BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.

Tumors are the second leading cause of death worldwide. Exosomes are a type of extracellular vesicle secreted from multivesicular bodies, with particle sizes ranging from 40 to 160 nm. They regulate the tumor microenvironment, proliferation, and progression by transporting proteins, nucleic acids, and other biomolecules. Compared with other drug delivery systems, exosomes derived from different cells possess unique cellular tropism, enabling them to selectively target specific tissues and organs. This homing ability allows them to cross biological barriers that are otherwise difficult for conventional drug delivery systems to penetrate. Due to their biocompatibility and unique biological properties, exosomes can serve as drug delivery systems capable of loading various anti-tumor drugs. They can traverse biological barriers, evade immune responses, and specifically target tumor tissues, making them ideal carriers for anti-tumor therapeutics. This article systematically summarizes the methods for exosome isolation, including ultracentrifugation, ultrafiltration, size-exclusion chromatography (SEC), immunoaffinity capture, and microfluidics. However, these methods have certain limitations. A combination of multiple isolation techniques can improve isolation efficiency. For instance, combining ultrafiltration with SEC can achieve both high purity and high yield while reducing processing time. Exosome drug loading methods can be classified into post-loading and pre-loading approaches. Pre-loading is further categorized into active and passive loading. Active loading methods, including electroporation, sonication, extrusion, and freeze-thaw cycles, involve physical or chemical disruption of the exosome membrane to facilitate drug encapsulation. Passive loading relies on drug concentration gradients or hydrophobic interactions between drugs and exosomes for encapsulation. Pre-loading strategies also include genetic engineering and co-incubation methods. Additionally, we review approaches to enhance the targeting, retention, and permeability of exosomes. Genetic engineering and chemical modifications can improve their tumor-targeting capabilities. Magnetic fields can also be employed to promote the accumulation of exosomes at tumor sites. Retention time can be prolonged by inhibiting monocyte-mediated clearance or by combining exosomes with hydrogels. Engineered exosomes can also reshape the tumor microenvironment to enhance permeability. This review further discusses the current applications of exosomes in delivering various anti-tumor drugs. Specifically, exosomes can encapsulate chemotherapeutic agents such as paclitaxel to reduce side effects and increase drug concentration within tumor tissues. For instance, exosomes loaded with doxorubicin can mitigate cardiotoxicity and minimize adverse effects on healthy tissues. Furthermore, exosomes can encapsulate proteins to enhance protein stability and bioavailability or carry immunogenic cell death inducers for tumor vaccines. In addition to these applications, exosomes can deliver nucleic acids such as siRNA and miRNA to regulate gene expression, inhibit tumor proliferation, and suppress invasion. Beyond their therapeutic applications, exosomes also serve as tumor biomarkers for early cancer diagnosis. The detection of exosomal miRNA can improve the sensitivity and specificity of diagnosing prostate and pancreatic cancers. Despite their promising potential as drug delivery systems, challenges remain in the standardization and large-scale production of exosomes. This article explores the future development of engineered exosomes for targeted tumor therapy. Plant-derived exosomes hold potential due to their superior biocompatibility, lower toxicity, and abundant availability. Furthermore, the integration of exosomes with artificial intelligence may offer novel applications in diagnostics, therapeutics, and personalized medicine.

