factors)and osteonecrosis(outcome factors)were collected.Data of 486 blood metabolites were derived from a genome-wide association estimate for blood metabolites published in Nature Genetics in 2014,which covered 7 824 European adults.The single nucleotide polymorphism data for osteonecrosis were obtained from the FinnGen public database R11 dataset,containing information on a total of 431 614 samples and 21 306 430 single nucleotide polymorphism loci,with 1 788 cases of osteonecrosis and 429 826 controls,with all participants being of European descent.Mendelian randomization analysis(inverse variance weighting method,MR-Egger method,and weighted median method)was performed by Rstudio software,and then the heterogeneity test,horizontal pleiotropy test and Steiger directionality test were performed to ensure the robustness and reliability of the results.RESULTS AND CONCLUSION:(1)Sixteen blood metabolites were identified as having a significant causal relationship with osteonecrosis(Pinverse variance weighting＜Pfalse discovery rate＜0.05).(2)Eight blood metabolites increased the risk of osteonecrosis(including four known metabolites and four unknown metabolites),specifically pantothenate,beta-hydroxyisovalerate,hippurate,salicyluric glucuronide,X-08766,X-11452,X-12776 and X-14662.(3)Eight blood metabolites could reduce the risk of osteonecrosis(six known metabolites and two unknown metabolites),including cortisol,1-palmitoylglycerol(1-monopalmitin),pyroglutamyl glycine,2-stearoylglycerophosphocholine,p-cresol sulfate,ergothioneine,X-06307,X-12092.(4)The above results suggest that there is a causal relationship between 16 blood metabolites and osteonecrosis,which is expected to be a potential target for intervention in the occurrence and treatment of osteonecrosis in the future.(5)Despite the lack of relevant data from large-scale Asian populations at present,this study provides important reference value for the field of osteonecrosis in China based on European population data.In the future,domestic medical workers may be able to achieve precise intervention for osteonecrosis by regulating metabolite levels.In addition,based on the results of this study,relevant researchers can further explore the mechanism of action of metabolites in the treatment of osteonecrosis with traditional Chinese medicine,which not only helps to deepen the understanding of traditional Chinese medical therapies but also promotes the progress of integrated traditional Chinese and Western medicine research,driving the development of personalized treatment plans that are more suitable for the characteristics of the Chinese population.

ObjectiveTo explore the factors influencing home-based rehabilitation exercise and the needs for digital interventions among patients with spinal muscular atrophy (SMA), based on the behavior change wheel (BCW), and to provide evidence for the development of digital home-based rehabilitation interventions. MethodsA two-phase qualitative study was conducted from December, 2024 to March, 2025. Using convenience sampling, 14 participants were recruited, including patients with SMA, primary caregivers, rehabilitation professionals, clinicians, a patient organization representative and a health policy expert. In phase 1, semi-structured individual interviews were conducted with seven participants, including patients, caregivers and a patient organization representative, to identify factors influencing home-based rehabilitation exercise and unmet needs. In phase 2, a focus group involving 12 stakeholders was conducted, including five participants who had participated in phase 1, to explore requirements for the functions, knowledge content and interface design of a digital intervention, five of them had participated in phase 1. Overall, the two phases involved 14 individual participants, accounting for 19 participant-instances. Thematic analysis was performed using both deductive and inductive approaches, guided by the capability-opportunity-motivation-behavior (COM-B) model. ResultsSix themes were identified. phase 1 showed that patients with SMA experienced inadequate continuity of rehabilitation services and limited access to professional rehabilitation resources, with interruptions in institution-based rehabilitation coexisting with declining adherence to home-based exercise. Home-based rehabilitation exercise was jointly influenced by capability-, opportunity- and motivation-related factors, including limited capabilities of patients and caregivers, constraints in time and supportive conditions and insufficient goals, feedback, and incentives. Individualized rehabilitation plans and professional guidance were the major unmet needs. phase 2 showed that the core functions of a digital intervention should include individualized exercise plans, professional guidance and feedback, reminders and incentives, safety monitoring, remote assessment, and privacy and permission management. Core knowledge content should include stratified exercise guidance, caregiving skills, recognition of abnormal conditions, and information on when and how to seek help. The interface should be simple, impose a low user burden and accommodate different types of users. ConclusionHome-based rehabilitation exercise among patients with SMA is jointly influenced by multiple capability-, opportunity- and motivation-related factors. Digital interventions should prioritize individualized rehabilitation plans, professional guidance and sustained behavioral support. These findings may inform the development of a digital home-based rehabilitation intervention prototype for patients with SMA; its feasibility, safety, clinical effectiveness and economic value require further evaluation.

