OBJECTIVE:Repetitive transcranial magnetic stimulation and transcranial direct current stimulation have shown positive effects in improving gross motor function in children with cerebral palsy.A network meta-analysis was performed to analyze the clinical efficacy of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on the improvement of lower limb motor function and gait in children with cerebral palsy.METHODS:Randomized controlled trials(RCT)about repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor function and gait in children with cerebral palsy were collected from CNKI,WanFang,VIP,SinoMed,PubMed,Web of Science,Medline.The search time limit was from the inception to October 5,2024.After screening literature,extracting data and evaluating the risk of bias of included studies,Stata 15.0 software was used for network meta-analysis,AND GRADE profiler was used for quality evaluation.RESULTS:A total of 19 studies were included,involving 4 treatment measures:conventional therapy,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation and anodic transcranial direct current stimulation.The results of network meta-analysis showed that in terms of improving gross motor function,low-frequency repetitive transcranial magnetic stimulation[mean difference(MD)=9.48,95％confidence interval(CI)(6.61,12.34),P＜0.05]was the most effective.In terms of alleviating spasticity,high-frequency repetitive transcranial magnetic stimulation[MD=-0.63,95％CI(-1.72,0.45),P＜0.05]had the best efficacy.In terms of improving ankle joint range of motion and step speed,transcranial direct current stimulation[MD=2.27,95％CI(1.37,3.17),P＜0.05;MD=0.11,95％CI(0.05,0.17),P＜0.05]was the most effective.CONCLUSION:Existing clinical evidence suggests that low-frequency repetitive transcranial magnetic stimulation has the best therapeutic effect compared with other intervention measures in terms of improving lower limb gross motor function.In terms of reducing spasticity,high-frequency repetitive transcranial magnetic stimulation has a more significant effect.In terms of improving gait,transcranial direct current stimulation has more advantages.

OBJECTIVE:It has been confirmed that neuromodulation technology can improve the clinical symptoms of patients with Parkinson's disease,and there are differences in the efficacy of different neuromodulation stimulation methods.Herein,a network meta-analysis was used to evaluate the efficacy of different neuromodulation stimulation modalities in improving non-motor symptoms such as sleep disorders and depression and anxiety in patients with Parkinson's disease,thereby exploring the optimal neuromodulation stimulation regimen.METHODS:The Chinese Biomedical Literature Database,WanFang Database,VIP Database,CNKI Database,Web of Science,PubMed,The Cochrane Library,and EMbase databases were searched for randomized controlled trials on neuromodulation techniques to improve sleep disorders,depression and anxiety in patients with Parkinson's disease.The control group was treated with conventional treatments(drugs,conventional rehabilitation therapy,etc.)or sham stimulation,and the experimental group was supplemented with neuromodulation technology on the basis of the control group.The quality of the included studies was evaluated using the PEDro scale and the deviation risk assessment tool recommended by the Cochrane Collaboration.RevMan 5.4 and Stata 17.0 were used for network meta-analysis of the four outcomes(sleep disorders,anxiety symptoms,depressive symptoms,and quality of life).RESULTS:(1)Twenty-nine randomized controlled trials involving six neuromodulation stimulation modalities were included.These modalities were transcranial direct current stimulation,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,deep brain stimulation of the subthalamic nucleus,deep brain stimulation of the globus pallidus,multi-target deep brain stimulation.(2)The results of network meta-analysis showed that compared with conventional treatment,transcranial direct current stimulation[standardized mean difference(SMD)=-2.57,95％confidence interval(CI)=-4.52 to-0.63,P＜0.05)had the best effect in improving sleep disorders in patients with Parkinson's disease.In terms of improving depressive symptoms,deep brain stimulation of the globus pallidus(SMD=-1.00,95％CI=-1.87 to-0.14,P＜0.05)had the best effect,followed by low-frequency repetitive transcranial magnetic stimulation(SMD=-0.91,95％CI=-1.60 to-0.23,P＜0.05),deep brain stimulation of the subthalamic nucleus(SMD=-0.82,95％CI=-1.56 to-0.08,P＜0.05),and high-frequency repetitive transcranial magnetic stimulation(SMD=-0.75,95％CI=-0.97 to-0.53,P＜0.05).In terms of improving anxiety symptoms,high-frequency repetitive transcranial magnetic stimulation(SMD=-0.86,95％CI=-1.54 to-0.18,P＜0.05)had the best effect.In terms of improving the quality of life,deep brain stimulation of the globus pallidus(SMD=-0.79,95％CI=-1.55 to-0.04,P＜0.05)had the best efficacy,followed by high-frequency repetitive transcranial magnetic stimulation(SMD=-0.63,95％CI=-0.90 to-0.36,P＜0.05)and transcranial direct current stimulation(SMD=-0.50,95％CI=-0.80 to-0.19,P＜0.05).CONCLUSION:Neuromodulation technology has significant efficacy in improving non-motor symptoms in patients with Parkinson's disease.Transcranial direct current stimulation has the best efficacy in improving sleep disorders,deep electrical stimulation of the medial cerebral part of the globus pallidus has the best efficacy in improving depressive symptoms,high-frequency repetitive transcranial magnetic stimulation has the best efficacy in improving anxiety symptoms,and deep electrical stimulation of the globus pallidus has the best efficacy in improving quality of life.

