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.

Cell models can simulate a variety of life states and disease developments, including single cells, two-dimensional (2D) cell cultures, three-dimensional (3D) multicellular spheroids, and organoids. They are essential tools for addressing complex biochemical questions. With continuous advancements in biological and cellular analysis technologies, in vitro cellular models designed to answer scientific questions have evolved rapidly. Early in vitro models primarily relied on 2D systems, which failed to accurately replicate the complex cellular compositions and microenvironmental interactions observed in vivo, let alone support sophisticated investigations into cellular biological functions. Subsequent improvements in cell culture techniques led to the development of 3D culture-based models, such as cellular spheroids. The advent of pluripotent stem cell technology further advanced the development of organoid systems, which closely mimic human organ development. Compared to traditional 2D models, both 3D cellular models and organoids offer significant advantages, including personalization and enhanced physiological relevance, making them particularly suitable for exploring molecular mechanisms of disease progression, discovering novel cellular and biomolecular functions, and conducting related studies. The imaging analysis of common cellular models primarily employs labeling-based methods for in situ imaging of targeted genes, proteins, and small-molecule metabolites, enabling further research on cell types, states, metabolism, and drug efficacy. However, these approaches have drawbacks such as poor labeling specificity and complex experimental procedures. By using cells as experimental models, mass spectrometry technology combined with morphological analysis can reveal quantitative changes and spatial distributions of various biological substances at the spatiotemporal level, including metabolites, proteins, lipids, peptides, drugs, environmental pollutants, and metals. This allows for the investigation of cell-cell interactions, tumor microenvironments, and cellular bioinformational heterogeneity. The application of these cutting-edge imaging technologies generates vast amounts of cellular data, necessitating the development of rapid, efficient, and highly accurate image data algorithms for precise segmentation and identification of single cells, multi-organelle structures, rare cell subpopulations, and complex cellular morphologies. A critical focus lies in creating deep learning models and algorithms that enhance the accuracy of cellular visualization. At the same time, establishing more robust data integration tools is essential not only for analyzing and interpreting outputs but also for effectively uncovering the biological significance of spatially resolved mass spectrometry data. Developing a cell imaging platform with high versatility, operational stability, and specificity to enable data interoperability will significantly enhance its utility in clinical research, thereby advancing investigations into disease molecular mechanisms and supporting precision diagnostics and therapeutics. In contrast to genomic, transcriptomic, and proteomic information, the metabolome can rapidly respond to external stimuli and cellular physiological changes within a short timeframe. This rapid and precise reflection of ongoing cellular state alterations has positioned spatial metabolomics as a pivotal approach for exploring the molecular mechanisms underlying physiological and pathological processes in cells, tissues, and organisms. In this review, we summarize research on cell imaging based on mass spectrometry technologies, including the selection and preparation of cell models, morphological analysis of cell models, spatial omics techniques based on mass spectrometry, mass cytometry, and their applications. We also discuss the current challenges and propose future directions for development in this field.

Tumorigenesis， invasion， and metastasis occur in the context of a persistent inflammatory microenvironment， and a variety of inflammatory factors can lead to the development of various tumors. Guided by the thought of "preventive treatment of disease" in TCM and the concept of tertiary prevention in modern medicine， it is of great significance to effectively intervene in the inflammatory stage of the disease， interrupt disease progression， prevent the occurrence of malignant tumors， and reverse the process of "inflammation-to-cancer transformation". Sinisan， a commonly used prescription in the Treatise on Febrile Diseases， has been widely applied in the treatment of precancerous lesions of the digestive system， demonstrating considerable advantages. This article reviewed literature from the past 20 years， summarizing the application of Sinisan in precancerous lesions of the digestive system from three aspects： the exploration of its prescription-syndrome relationship， clinical application， and mechanistic study. It is found that basic syndrome indications of Sinisan include harmonizing the Earth element to promote spleen-stomach transportation and transformation， soothing the liver and nourishing the Wood element to restore the smooth flow of Qi， and regulating Yin and Yang to relieve stagnation within the system. In clinical application， Sinisan has shown significant efficacy in atrophic gastritis and precancerous conditions such as intestinal metaplasia， gastric ulcer， ulcerative colitis， esophagitis， and pancreatitis. Mechanistic studies have revealed that Sinisan can inhibit inflammatory factors and improve the inflammatory microenvironment， inhibit cell proliferation and regulate apoptosis， exhibit anti-angiogenic and antitumorigenic effects， modulate immune function， and exert antioxidant effects. These mechanisms can be achieved by regulating pathways such as nuclear factor erythroid 2-related factor 2/heme oxygenase-1 （Nrf2/HO-1）， farnesoid X receptor （FXR）/Nrf2， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Takeda G protein-coupled receptor 5/cyclic adenosine monophosphate/protein kinase A （TGR5/cAMP/PKA）， interleukin-4/signal transducer and activator of transcription 6 （IL-4/STAT6）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， RhoA/Rho-associated protein kinase （RhoA/ROCK）， and transforming growth factor-β/Smad proteins （TGF-β/Smads）， confirming Sinisan's role in reversing the inflammation-to-cancer transformation. The current research status of Sinisan in precancerous lesions of the digestive system was thoroughly examined through the above three aspects， along with the identification of limitations and areas for improvement in current research. The aim is to provide a basis and support for future in-depth research on Sinisan， promote the development of new integrated treatment models combining TCM and Western medicine for precancerous lesions， and aid in the research and development of drugs related to precancerous lesions.