AIM: To investigate the relationship between the levels of serum dehydroepiandrosterone(DHEA), erythropoietin(Epo), vasohibin-1(VASH-1)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM). METHODS: Totally 185 T2DM patients(185 eyes)treated in our hospital from April 2021 to March 2024 were selected and divided into T2DM group(102 eyes)and DR group(83 eyes)based on whether retinal lesions occurred. DR patients were divided into nonproliferative DR group(NPDR, 47 cases, 47 eyes)and proliferative DR group(PDR, 36 cases, 36 eyes)based on the severity of their lesions. Fully automatic biochemical analyzer was used to detect serum biochemical indicators. ELISA was applied to detect serum levels of DHEA, Epo, and VASH-1. Pearson correlation was applied to analyze the correlation between serum DHEA, Epo, and VASH-1 levels and the severity of diabetic retinopathy. Logistic regression was applied to analyze the factors affecting the occurrence of DR. ROC curve was applied to analyze the diagnostic value of serum DHEA, Epo, and VASH-1 levels for T2DM combined with DR or PDR.RESULTS: Compared with the T2DM group, the DR group showed significantly increased DM duration, fasting blood glucose, uric acid, creatinine, and Epo, while DHEA and VASH-1 levels were significantly reduced(all P<0.05); Compared with the NPDR group, the PDR group showed a significant decrease in serum DHEA and VASH-1 levels, and a significant increase in Epo levels(all P<0.05); the levels of serum DHEA and VASH-1 were negatively correlated with the severity of DR, while the level of Epo was positively correlated with the severity of DR(all P<0.05); DHEA and VASH-1 were protective factors against DR, while Epo was a risk factor for DR(all P<0.05); the AUC of serum DHEA, Epo, and VASH-1 levels alone and in combination for the diagnosis of T2DM with DR were 0.804, 0.797, 0.805, and 0.903, respectively. The combined diagnostic value was higher than that of single diagnosis(all P<0.05); the AUC of serum DHEA, Epo, and VASH-1 levels alone and in combination for diagnosing PDR were 0.852, 0.850, 0.841, and 0.946, respectively. The value of combined diagnosis was significantly higher than that of individual diagnosis(all P<0.05).CONCLUSION:The levels of serum DHEA and VASH-1 in DR patients are clearly reduced, the level of Epo is clearly increased, and their levels are closely related to the severity of DR patients; therefore, combined detection has higher value for T2DM complicated with DR or PDR.

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

Dysfunction of drug transporters significantly affects therapeutic outcomes and drug efficacy in patients with liver injury. Clinical and experimental evidence demonstrates that liver injury involves complex inter-organ interactions among the brain, eye, liver, intestine, and kidney. Recent advances in basic and clinical research have illuminated the physiologic and molecular mechanisms underlying transporter alterations in liver injury, particularly those associated with bilirubin, reactive oxygen species, ammonia, bile acid, and inflammatory factors. Notably, the influence of these transporter modifications on drug pharmacokinetics in liver injury patients remains inadequately understood. Additional research is necessary to fully comprehend these effects and their therapeutic implications. The documented alterations of transporters in distant organs across various liver diseases indicate that dosage modifications may be required when administering transporter-substrate drugs, including both traditional Chinese and Western medicines, to patients with liver dysfunction. This strategy helps maintain drug concentrations within therapeutic ranges while reducing adverse reactions. Furthermore, when utilizing transporter inducers or inhibitors clinically, consideration of their long-term effects on transporters and subsequent therapeutic impact is essential. Careful attention must be paid to avoid compromising the elimination of toxic metabolites and proteins when inhibiting these transporters. Similarly, prudent use of inducers or inducer-type therapeutic drugs is necessary to prevent enhanced drug resistance. This review examines recent clinical and experimental findings regarding the inter-organ interaction of drug transporters in liver injury conditions and their clinical relevance.
Humans ; Liver/drug effects* ; Animals ; Chemical and Drug Induced Liver Injury/metabolism* ; Membrane Transport Proteins/metabolism* ; Biological Transport ; Liver Diseases/drug therapy* ; Pharmaceutical Preparations/metabolism*

Occupational pneumoconiosis remains the most common occupational disease in China, with occupational mineral dust exposure being its primary causative factor. Although national standards for online monitoring and early warning systems of coal mine dust concentrations have been established, national occupational health standards for rapid and online monitoring of dust concentration and particle size distribution in other industries are still limited. Among dust concentration sensor technologies, the light scattering method is the preferred choice for online dust monitoring owing to its wide measurement range and low cost. The beta-ray absorption method is mature but highly sensitive to humidity. The electrostatic induction method offers high sensitivity, simple structure, and low maintenance costs but exhibits high errors in low-concentration dust monitoring. The tapered element oscillating microbalance method is highly sensitive but costly. Multi-sensor data fusion technology can improve monitoring reliability, however, mature domestic products are not yet available. For monitoring dust particle size distribution, sieving and sedimentation methods are cumbersome. The aerodynamic method shows broad prospects in the online monitoring of respirable dust but has obvious measurement errors for larger dust particles. The use of optical measurement method is limited by dust morphology and is not suitable for monitoring coal dust particle size distribution. The electrical mobility method is primarily applicable to submicron dust. Future research should focus on promoting the application of monitoring technology for respirable dust particle size distribution in online monitoring of industrial dust. By integrating Internet of Things, data mining, and artificial intelligence technologies, along with multi-sensor data fusion and numerical simulation, dust concentration prediction models can be established to achieve accurate dust concentration monitoring and early warning of exceedances. The advancements of technologies will provide scientific support for the assessment of industrial dust hazards and the prevention and control of occupational pneumoconiosis.