OBJECTIVE:Repetitive transcranial magnetic stimulation and transcranial direct current stimulation have shown positive effects in improving gross motor function in children with cerebral palsy.A network meta-analysis was performed to analyze the clinical efficacy of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on the improvement of lower limb motor function and gait in children with cerebral palsy.METHODS:Randomized controlled trials(RCT)about repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor function and gait in children with cerebral palsy were collected from CNKI,WanFang,VIP,SinoMed,PubMed,Web of Science,Medline.The search time limit was from the inception to October 5,2024.After screening literature,extracting data and evaluating the risk of bias of included studies,Stata 15.0 software was used for network meta-analysis,AND GRADE profiler was used for quality evaluation.RESULTS:A total of 19 studies were included,involving 4 treatment measures:conventional therapy,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation and anodic transcranial direct current stimulation.The results of network meta-analysis showed that in terms of improving gross motor function,low-frequency repetitive transcranial magnetic stimulation[mean difference(MD)=9.48,95％confidence interval(CI)(6.61,12.34),P＜0.05]was the most effective.In terms of alleviating spasticity,high-frequency repetitive transcranial magnetic stimulation[MD=-0.63,95％CI(-1.72,0.45),P＜0.05]had the best efficacy.In terms of improving ankle joint range of motion and step speed,transcranial direct current stimulation[MD=2.27,95％CI(1.37,3.17),P＜0.05;MD=0.11,95％CI(0.05,0.17),P＜0.05]was the most effective.CONCLUSION:Existing clinical evidence suggests that low-frequency repetitive transcranial magnetic stimulation has the best therapeutic effect compared with other intervention measures in terms of improving lower limb gross motor function.In terms of reducing spasticity,high-frequency repetitive transcranial magnetic stimulation has a more significant effect.In terms of improving gait,transcranial direct current stimulation has more advantages.

