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.

Compared with conventional transdermal drug delivery systems, dissolving microneedles significantly enhance drug bioavailability by penetrating the stratum corneum barrier and achieving intradermal drug delivery. In order to improve the transdermal bioavailability of dexmedetomidine hydrochloride, in this study, a novel microneedle delivery system was developed for dexmedetomidine hydrochloride based on 3D printing combined with micro-molding. By systematically optimizing the microneedle geometrical parameters, array arrangement, and preparation process parameters, we determined the optimal ratio of drug-carrying matrix as 15% PVP (polyvinyl pyrrolidone) K90. The microneedles exhibited significant drug loading gradients, with mean content of (209.99±27.56) μg/patch, (405.31±30.31) μg/patch, and (621.61±34.43) μg/patch. They showed a regular pyramidal structure under SEM and handheld electron microscopy, and their mechanical strength allowed effective penetration into the stratum corneum. The surface contact angles were all < 90°, indicating excellent hydrophilicity. The microneedles dissolved completely within 10 min after skin insertion, achieving a cumulative release rate of 90% (Higuchi model, r=0.996) during 2 hours of in vitro transdermal permeation. The cytotoxicity test and hemolysis test verified good biocompatibility. Pharmacodynamic evaluation showed that the microneedle group demonstrated pain-relieving effect within 15 min, with the pain threshold at the time point of 60 min being 3 times that in the transdermal cream group. The microneedle system developed in this study not only offers an efficient drug delivery option for patients but also establishes an innovative platform for rapid percutaneous delivery of hydrophilic drugs, demonstrating significant potential in perioperative pain management.
Dexmedetomidine/pharmacokinetics* ; Printing, Three-Dimensional ; Needles ; Drug Delivery Systems/methods* ; Administration, Cutaneous ; Animals ; Microinjections/instrumentation* ; Skin Absorption ; Skin/metabolism*

Objective : To investigate the effects of cinnamaldehyde(CA) on the growth, metastasis and apoptosis of human endometriosis(EMs) cells and to explore whether the mechanism is related to ribosomal protein S7(RPS7) expression. Methods : Endometriosis cells were divided into control group, CA group, sh-NC group, CA+sh-RPS7 group. Effects of CA on cell growth in human endometriotic cells were determined using Cell Counting Kit-8(CCK-8) and colony formation assay. Effects of CA on cell metastasis were performed by motility assay and Transwell assay. Effects of CA on cell apoptosis were evaluated by Hoechst 33258 staining and flow cytometry. Meanwhile, the levels of PCNA, E-cadherin, Vimentin, Bax and Bcl-2 were evaluated using Western blot in human endometriotic cells with treatment CA. The expression of RPS7 was detected by qRT-PCR and Western blot assay. The RPS7 overexpression of human endometriotic cells was established by cell transfection. CA-mediated effects on cell proliferation and apoptosis were determined by CCK-8 assay and flow cytometry in human endometriotic cells with RPS7 overexpression. Results : CA repressed cell growth as well as down-regulated PCNA. The half inhibitory concentration(IC50) value was 53.60 μmol/L after 24 h treatment, and colony formation rate was 25.32%. Additionally, CA inhibited metastasis which was associated with downregulated Vimentin and upregulated E-cadherin. The relative migration rates were 35% and 29% as well as invasion rate was 40%. Further, CA induced apoptosis by cell cycle G2/M phase arrest and cell apoptosis rate was 25.1%, which related to the up-regulation of of Bax and the down-regulation of Bcl-2. CA inhibited the expression of RPS7 and overexpression of RPS7 promoted cell proliferation and suppressed apoptosis in CA-mediated cells. Conclusion CA inhibits cell growth, metastasis, and induces cell apoptosis by downregulating the expression of RPS7.

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.

To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine， and its core pathogenesis is center fullness with internal heat， while obesity is the initiating factor for exacerbating center fullness and internal heat， therefore， it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight， obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao， with qi depression as the root and turbidity obstruction as the cause， forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic， Dahuang Huanglian Xiexin Decoction （大黄黄连泻心汤） is used as the basic prescription， with a primary focus on directing the turbid downward， supplemented by regulating qi， which embodies the concept of "promoting movement through descent， then figuring out the root of spleen-heat syndrome. Furthermore， the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.