Objective:To investigate the effect of Chinese Herbal Anti-Alopecia and Hair Growth Solution(CHAaHGS)on the hair growth through in vitro experiments on the human dermal papilla cells(HDPCs),in vivo experiments in the C57BL/6 mice,and human efficacy tests,and to clarify its potential mechanism.Methods:The HDPCs were divided into control group,CHAaHGS group,and minoxidil group.MTT method was used to detect the proliferation activities of HDPCs in various groups;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of vascular endothelial growth factor(VEGF),hepatocyte growth factor(HGF),insulin-like growth factor-1(IGF-1),and transforming growth factor β1(TGF-β1)in the supernatant of HDPCs in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of VEGF,HGF,IGF-1,TGF-β1,and alkaline phosphatase(ALP)mRNA in the HDPCs in various groups;Western blotting method was used to detect the expression levels of β-catenin,dishevelled segment polarity protein 1(DVL1),glycogen synthase kinase 3β(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),and wingless-type MMTV integration site family member 3a(Wnt3a)proteins in the HDPCs in various groups.A total of 18 mice were randomly divided into control group,CHAaHGS group,and minoxidil group,with 6 mice in each group.The mouse hair loss model was established using hair removal cream,and corresponding drug treatments were administered immediately after hair removal.The lengths and weights of newly grown hair on day 21 of the mice in various groups were detected;HE staining was used to observe the morphology of hair follicles in the dorsal depilated skin areas of the mice in various groups on day 7;ELISA method was used to detect the levels of VEGF,HGF,IGF-1,and TGF-β1 in the skin tissue of dorsal depilated areas of the mice in various groups.Sixty subjects were randomly divided into control group and CHAaHGS group,with 30 subjects in each group.The numbers of hair loss and hair densities of the subjects in various groups were detected at weeks 0,4,8,and 12.Results:The MTT assay results showed that compared with control group,the proliferation activity of the cells in 50 mg·L-1CHAaHGS group was significantly increased(P＜0.01).The ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in the cell supernatant of HDPCs in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.01).The RT-qPCR results showed that compared with control group,the expression levels of VEGF,HGF,IGF-1,and ALP mRNA in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 mRNA expression level was significantly decreased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of β-catenin,DVL1,p-GSK-3βand Wnt3a proteins in the cells in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the GSK-3β protein expression level was significantly decreased(P＜0.05).In animal experiments,on day 21,compared with control group,the length of newly grown hair of the mice in CHAaHGS group was significantly increased(P＜0.05),and the hair weight was significantly increased(P＜0.01).On day 7,the HE staining results showed that compared with control group,the hair follicle spacing of the mice in CHAaHGS group was significantly decreased(P＜0.05),and the number of hair follicles was significantly increased(P＜0.01);the ELISA assay results showed that compared with control group,the levels of VEGF,HGF,and IGF-1 in skin tissue of dorsal depilated area of the mice in CHAaHGS group were significantly increased(P＜0.05 or P＜0.01),and the TGF-β1 level was significantly decreased(P＜0.05).In human efficacy test,compared with control group,the number of hair loss of the subjects in CHAaHGS group was significantly decreased at week 12(P＜0.01),and the local hair density was increased(P＜0.05).Conclusion:CHAaHGS promotes hair growth,and the mechanism may be related to its ability to increase the proliferation activity of HDPCs,induce the secretion of VEGF,HGF,and IGF-1,and activate the Wnt/β-catenin signaling pathway.

In analytical techniques such as ion mobility spectrometry(IMS)and mass spectrometry(MS),the ionization efficiency of target analytes is primarily constrained by the type of ionization source and factors such as the species and number density of the reactant ions.Systematic investigation into the reactivity differences of various reactant ions under varying conditions can not only significantly enhance the detection sensitivity of target compound product ions but also provide a theoretical foundation for establishing efficient detection methods based on ion-molecule reaction mechanisms.In this study,the pressure of a pressure-tunable photoionization tandem ion mobility spectrometry(PI-tandem-IMS)was reduced from ambient pressure(100 kPa)to low pressure(20 kPa)to systematically examine the reactivity differences between two negative reactant ions,CO3-and CO4-,and methyl salicylate(MeSA)under varying pressures.When the pressure decreased,the increased relative signal intensity of CO4-significantly influenced the detection sensitivity of the characteristic product ion[MeSA·O2]-.Based on differences in ion mobility(k0),the delay time for the opening of TPG2 was adjusted to selectively inject CO-3 and CO-4 in the drift region 2.Independent characterization of the reactivity of these reactant ions with MeSA in the reaction region confirmed that CO4-exhibited superior reactivity toward MeSA.The theoretical model revealed an Arrhenius plot for the ion-molecule reaction between CO4-and MeSA,showing a positive correlation between the reaction rate coefficient(k)and temperature,the activation energy Ea was 62.45 kJ/mol.Furthermore,controlling parameters such as pressure or temperature significantly influenced the progression of this ion-molecule reaction,demonstrating the technical advantages of PI-tandem-IMS in mechanistic studies and regulation of ion-molecule reactions.