OBJECTIVE:It has been confirmed that neuromodulation technology can improve the clinical symptoms of patients with Parkinson's disease,and there are differences in the efficacy of different neuromodulation stimulation methods.Herein,a network meta-analysis was used to evaluate the efficacy of different neuromodulation stimulation modalities in improving non-motor symptoms such as sleep disorders and depression and anxiety in patients with Parkinson's disease,thereby exploring the optimal neuromodulation stimulation regimen.METHODS:The Chinese Biomedical Literature Database,WanFang Database,VIP Database,CNKI Database,Web of Science,PubMed,The Cochrane Library,and EMbase databases were searched for randomized controlled trials on neuromodulation techniques to improve sleep disorders,depression and anxiety in patients with Parkinson's disease.The control group was treated with conventional treatments(drugs,conventional rehabilitation therapy,etc.)or sham stimulation,and the experimental group was supplemented with neuromodulation technology on the basis of the control group.The quality of the included studies was evaluated using the PEDro scale and the deviation risk assessment tool recommended by the Cochrane Collaboration.RevMan 5.4 and Stata 17.0 were used for network meta-analysis of the four outcomes(sleep disorders,anxiety symptoms,depressive symptoms,and quality of life).RESULTS:(1)Twenty-nine randomized controlled trials involving six neuromodulation stimulation modalities were included.These modalities were transcranial direct current stimulation,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation,deep brain stimulation of the subthalamic nucleus,deep brain stimulation of the globus pallidus,multi-target deep brain stimulation.(2)The results of network meta-analysis showed that compared with conventional treatment,transcranial direct current stimulation[standardized mean difference(SMD)=-2.57,95％confidence interval(CI)=-4.52 to-0.63,P＜0.05)had the best effect in improving sleep disorders in patients with Parkinson's disease.In terms of improving depressive symptoms,deep brain stimulation of the globus pallidus(SMD=-1.00,95％CI=-1.87 to-0.14,P＜0.05)had the best effect,followed by low-frequency repetitive transcranial magnetic stimulation(SMD=-0.91,95％CI=-1.60 to-0.23,P＜0.05),deep brain stimulation of the subthalamic nucleus(SMD=-0.82,95％CI=-1.56 to-0.08,P＜0.05),and high-frequency repetitive transcranial magnetic stimulation(SMD=-0.75,95％CI=-0.97 to-0.53,P＜0.05).In terms of improving anxiety symptoms,high-frequency repetitive transcranial magnetic stimulation(SMD=-0.86,95％CI=-1.54 to-0.18,P＜0.05)had the best effect.In terms of improving the quality of life,deep brain stimulation of the globus pallidus(SMD=-0.79,95％CI=-1.55 to-0.04,P＜0.05)had the best efficacy,followed by high-frequency repetitive transcranial magnetic stimulation(SMD=-0.63,95％CI=-0.90 to-0.36,P＜0.05)and transcranial direct current stimulation(SMD=-0.50,95％CI=-0.80 to-0.19,P＜0.05).CONCLUSION:Neuromodulation technology has significant efficacy in improving non-motor symptoms in patients with Parkinson's disease.Transcranial direct current stimulation has the best efficacy in improving sleep disorders,deep electrical stimulation of the medial cerebral part of the globus pallidus has the best efficacy in improving depressive symptoms,high-frequency repetitive transcranial magnetic stimulation has the best efficacy in improving anxiety symptoms,and deep electrical stimulation of the globus pallidus has the best efficacy in improving quality of life.

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

BACKGROUND: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5. METHODS: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients. RESULTS: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels. CONCLUSIONS A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Cardiovascular Diseases/blood* ; Male ; Female ; Middle Aged ; C-Reactive Protein/metabolism* ; Aged ; Biomarkers/blood* ; Nutrition Surveys ; Adult ; United States/epidemiology* ; Serum Albumin/analysis*

Acute lung injury (ALI) has been a kind of acute and severe disease that is mainly characterized by systemic uncontrolled inflammatory response to the production of huge amounts of reactive oxygen species (ROS) in the lung tissue. Given the critical role of ROS in ALI, a Fe₃O₄ loaded bovine serum albumin (BSA) nanocluster (BF) was developed to act as a nanomedicine for the treatment of ALI. Combining with NIR irradiation, it exhibited excellent ROS scavenging capacity. Significantly, it also displayed the excellent antioxidant and anti-inflammatory functions for lipopolysaccharides (LPS) induced macrophages (RAW264.7), and Sprague Dawley rats via lowering intracellular ROS levels, reducing inflammatory factors expression levels, inducing macrophage M2 polarization, inhibiting NF-κB signaling pathway, increasing CD4⁺/CD8⁺ T cell ratios, as well as upregulating HSP70 and CD31 expression levels to reprogram redox homeostasis, reduce systemic inflammation, activate immunoregulation, and accelerate lung tissue repair, finally achieving the synergistic enhancement of ALI immunotherapy. It finally provides an effective therapeutic strategy of BF + NIR for the management of inflammation related diseases.

