Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Non-steroidal anti-inflammatory drugs(NSAIDs),commonly utilized analgesics,are extensively employed for managing pain associated with musculoskeletal disorders or injuries.Recent clinical studies have demonstrated a heightened risk of bone stress injuries(BSI)in soldiers and athletes,particularly during high-intensity training,due to NSAID usage.Furthermore,the impact of NSAIDs on fracture healing is well-documented;however,the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear.This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs,optimize pain management strategies,and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.

Objective To explore the pathogenesis of Alzheimer's disease by examining the effects of dihydroartemisinin(DHA)on cognitive behavior,hippocampal,cerebral cortex and retinal cell morphology,β-amyloid(Aβ)and autophagy-related proteins in 5×FAD mice.Methods Twenty 5×FAD mice and 5 wild type(WT)mice were selected,all of which were female.The 5×FAD mice were randomly divided into model(M)group,donepezil(D)group,low-dose DHA(DHA-L)group,and high-dose DHA(DHA-H)group.The WT and M groups were not treated,and the D group was given donepezil 0.1 mg/kg per day.DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day,respectively.Group D,group DHA-L and group DHA-H were given intragastric administration once a day for 3 months.The changes of in cognitive behavior were measured by Morris experiment.HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex,hippocampus and retina.The expressions of Aβ protein in cerebral cortex,hippocampus and retina were detected by immunohistochemistry.Western blotting detected the expression of autophagy related proteins(LC3-Ⅰ,LC3-Ⅱ,Beclin-1,P62,β-actin).Results The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes.Compared to the model group,significant differences in the contents of Aβ in the hippocampal CA1,cerebral cortex S1,and retinal were observed(P＜0.0001)in the other four groups.The analysis also showed significant differences in autophagy-associated proteins between the DHA-L,DHA-H,and model groups(P＜0.01).Conclusion DHA improves cognitive function and increases the number of nerve cells in mice.It also reduces Aβ content in the cerebral cortex,hippocampus,and retina,along with improving autophagy-associated protein deposition in mice.

Objective To summarize the clinical and genetic characteristics of end-stage renal disease caused by PLCE1 gene mutations.Methods A retrospective analysis of the clinical and genetic features of three children from a family with PLCE1 gene mutations was conducted,along with a literature review of hereditary kidney disease cases caused by PLCE1 gene mutations.Results The proband was an 8-year-old male presenting with nephrotic syndrome stage 4 chronic kidney disease.Renal biopsy showed focal segmental glomerulosclerosis.Two years and five months after kidney transplantation,the patient had persistent negative proteinuria and normal renal function.Whole-exome sequencing identified two pathogenic heterozygous variants:c.961C>T and c.3255_3256delinsT,with c.3255_3256delinsT being a novel mutation.Family screening revealed no renal involvement in the parents,but among five siblings,one brother died at age of 4 years from end-stage renal disease.A 7-year-old sister presented with proteinuria and bilateral medullary sponge kidney,with proteinuria resolving after one year of follow-up.A 3-year-old brother died after kidney transplantation due to severe pneumonia.The literature review included 45 patients with hereditary kidney disease caused by PLCE1 gene mutations.The main clinical phenotype was nephrotic syndrome(87%,39/45),and renal pathology predominantly showed focal segmental glomerulosclerosis(57%,16/28).No mutation hotspots were identified.Conclusions Compound heterozygous mutations in the PLCE1 gene can lead to rapid progression of the disease to end-stage renal disease,with favorable outcomes following kidney transplantation.Family screening is crucial for early diagnosis,and medullary sponge kidney may be a novel phenotype associated with these gene mutations.Citaion:[Chinese Journal of Contemporary Pediatrics,2025,27(5):580-587]

AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

OBJECTIVES: To study the clinical characteristics, efficacy, and prognosis of pediatric Langerhans cell histiocytosis (LCH). METHODS: A retrospective analysis was conducted on 72 children with newly diagnosed LCH. RESULTS: The median age of the 72 children was 5 years (range: 0-14 years), with skull involvement being the most common (56 cases, 77.8%). The BRAF-V600E mutation was not associated with clinical characteristics, efficacy, or prognosis (P>0.05). The 5-year overall survival rate was 91.6%±4.2%, and the 5-year event-free survival (EFS) rate was 67.5%±5.8%. The 6-week chemotherapy response rate and 5-year EFS rate were lower in the risk organ involvement group compared to the no risk organ involvement group (P<0.05). The five-year overall survival rates for the group with multi-system involvement and the group with platelet count ≥450×10⁹/L were respectively lower than those for the single-system involvement group and the group with platelet count <450×10⁹/L (P<0.05). Risk organ involvement is an independent risk factor for 5-year EFS (P<0.05). CONCLUSIONS Skull is the most commonly affected site in pediatric LCH. The BRAF-V600E mutation is not related to clinical characteristics, efficacy, or prognosis. Elevated platelet count, risk organ involvement, and multisystem involvement are associated with poor prognosis, with risk organ involvement being an independent risk factor for 5-year EFS.
Humans ; Histiocytosis, Langerhans-Cell/therapy* ; Child, Preschool ; Child ; Male ; Infant ; Female ; Adolescent ; Retrospective Studies ; Proto-Oncogene Proteins B-raf/genetics* ; Prognosis ; Infant, Newborn ; Mutation

OBJECTIVES: To summarize the clinical and genetic characteristics of end-stage renal disease caused by PLCE1 gene mutations. METHODS: A retrospective analysis of the clinical and genetic features of three children from a family with PLCE1 gene mutations was conducted, along with a literature review of hereditary kidney disease cases caused by PLCE1 gene mutations. RESULTS: The proband was an 8-year-old male presenting with nephrotic syndrome stage 4 chronic kidney disease. Renal biopsy showed focal segmental glomerulosclerosis. Two years and five months after kidney transplantation, the patient had persistent negative proteinuria and normal renal function. Whole-exome sequencing identified two pathogenic heterozygous variants: c.961C>T and c.3255_3256delinsT, with c.3255_3256delinsT being a novel mutation. Family screening revealed no renal involvement in the parents, but among five siblings, one brother died at age of 4 years from end-stage renal disease. A 7-year-old sister presented with proteinuria and bilateral medullary sponge kidney, with proteinuria resolving after one year of follow-up. A 3-year-old brother died after kidney transplantation due to severe pneumonia. The literature review included 45 patients with hereditary kidney disease caused by PLCE1 gene mutations. The main clinical phenotype was nephrotic syndrome (87%, 39/45), and renal pathology predominantly showed focal segmental glomerulosclerosis (57%, 16/28). No mutation hotspots were identified. CONCLUSIONS Compound heterozygous mutations in the PLCE1 gene can lead to rapid progression of the disease to end-stage renal disease, with favorable outcomes following kidney transplantation. Family screening is crucial for early diagnosis, and medullary sponge kidney may be a novel phenotype associated with these gene mutations.
Humans ; Male ; Proteinuria/genetics* ; Kidney Failure, Chronic/etiology* ; Child ; Mutation ; Female ; Child, Preschool ; Retrospective Studies ; Phosphoinositide Phospholipase C