The resolving power and sensitivity are critical for on-site detection of hazardous chemicals using stand-alone ion mobility spectrometry(IMS).However,improving the sensitivity and resolving power of IMS has long been a prominent research hot spot.In the commonly used IMS based on the Bradbury-Nielsen gate(BNG),the gating voltage difference(GVD)applied between the two sets of grid wires affects the electric field distribution in the ionization region and the drift region.This,in turn,influences the spatial distribution and temporal width of the injected ion swarm,and has an impact on the ion mobility discrimination,sensitivity,and resolving power of the instrument.This study showed that increasing the GVD could induce an ion converging effect,boosting the ion number density in front of the BNG by nearly 300％.To simultaneously utilize temporal compression and ion converging effects,a novel BNG controlling mode was proposed by adding a chopping state to the conventional controlling mode.This chopping state reduced the mobility discrimination effects between ions with mobility differences up to about 0.90 cm2/(V·s)to 1/22 of their original value.When analyzing hazardous chemical mixtures using the novel BNG controlling mode,compared with conventional mode,the signal intensity of low-mobility methyl salicylate ions(MS·O2)-increased by 18-fold while the resolving power maintained around 100,and the detection limit for MS was improved from 3.75 &mu;g/L to 97 ng/L.This novel BNG controlling mode only added a potential wave to the low voltage wires,with no requirement of changing the structure of the drift tube,and was easy to apply to existing commercial instruments.

Objectives:To develop modified prehospital stroke scales and to evaluate their predictive value for in-hospital acute large vessel occlusion (LVO) stroke.Methods:Patients admitted to Dongtai People's Hospital due to non-stroke-related diseases and activated the in-hospital stroke green channel due to suspected stroke symptoms during hospitalization from January 2015 to December 2022 were included retrospectively. According to the final imaging diagnosis, they were divided into LVO group and non-LVO group. The five prehospital stroke scales included Field Assessment Stroke Triage for Emergency Destination (FAST-ED), Rapid Arterial Occlusion Evaluation (RACE), Los Angeles Motor Scale (LAMS), Cincinnati Prehospital Stroke Severity Scale (CPSSS), and Prehospital Acute Stroke Severity Scale (PASS). Multivariate logistic regression analysis was used to determine independent predictive factors of LVO in patients with in-hospital stroke, and incorporating them into the prehospital stroke scale to develop modified scales. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the modified scales. Results:A total of 174 patients with in-hospital stroke were enrolled, including 92 males (52.9%), aged 65.7±11.9 years. Fifty-four patients (31.0%) had LVO, and 59 (33.9%) had a surgical history within 3 days before the onset of stroke, mainly cardiopulmonary surgeries. Multivariate logistic regression analysis showed that atrial fibrillation (odds ratio 2.940, 95% confidence interval 1.387-6.230; P=0.005) and recent history of cardiopulmonary surgery (odds ratio 6.861, 95% confidence interval 2.437-11.315; P<0.001) were the independent predictive factors of LVO in patients with in-hospital stroke. According to the β coefficient and ROC curve, they were assigned a score of 1 and included in the prehospital stroke scale. The area under the curve of the modified scale for predicting LVO (mRACE: 0.917; mFAST-ED: 0.865; mPASS: 0.859; mCPSSS: 0.853; mLAMS: 0.907) was significantly higher than the corresponding original scale (RACE: 0.888; FAST-ED: 0.820; PASS: 0.786; CPSSS: 0.810; LAMS: 0.859) (all P<0.05). Conclusion:The modified scales based on the prehospital stroke scales can significantly improve the predictive value of in-hospital acute LVO stroke compared to the original prehospital stroke scales.