OBJECTIVE To investigate the improvement effects of 3，5，6，7，8，3′，4′-heptamethoxyflavone （HMF） of Fructus Aurantii on rats with damp blockage of the middle energizer. METHODS The rats were randomly divided into normal group， model group， positive control group （Raceanisodamine tablet， 1 mg/kg）， HMF low-dose， medium-dose and high-dose groups （0.3， 0.6， 0.9 mg/kg）， with 7 rats in each group. Except for the normal group， the other groups were modeled by internal and external composite factors. After successful modeling， the rats in each group were given the corresponding drug or normal saline， once a day， for 14 days. The general behavioral states such as dietary intake， water intake and mental state of the rats were observed， and the fecal water content rate and saliva flow rate were measured. Hematoxylin-eosin （HE） staining was used to observe the pathological and morphology in gastric and small intestinal tissues of rats. The plasma content of aldosterone was detected， and the expression of aquaporins （AQP3） in the gastric tissue of rats was determined. RESULTS Compared with the normal group， the dietary intake and water intake of the model group rats were significantly decreased （P＜0.01）， the fecal water content rate， salivary flow rate， plasma content of aldosterone and the expression of AQP3 in gastric tissue were increased significantly （P＜0.01）. Gastric tissue injury invaded the mucosal muscle layer， resulting in mucosal muscle layer rupture； pathological and morphological changes such as small intestinal villous erosion and glandular structure destruction were observed in the small intestine. Compared with the model group， the dietary intake and water intake of rats were increased in HMF groups； fecal water content rate， salivary flow rate， plasma content of aldosterone， the expression of AQP3 in gastric tissue were decreased， most of the above differences were statistically significant （P＜0.05 or P＜0.01）. The pathological and morphological changes in the gastric and small intestine tissues of rats had been improved to varying degrees. CONCLUSIONS HMF of Fructus Aurantii with dry property HMF could improve the symptoms of rats with damp blockage of middle energizer， the mechanism of which may be associated with reducing the content of plasma aldosterone and down-regulating the expression of gastric AQP3.

Objective:To investigate the correlation among physical activity,mild depressive symptoms and frontal alpha power asymmetry in college students.Methods:Seventy college students with mild depressive symp-toms who conformed to the standard of the Self-Rating Scale for Depression(SDS)of 53-62 and 70 normal col-lege students were recruited.The frontal alpha power was measured under quiet and closed-eye state,and the total physical activity(PA)was assessed with the International Physical Activity Questionnaire.Results:The college students with mild depressive symptoms had lower Total PA scores,right frontal alpha power and frontal alpha a-symmetry(FAA)than the normal controls(P＜0.001).In college students with mild depressive symptoms,the to-tal PA scores(r=-0.29,P＜0.05)and FAA(r=-0.41,P＜0.001)were negatively correlated with SDS scores,and the total PA scores were positively correlated with FAA(r=0.34,P＜0.01).Conclusion:The college students with mild depressive symptoms may have reduced physical activity and asymmetric right lateralization of frontal alpha power.There is a correlation among depressive symptoms,physical activity and frontal alpha power a-symmetry in college students with mild depressive symptoms.

