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.

ObjectiveTo optimize Tusizi prescription for ovarian reserve function based on the uniform design method combined with in vitro experiments and explore the underlying mechanisms of this prescription. MethodsThe uniform design method was adopted to design a 5-factor 11-level experiment on the water extract of Tusizi prescription. The cell-counting kit-8 （CCK-8） assay was employed to measure the viability of human ovarian granulosa cells （KGN cells） treated with Tusizi prescription extracts 1-11， and multivariate regression analysis was performed to determine the optimal herb ratio in this prescription. The potential targets of active ingredients in the prescription were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and encyclopedia of traditional Chinese medicine （ETCM）. The common targets shared by Tusizi prescription and diminished ovarian reserve （DOR） were selected and imported into search tool for the retrieval of interacting genes/proteins （STRING） to construct a protein-protein interaction （PPI） network and into gene function annotation database （DAVID） for gene ontology （GO） analysis. The CCK-8 assay was used to measure the viability of ovarian germline stem cells treated with hyperoside. The CCK-8 assay， 5-ethynyl-2'-deoxyuridine （EdU） staining， terminal-deoxynucleoitidyl transferase mediated nick-end labeling （TUNEL）， and enzyme-linked immunosorbent assay （ELISA） were employed to examine the proliferation， apoptosis， and estradiol （E₂） secretion of KGN cells treated with the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design. On this basis， the optimal prescription composition for maximizing the effect on ovarian reserve function was determined and preliminary insights into the underlying mechanisms of this prescription were gained. ResultsA total of 147 common targets were obtained from 278 targets of Tusizi prescription and 1 721 targets of DOR. GO analysis revealed 194 biological processes， primarily involving cellular responses to exogenous compound stimuli， negative regulation of apoptotic process， and positive regulation of cell proliferation. It identified 84 cellular components， including cell membrane， mitochondria， and neuronal cell body， as well as 144 molecular functions such as enzyme binding， estrogen response element binding， and nuclear estrogen receptor binding. The multivariate regression analysis revealed that when Tusizi prescription was composed of Cuscutae Semen， Lycii Fructus， Dioscoreae Rhizoma， Poria， and Nelumbinis Semen in a ratio of 27∶30∶17∶12∶14， the water extract of Tusizi prescription had the best effect of enhancing the viability of KGN cells. CCK-8 results showed that compared with the normal group， the hyperoside group demonstrated increased viability of ovarian germline stem cells （P<0.01）. The CCK-8， EdU， and ELISA results showed that compared with the normal group， the optimal prescription screened by uniform design and the water extract 11 of Tusizi prescription increased the proliferation and reduced the apoptosis of KGN cells （P<0.05， P<0.01）. ELISA results showed that compared with the normal group， the water extract 11 of Tusizi prescription promoted the E₂ secretion of KGN cells （P<0.05）， while the optimal prescription screened by uniform design had no significant effect on the E₂ secretion. ConclusionBoth the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 27∶30∶17∶12∶14） can improve the ovarian reserve function， and the former has better effect. Tusizi prescription can modulate biological processes （such as cell proliferation and apoptosis） and molecular functions （such as enzyme binding and estrogen response element binding） through active components like hyperoside to promote the proliferation and E₂ secretion and inhibit the apoptosis of KGN cells， thereby protecting the ovarian reserve function.