Objective To analyze the effect of topical recombinant human acidic fibroblast growth factor(rh-aFGF)on wound healing in burn and scald patients.Methods A total of 240 burn pa-tients were selected as the study subjects and divided into observation group and control group,with 120 cases in each group.The control group was treated with compound polymyxin B ointment,while the observation group received rh-aFGF combined with compound polymyxin B ointment.The wound healing time,wound healing rate,positive detection rate of wound pathogens and wound inflammatory response were compared between the two groups after treatment.Results After 28 days of medication,the wound healing time of patients in the observation group was significantly shorter,and the wound healing rate was significantly higher than that in the control group(P＜0.05).The detection rate of pathogens in the burn wounds of the observation group was significantly lower than that of the control group at 7,14,21,and 28 days after treatment(P＜0.05).There was a statistically significant differ-ence in wound inflammatory response between the two groups(P＜0.05).Conclusion The rh-aFGF is effective in treatment of burn and scald wound,and it is conductive to promoting wound healing,shortening healing time,and reducing wound inflammatory responses.

Objective:To explore the diagnostic value of transvaginal color Doppler sonography (TVCDS) combined with serum allograft inflammatory factor-1 (AIF-1) and pyruvate kinase M2 type (PKM2) in cervical cancer.Methods:From Jan. 2022 to Jun. 2024, 168 patients with early cervical cancer who visited Taizhou Central Hospital were regarded as the cervical cancer group, and 96 patients with cervical precancerous lesions were regarded as the precancerous lesion group. All patients underwent TVCDS examination to obtain parameters such as peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI). ELISA method was used to detect serum AIF-1 and PKM2 levels. Kappa test was used to analyze the consistency between different diagnostic methods and pathological results. ROC curve was used to analyze the diagnostic value of serum AIF-1 and PKM2 levels for cervical cancer.Results:The cervical cancer group had manifestly higher proportions of irregular morphology, unclear boundaries, low echo ratio, and levels of PSV, EDV, AIF-1, and PKM2 than precancerous lesion group, and manifestly lower RI than precancerous lesion group ( P<0.05). The consistency analysis between TVCDS diagnosis of cervical cancer and pathological results showed a Kappa value of 0.674 ( P<0.05). The serum levels of AIF-1 and PKM2 in cervical cancer patients with a maximum tumor diameter of ≥ 4 cm, low differentiation, and vaginal infiltration were manifestly higher than those in patients with a maximum tumor diameter of < 4 cm, medium/high differentiation, and non vaginal infiltration ( P<0.05). The AUC of AIF-1 and PKM2 in the diagnosis of cervical cancer was 0.824 and 0.816, respectively, with diagnostic thresholds of 81.21 ng/L and 29.26 ng/mL. The consistency analysis of TVCDS combined with serum AIF-1 and PKM2 in the diagnosis of cervical cancer and pathological results showed a Kappa value of 0.918 ( P<0.05). The negative predictive value, accuracy, and sensitivity of TVCDS combined with serum AIF-1 and PKM2 in the diagnosis of cervical cancer were higher than those of each indicator alone, and the positive predictive value and specificity were higher than those of AIF-1 alone ( P<0.05) . Conclusion:TVCDS combined with serum AIF-1 and PKM2 has high accuracy and sensitivity in the diagnosis of cervical cancer, and their combination can serve as a potential method for clinical diagnosis of cervical cancer.

Objective To investigate the impact of sleep modes on the risk for diseases of the body systems.Methods Based on a subset of UK Biobank dataset comprising 87 617 participants,3 sleep dimensions including 6 sleep indicators were obtained through a wrist-worn accelerometer,that is sleep duration and onset,sleep rhythm(relative amplitude and stability),and sleep quality(sleep efficiency and number of awakenings).Latent profile analysis(LPA)was applied to identify and classify distinct sleep modes.Then their longitudinal medical records were the association between different sleep modes and the risk for 467 diseases.Results LPA identified 5 subgroups of unique sleep modes in the participants.Among the 5 subgroups,the subgroup 4 had relatively optimal levels in above sleep indicators.Compared to the subgroup 4,the other 4 subgroups exhibited variations in different sleep dimensions,with at least one indicator demonstrating an unfavorable trend.These subgroups also revealed differences in racial composition,shift work and social deprivation index.Moreover,there were notable differences in the risk of various system diseases among the subgroups(P<0.05).When compared to the subgroup 4,the other 4 subgroups exhibited an elevated risk for certain diseases(comprising a total of 126 diseases),with the diseases of the circulatory system,digestive system and musculoskeletal system most common.Among the 5 subgroups,the subgroup 2(shorter sleep duration and later sleep onset)and the subgroup 5(rhythm disorder)had the highest counts of associated risks,amounting to 85 and 91 types,respectively,but there was certain difference in their systematic composition.Conclusion There are different sleep modes within the participants,and the modes are potentially associated with an increased risk for diseases of body systems.Comprehensive interventions targeting overall sleep modes rather than single sleep indicator may yield obvious health benefits.