Objective:To investigate the clinicopathological characteristics of early gastric cancer with mixed histological staging, and to analyze the prognostic effect of endoscopic submucosal dissection (ESD) for early gastric cancer.Methods:Clinical data of early gastric cancer patients treated with ESD in Gansu Wuwei Cancer Hospital from January 2011 to March 2020 were collected, and clinicopathological characteristics of patients with mixed-type early gastric cancer were analyzed by descriptive statistical methods. The clinical effects and influencing factors of ESD on early gastric cancer were analyzed by logistic regression. Kaplan-Meier was used to estimate the survival rate, and log-rank test was used to compare the survival rate.Results:A total of 269 patients (280 lesions) were included in this study, including 216 males (80.30%) and 53 females (19.70%), with age of 60.43±8.01 years. There were 25 lesions (8.93%) of mixed early gastric cancer, 248 lesions (88.57%) of differentiated early gastric cancer, and 7 lesions (2.50%) of undifferentiated early gastric cancer. Compared with differentiated and undifferentiated early gastric cancer, the lesion site of mixed early gastric cancer was mainly located in the upper 1/3 of the stomach [64.00% (16/25), 40.73% (101/248) VS 0.00% (0/7), χ2=10.211, P=0.006], the proportion of the lesion size ≤2 cm was relatively small [52.00% (13/25), 80.65% (200/248) VS 85.71% (6/7), χ2=11.173, P=0.004], and the proportion of infiltration depth in the mucosa was lower [52.00% (13/25), 85.48% (212/248) VS 57.14% (4/7), χ2=20.019, P<0.001], the proportion of positive vertical resection margin was relatively high [20.00% (5/25), 2.82% (7/248) VS 0.00% (0/7), χ2=16.657, P<0.001], the proportion of vascular invasion was higher than that of differentiated carcinoma but lower than that of undifferentiated carcinoma [36.00% (9/25), 2.42% (6/248) VS 42.86% (3/7), χ2=58.413, P<0.001], the complete resection rate was lower [76.00% (19/25), 93.15% (231/248) VS 100.00% (7/7), χ2=9.497, P=0.009], the curative resection rate was lower than that of differentiated early gastric cancer, but higher than that of undifferentiated early gastric cancer [48.00% (12/25), 89.52% (222/248) VS 42.86% (3/7), χ2=39.757, P<0.001], and the proportion of eCura grade C2 was higher than that of differentiated cancer, but lower than that of undifferentiated cancer [48.00% (12/25), 5.65% (14/248) VS 57.14% (4/7), χ2=58.766, P<0.001]. The results of multivariate analysis showed that the larger lesions ( P=0.004, OR=0.539, 95% CI: 0.354-0.822) was the risk factor for curative resection. In terms of infiltration depth, mucosal ( P=0.001, OR=51.799, 95% CI: 5.535-84.768) and submucosal 1 ( P<0.001, OR=29.301, 95% CI: 24.694-73.972) were protective factors for curative resection compared with submucosal 2. In terms of differentiation degree, compared with mixed type, differentiated type ( P=0.024, OR=3.947, 95% CI: 1.195-13.032) was the protective factor for curative resection, while undifferentiated type ( P=0.443, OR=0.424, 95% CI: 0.048-3.788) showed no difference between curative resection and mixed type. During the follow-up, 7 patients died. The overall survival time was 114.42±0.97 months, and the 5-year survival rate was 97.10%. There was no significant difference in the survival rate of early gastric cancer patients with different degrees of differentiation ( χ2=0.434, P=0.805). The survival rate of early gastric cancer patients with or without curative resection was significantly different ( χ2=4.081, P=0.043). Conclusion:Mixed early gastric cancer patients show high margin positive rate, vascular infiltration, and less curative resection than differentiated early gastric cancer. Therefore, the process of treating mixed early gastric cancer should be more rigorous. The long-term survival prognosis of early gastric cancer after ESD treatment is promising.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