ObjectiveTo optimize Tusizi prescription for ovarian reserve function based on the uniform design method combined with in vitro experiments and explore the underlying mechanisms of this prescription. MethodsThe uniform design method was adopted to design a 5-factor 11-level experiment on the water extract of Tusizi prescription. The cell-counting kit-8 （CCK-8） assay was employed to measure the viability of human ovarian granulosa cells （KGN cells） treated with Tusizi prescription extracts 1-11， and multivariate regression analysis was performed to determine the optimal herb ratio in this prescription. The potential targets of active ingredients in the prescription were retrieved from traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP） and encyclopedia of traditional Chinese medicine （ETCM）. The common targets shared by Tusizi prescription and diminished ovarian reserve （DOR） were selected and imported into search tool for the retrieval of interacting genes/proteins （STRING） to construct a protein-protein interaction （PPI） network and into gene function annotation database （DAVID） for gene ontology （GO） analysis. The CCK-8 assay was used to measure the viability of ovarian germline stem cells treated with hyperoside. The CCK-8 assay， 5-ethynyl-2'-deoxyuridine （EdU） staining， terminal-deoxynucleoitidyl transferase mediated nick-end labeling （TUNEL）， and enzyme-linked immunosorbent assay （ELISA） were employed to examine the proliferation， apoptosis， and estradiol （E₂） secretion of KGN cells treated with the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design. On this basis， the optimal prescription composition for maximizing the effect on ovarian reserve function was determined and preliminary insights into the underlying mechanisms of this prescription were gained. ResultsA total of 147 common targets were obtained from 278 targets of Tusizi prescription and 1 721 targets of DOR. GO analysis revealed 194 biological processes， primarily involving cellular responses to exogenous compound stimuli， negative regulation of apoptotic process， and positive regulation of cell proliferation. It identified 84 cellular components， including cell membrane， mitochondria， and neuronal cell body， as well as 144 molecular functions such as enzyme binding， estrogen response element binding， and nuclear estrogen receptor binding. The multivariate regression analysis revealed that when Tusizi prescription was composed of Cuscutae Semen， Lycii Fructus， Dioscoreae Rhizoma， Poria， and Nelumbinis Semen in a ratio of 27∶30∶17∶12∶14， the water extract of Tusizi prescription had the best effect of enhancing the viability of KGN cells. CCK-8 results showed that compared with the normal group， the hyperoside group demonstrated increased viability of ovarian germline stem cells （P<0.01）. The CCK-8， EdU， and ELISA results showed that compared with the normal group， the optimal prescription screened by uniform design and the water extract 11 of Tusizi prescription increased the proliferation and reduced the apoptosis of KGN cells （P<0.05， P<0.01）. ELISA results showed that compared with the normal group， the water extract 11 of Tusizi prescription promoted the E₂ secretion of KGN cells （P<0.05）， while the optimal prescription screened by uniform design had no significant effect on the E₂ secretion. ConclusionBoth the water extract 11 of Tusizi prescription （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 4∶4∶2∶1∶1） and the optimal prescription screened by uniform design （Cuscutae Semen-Lycii Fructus-Dioscoreae Rhizoma-Poria-Nelumbinis Semen 27∶30∶17∶12∶14） can improve the ovarian reserve function， and the former has better effect. Tusizi prescription can modulate biological processes （such as cell proliferation and apoptosis） and molecular functions （such as enzyme binding and estrogen response element binding） through active components like hyperoside to promote the proliferation and E₂ secretion and inhibit the apoptosis of KGN cells， thereby protecting the ovarian reserve function.