Immune thrombocytopenia (ITP) is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury. ITP has complicated immunopathological mechanisms that need further elucidation. It is well known that the costimulatory molecules OX40 ligand (OX40L) and OX40 play essential roles in the immunological mechanisms of autoimmune diseases. Previously, we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells (PBMCs) of ITP patients. In our present study, OX40L-induced follicular helper T (Tfh) cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PD-1), and cluster of differentiation 40 ligand (CD40L) in vitro. Moreover, aberrant OX40L‒OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo, inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model, which might accelerate the progression of ITP. Additionally, signal transduction through the OX40L‒OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor (TRAF)‒nuclear factor-κB (NF-κB) and Janus kinase (JAK)‒signal transducer and activator of transcription (STAT) signaling pathways. Overall, OX40L‒OX40 signaling is proposed as a potential novel therapeutic target for ITP.
Animals ; OX40 Ligand/physiology* ; Purpura, Thrombocytopenic, Idiopathic/immunology* ; Cell Differentiation ; Mice ; T-Lymphocytes, Helper-Inducer/cytology* ; T Follicular Helper Cells/cytology* ; Signal Transduction ; Receptors, OX40 ; Mice, Inbred C57BL ; Humans ; Female

Disruption of normal secretion or mucociliary clearance can impair airway defense mechanisms and lung function, and increase the risk of infection. Airway clearance techniques are recommended as part of a comprehensive treatment plan for patients. Among these, vibratory expectoration is an important method of airway clearance, which loosens and liquefies mucus and metabolites on the surface of the respiratory tract through chest wall oscillation, promoting ciliary movement to facilitate sputum expulsion. However, commonly used handheld vibrating head devices and vest-type vibration expectorators have several limitations in clinical practice, such as inconvenience of operation, limited treatment time, poor adaptability, and difficulty in disinfection. To address these issues, the research team from the department of critical care medicine at Ruijin Hospital, Shanghai Jiao Tong University, has designed a novel belt-type vibration expectorator, which has been granted a national utility model patent (Patent No.: ZL 2023 2 1610983.1). The device is mainly composed of a chest strap assembly, a sputum clearance component, and a fixed shoulder strap component. Several pockets are placed on the outer surface of the chest strap, with corresponding inner-side openings that allow the percussion head of the percussive expectorator placed inside the pocket to make contact with the patient's chest wall. Each pocket has markings indicating the percussion position, enabling the placement of the percussive expectorator according to the location of infection, thereby achieving multi-point, precise percussive vibration expectoration in different body positions. On the inner side of the chest strap, there are diagrams illustrating postural drainage, providing guidance on the body positions patients should assume based on the location of infection. The hook-and-loop fasteners on both sides of the chest strap can be wrapped around and secured according to the patient's body shape, ensuring that the sputum clearance components adhere tightly to the chest wall, allowing the vibrations generated by percussion to be effectively transmitted to the patient's airways. Additionally, to prevent the chest strap from slipping due to changes in the patient's position, a Y-shaped fixing strap can be selectively attached to the chest strap for further stabilization. This innovation not only simplifies the operation process, improves convenience and flexibility of use, but also supports the principle of "disinfection after each use by one person," which helps to reduce the risk of nosocomial infections and improve the efficiency of patients' respiratory rehabilitation.
Humans ; Vibration ; Equipment Design ; Chest Wall Oscillation/instrumentation* ; Sputum ; Expectorants ; Mucociliary Clearance

Objective:To explore the diagnostic value of transvaginal color Doppler sonography (TVCDS) combined with serum allograft inflammatory factor-1 (AIF-1) and pyruvate kinase M2 type (PKM2) in cervical cancer.Methods:From Jan. 2022 to Jun. 2024, 168 patients with early cervical cancer who visited Taizhou Central Hospital were regarded as the cervical cancer group, and 96 patients with cervical precancerous lesions were regarded as the precancerous lesion group. All patients underwent TVCDS examination to obtain parameters such as peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI). ELISA method was used to detect serum AIF-1 and PKM2 levels. Kappa test was used to analyze the consistency between different diagnostic methods and pathological results. ROC curve was used to analyze the diagnostic value of serum AIF-1 and PKM2 levels for cervical cancer.Results:The cervical cancer group had manifestly higher proportions of irregular morphology, unclear boundaries, low echo ratio, and levels of PSV, EDV, AIF-1, and PKM2 than precancerous lesion group, and manifestly lower RI than precancerous lesion group ( P<0.05). The consistency analysis between TVCDS diagnosis of cervical cancer and pathological results showed a Kappa value of 0.674 ( P<0.05). The serum levels of AIF-1 and PKM2 in cervical cancer patients with a maximum tumor diameter of ≥ 4 cm, low differentiation, and vaginal infiltration were manifestly higher than those in patients with a maximum tumor diameter of < 4 cm, medium/high differentiation, and non vaginal infiltration ( P<0.05). The AUC of AIF-1 and PKM2 in the diagnosis of cervical cancer was 0.824 and 0.816, respectively, with diagnostic thresholds of 81.21 ng/L and 29.26 ng/mL. The consistency analysis of TVCDS combined with serum AIF-1 and PKM2 in the diagnosis of cervical cancer and pathological results showed a Kappa value of 0.918 ( P<0.05). The negative predictive value, accuracy, and sensitivity of TVCDS combined with serum AIF-1 and PKM2 in the diagnosis of cervical cancer were higher than those of each indicator alone, and the positive predictive value and specificity were higher than those of AIF-1 alone ( P<0.05) . Conclusion:TVCDS combined with serum AIF-1 and PKM2 has high accuracy and sensitivity in the diagnosis of cervical cancer, and their combination can serve as a potential method for clinical diagnosis of cervical cancer.