BACKGROUND:For non-traumatic osteonecrosis of the femoral head,if the femoral head collapses,it will have a great impact on the normal life of the patients.Thus,it is necessary to use an appropriate way to evaluate the risk of femoral head collapse and then to take targeted measures to delay the process of femoral head collapse. OBJECTIVE:To analyze the natural course of early osteonecrosis of the femoral head(without collapse)under different locations of necrotic lesions. METHODS:121 patients(191 hips)with early non-traumatic osteonecrosis of the femoral head who were treated in the Outpatient Department of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2016 to October 2017 were enrolled in this study.The clinical data of all patients were followed up for 5 years to observe the collapse of osteonecrosis of the femoral head and the risk coefficient of femoral head collapse among different JIC types.The collapse rate of osteonecrosis of the femoral head was calculated during the follow-up. RESULTS AND CONCLUSION:(1)A total of 191 hips were included in this study.The femoral head collapsed in 86 hips during follow-up,with a total collapse rate of 45.0%.Among the influencing factors,age,ARCO stage and JIC classification were the main influencing factors of femoral head collapse(P<0.05),but body mass index,sex,incidence side and pathogenic factors were not the main influencing factors(P>0.05).(2)Among 191 hips,in JIC classification,the total collapse rates of type A,type B,type C1 and type C2 were 11.1%(2/18),30.2%(16/53),52.4%(43/82),and 65.8%(25/38),respectively.There were significant differences in the total collapse rate of the femoral head among all types(P<0.05).The collapse risk results showed that the collapse risk of type B,type C1 and type C2 was 2.41,5.22 and 7.89 times higher than that of type A,respectively.(3)Both JIC classification and ARCO stage were correlated with femoral head collapse(P<0.01).There was no significant difference in the collapse rate of the femoral head among all JIC types in ARCO I stage hips(P>0.05).In the hips with ARCO II stage,the collapse rates of the femoral head of JIC types A,B,C1 and C2 were 1.2%,19.5%,50.0%and 29.3%,respectively,and there were significant differences in the collapse rates among different types(P<0.05).(4)During follow-up,the collapse rates of the femoral head in the first to fifth years were 29.3%,7.9%,4.7%,2.6%and 0.5%,respectively.(5)Results showed that for early non-traumatic osteonecrosis of the femoral head,the risk of collapse of osteonecrosis of the femoral head is high within one year,and the location of the focus of osteonecrosis affects the risk of collapse of the femoral head.The effect of the location of the focus on the prognosis of the disease should be considered in clinical treatment.

BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

BACKGROUND:Osteonecrosis of the femoral head is one of the refractory diseases in orthopedic diseases.The natural collapse course of osteonecrosis of the femoral head under different stages and types affects the progression and prognosis of the disease. OBJECTIVE:To explore the progression of natural collapse within 5 years in patients under the different classifications of China-Japan Friendship Hospital(CJFH)with stage Ⅱ osteonecrosis of the International Association for Research Circulation Osseous(ARCO),and to analyze the collapse rate and collapse risk of the femoral head under the different classifications of CJFH. METHODS:A retrospective study was performed to select patients diagnosed with ARCO Ⅱ stage osteonecrosis of the femoral head without collapse in the Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2016 to October 2017.According to whether it collapsed,the number of hips was divided into the collapse group(n=82)and the non-collapsed group(n=70).The collapse risk of patients with osteonecrosis of the femoral head under different CJFH classifications,as well as the collapse time,number of collapses,and collapse rate within 5 years were counted,and then the Kaplan-Meier survival curve of the femoral head under different classification of CJFH was plotted. RESULTS AND CONCLUSION:(1)A total of 97 patients with 152 hips were enrolled,and 82 hips collapsed during the follow-up period,with a total collapse rate of 53.9%,of which the collapse rates of M type,C type,L1 type,L2 type,and L3 type were 0.0%,36.7%,51.4%,72.2%,and 77.8%,respectively,and the comparison between the groups was statistically significant(P<0.05).(2)In terms of collapse risk,the collapse risk of L1 type was 1.704 times that of C-type(P>0.05),while the collapse risks of L2 type and L3 type were 3.866 times and 6.423 times that of C type(P<0.05),respectively.(3)In terms of the Kaplan-Meier survival curve,the median survival time of the femoral head of ARCO Ⅱ stage patients was 3 years,with a 95%confidence interval of 2.885-3.471 years,and the survival rates of the femoral head at the first,third and fifth years were 65.1%(99/152),50.7%(77/152),and 46.1%(70/152),respectively.(4)These findings conclude that different CJFH classifications affect the collapse rate of ARCO Ⅱ stage osteonecrosis of the femoral head patients,among which L3 type patients have the highest collapse rate,followed by L2 type and L1 type patients;C type patients have a lower collapse rate,and M type patients do not collapse,which indicates that the preservation of the lateral column of the femoral head is of great significance for the natural collapse course of osteonecrosis of the femoral head.