Objective To analyze the current status of knowledge,attitude,and behavior?(KAP)of doctors and pharmacists regarding iodine contrast agent allergic reactions in medical institutions in China and the influencing factors,to provide reference for the treatment of iodine contrast agent allergic patients.Methods A questionnaire survey on iodine contrast agent allergic reactions was conducted among doctors and pharmacists in China using a self-designed questionnaire.The questionnaire was distributed online via WeChat and the participants were anonymous and voluntary.The scores of knowledge,attitude,and behavior of medical staff of different genders,departments,and titles were statistically analyzed.Wilcoxon rank sum test and multiple linear regression analysis were used to analyze the influencing factors.Results A total of 105 doctors and pharmacists from 19 provinces,autonomous regions and municipalities participated in the survey,completing 105 valid questionnaires.The knowledge score(out of 4 points),attitude score(out of 3 points),and behavior score(out of 3 points)of doctors and pharmacists regarding contrast agent allergy reactions were 2(1,2)points,1(0,2)points,and 1(1,2)points,respectively.Multivariate linear regression analysis showed that job title is a factor affecting the knowledge score.Compared to those with primary and below titles,senior title doctors and pharmacists had higher knowledge scores(P=0.007).Educational level is a influence factor affecting the attitude score.Compared to those with undergraduate and below educational levels,doctors and pharmacists with doctoral degrees had more positive attitudes(P=0.011).Attitude score is a influence factor affecting the behavior score,the more positive the attitude,the more positive the behavior(P=0.015).Conclusion The knowledge,attitude,and practice(KAP)of doctors and pharmacists regarding contrast agent allergy reactions need to be strengthened.Training should be conducted for doctors and pharmacists,taking into account the KAP differences among individuals with different job titles and educational levels,to enhance knowledge levels and actively explore safe and effective desensitization treatment methods for patients with contrast agent allergies.The use of iodinated contrast agents should be rationalized while ensuring patient safety.

BACKGROUND:Peripheral nerve injuries can cause severe functional disabilities in patients,and long-segment nerve defects often fail to regenerate spontaneously.In recent years,tissue engineering techniques have gradually been applied to the repair of long-segment nerve injuries,yet research hotspots and development trends are unclear.OBJECTIVE:To analyze the research hotspots and trends in the field of peripheral nerve tissue engineering over the past 20 years using bibliometric software.METHODS:CiteSpace 6.2R6 software was employed to conduct highly cited analysis and keyword analysis on peripheral nerve tissue engineering literature published from 2004 to 2024 in the Web of Science and China National Knowledge Infrastructure(CNKI)databases.The keyword analysis encompasses keyword co-occurrence analysis,keyword clustering analysis,keyword timeline analysis,and keyword emergence analysis.RESULTS AND CONCLUSION:A total of 2 961 articles from the Web of Science database and 1171 articles from the CNKI database were included.The number of publications in the Web of Science database showed fluctuations but exhibited an overall increasing trend year by year,while the publication volume in the CNKI database remained relatively stable annually.Most of the top ten most cited articles in the Web of Science database were review articles.The results of the keyword analysis from Web of Science and CNKI databases indicated that the most studied nerve tissue engineering materials over the past 20 years include silk fibroin,collagen,chitosan,polycaprolactone,polylactic acid,and graphene.The biochemical cues investigated in these materials include olfactory ensheathing cells,Schwann cells,stem cells,and nerve growth factors.The most commonly employed external physical factor is electrical stimulation applied to the materials.Among various tissue engineering techniques,electrospinning technology and 3D printing technology have been the most extensively researched.

BACKGROUND:Cervical disc degeneration is a common degenerative disease,and inflammatory proteins play an important role in cervical disc degeneration,but the specific mechanisms involved remain to be thoroughly investigated.OBJECTIVE:Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration.METHODS:Genome-wide association analysis statistics for 91 inflammatory proteins(from GCST90274758 to GCST90274848)were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database(finngen_R10_M13_CERVICDISCV).Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration.Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable,and then the inverse Mendelian randomization analysis was performed in the same way.RESULTS AND CONCLUSION:The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration,of which glial cell lineage-derived neurotrophic factor(odds ratio(OR)=1.095,95%confidence interval(CI):1.012-1.184,P=0.023),interleukin 4(OR=1.094,95%CI:1.002-1.194,P=0.045)and monocyte chemotactic protein-1 levels(OR=1.062,95%CI:1.001-1.127,P=0.048)showed a direct positive causal association with the risk of cervical disc degeneration;interleukin 17C(OR=0.906,95%CI:0.839-0.979,P=0.013),interleukin 18(OR=0.924,95%CI:0.866-0.986,P=0.017)and interleukin 2 levels(OR=0.894,95%CI:0.821-0.973,P=0.010)showed a direct negative causal association with the risk of cervical disc degeneration.The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data,there was no significant causal relationship with any of the 91 inflammatory proteins.The results of the sensitivity analysis showed that the Cochran's Q test for the two-way Mendelian randomization,the MR-Egger regression method,and the MR-PRESSO results had P values greater than 0.05,indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration.To conclude,there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor,interleukin 4,monocyte chemotactic protein-1,interleukin 17C levels,interleukin 18,and interleukin 2 levels and cervical disc degeneration,which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration.