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 assess the fall risk of hospitalized patients with cardiovascular diseases, analyze the related influencing factors, and construct a prediction model based on machine learning technology, so as to provide a basis for the fall management of hospitalized patients with cardiovascular diseases.Methods:This study was a retrospective cohort study. A total of 450 patients admitted to the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University from June 2017 to June 2024 were selected as the research objects by convenience sampling method. By reviewing electronic medical records, trained nurses extracted the patients' general information and Activities of Daily Living Scale (ADL) scores during hospitalization. Lasso regression was used to screen risk factors, and machine learning libraries were used to construct support vector machine (SVM), decision tree, XGBoost, and neural network models. Bootstrap resampling method and area under the curve (AUC) were used to verify the model performance.Results:Among the 450 patients, there were 261 males and 189 females, with a mean age of (66.0 ± 8.4) years. Among them, 90 patients fell during hospitalization and 360 patients did not fall. The results of Lasso regression showed that ADL score ≤60 points, use of hypnotics, hypokalemia, nighttime toilet visits≥2 times, use of antihypertensive drugs, no caregiver, and history of atrial fibrillation were all risk factors for falls in hospitalized patients with cardiovascular diseases (regression coefficients ranging from 0.61 to 1.20, all P<0.01). Among the machine learning models, XGBoost had the best comprehensive performance (AUC=0.98), which was better than decision tree (AUC=0.66), SVM (AUC=0.95), and neural network (AUC=0.87). Conclusions:The fall risk of hospitalized patients with cardiovascular diseases is jointly affected by physiological, medication and behavioral factors, and the XGBoost model can effectively identify high-risk groups. In actual clinical work, nursing strategies can be optimized in combination with risk factors, and the application of intelligent fall prediction and assessment tools can be promoted.

Mastitis is one of the common and prevalent diseases in dairy cows,and the natural prod-uct daidzein is a kind of natural flavonoids with a wide range of pharmacological and anti-inflam-matory effects.However,the effect of daidzein on mastitis in dairy cows has not been reported.Therefore,in this study,we explored the effects of daidzein on LPS-induced inflammatory response and tight junction damage in dairy mammary epithelial cells Firstly,we pretreated the MAC-T cell line using different concentrations of daidzein,and it was clarified that daidzein below 200 μmol/L had no effect on the cell activity.Next,we examined the production of pro-inflammatory mediators in LPS-stimulated MAC-T cell lines using qRT-PCR,and clarified that daidzein could reduce the production of pro-inflammatory mediators in a concentration-dependent manner.Subsequently,af-ter the expression of Occludin,Claudin3 and ZO-1 was detected by immunofluorescence and West-ern Blot,it was clear that daidzein could alleviate MAC-T cell intercellular tight junction injury.Fi-nally,it was demonstrated that daidzein significantly inhibited LPS-induced activation of the NF-κB signaling pathway within MAC-T using network pharmacological analysis and Western Blot.The above results suggest that daidzein can inhibit LPS-induced inflammatory response and tight junc-tion damage in mammary epithelial cells of cows by suppressing the activation of NF-κB signaling pathway.The present study provides a theoretical basis for the alleviation of mastitis by natural products and further expands the pharmacological effects of daidzein.

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.

With the continuous development of refractive surgery, people's focus has gradually shifted from improving vision to improving visual quality, and personalized laser-assisted in situ keratomileusis(LASIK)surgery has gradually become people's preferred choice. Femtosecond laser-assisted keratoplasty provides better advantages for personalized LASIK surgery. This article mainly introduces the commonly used femtosecond laser-assisted personalized LASIK surgery(FS-LASIK)in recent years, such as wavefront-optimized, wavefront-guided, topography-guided, Q value-guided(aspheric cutting), personalized surgery “Wavelight Plus” and personalized surgery when correcting patients with age-related inadequate accommodation. This article focuses on analyzing the advantages and disadvantages of different personalized FS-LASIK, as well as the research progress in recent years, and also focuses on comparing the differences between different personalized surgeries.