Objective: To evaluate the comprehensive intervention effect of lunch for primary and secondary school students in Minhang District, so as to provide a theoretical and practical basis for lunch intervention in school. Methods: From October to December 2023, a convenience sampling method was used to select 1 937 students from one primary and secondary school in Minhang District.A comprehensive intervention measure focusing on "reducing oil and salt" for lunch recipe optimization and nutrition education was carried out, and a questionnaire survey was conducted to evaluate the intervention effect three months later. Chi square test and Wilcoxon rank test were used to compare the data before and after the intervention. Results: After intervention, the use of cooking oil and salt, the supply of protein and fat in primary and secondary school lunches were reduced, and had no obvious impact on energy and other major nutrients. After intervention, compared to before intervention, the proportion of primary school students who felt that lunch was greasy decreased (8.9%, 6.2%, χ 2=4.35), and the proportion of primary and secondary school students who felt that lunch were delicious decreased significantly (33.2%, 23.2%; 63.9%, 53.5%, χ 2=26.39, 17.52) ( P < 0.05 ). Secondary school students also felt reduced variety of food ingredients (46.9%, 38.3%, χ 2=16.05, P <0.05). In addition, after intervention, the total surplus rate of primary school students meals decreased (7.4%, 4.4%, χ 2=5.73), mainly reflected in the decrease of the surplus rate of staple foods (7.1%, 2.4%, χ 2=17.39), while the surplus rate of vegetable dishes increased ( 16.0 %, 21.2%, χ 2=6.01) ( P <0.05). Although there was no significant change in the total surplus rate of meals for secondary school students, the surplus rate of staple foods decreased (12.9%, 5.4%, χ 2=33.52), while the surplus rates of meat and vegetable dishes increased (11.2%, 26.9%; 17.5%, 33.2%, χ 2=74.26, 61.88) ( P <0.05). After intervention, there was no statistically significant difference in the overweight and obesity rates of primary school students ( χ 2=0.11,0.43) and secondary school students ( χ 2=0.01,0.00) compared to before intervention( P >0.05). After intervention, the lung capacity of primary school students [1 564 (1 269,1 890) mL] and sitting forward flexion [11.3 (7.6, 15.2) cm] increased compared to before intervention [1 522 (1 259, 1 819 ) mL, 10.5 (6.3, 13.5) cm] ( Z =2.20, 4.68, P <0.01), but there was no statistically significant difference in lung capacity and sitting forward flexion of secondary school students before and after intervention ( Z =-0.46, -0.08, P >0.05). Conclusion The comprehensive intervention of school lunch has promoted a significant decrease in the use of oil and salt in lunch and improved the quality of recipes, and has a positive impact on the situation of leftover lunch and the health of students to a certain extent.

Objective: To analyze the effects of health literacy on overweight and obesity among primary school students and their parents in terms of salt, oil and sugar reduction (referred to as the "three reductions"), so as to provide a theoretical basis for the development of obesity control measures. Methods: From March to April 2024, a total of 1 022 fourthgrade primary school students and 913 parents were surveyed in 24 classes in six counties in Shandong Province using multistage cluster random sampling, and physical measurements of primary school students were conducted. Pearsons correlation analysis and ordered multivariate Logistic regression were used to investigate the associations between health literacy of primary school students and their parents with overweight and obesity among children. Results: The detection rates of overweight and obesity primary school students in Shandong Province were 14.87% and 24.66%, respectively, with significant sex difference in obesity rate (29.46% for boys and 19.76% for girls) (χ2=12.93, P<0.01). In addition to students reducing oil scores, parental reducing salt,reducing oil,reducing sugar, comprehensive health literacy scores and students reducing salt,reducing sugar and comprehensive health literacy scores showed a negative relationship with students overweight and obesity (r=-0.10, -0.08, -0.07, -0.10, -0.04, -0.07, -0.03, P<0.05). The overweight and obesity rates among primary school students with high parental reducing salt,reducing oil,reducing sugar and composite health literacy scores were lower (OR=0.69, 0.69, 0.71, 0.63, P<0.05); and the overweight and obesity rate among students with high parental and low parental and high and low parental health literacy scores were lower (OR=0.68, 0.57, P<0.05). Conclusion Improving health literacy regarding "three reductions" for parents and children, especially parents, can effectively reduce the risk of childhood overweight and obesity.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

In recent years, there have been frequent adverse reactions/events associated with traditional Chinese medicine(TCM), especially liver injury related to traditional non-toxic TCM, which requires adequate attention. Liver injury related to traditional non-toxic TCM is characterized by its sporadic and insidious nature and is influenced by various factors, making its detection and identification challenging. There is an urgent need to develop a strategy and method for early detection and recognition of traditional non-toxic TCM-related liver injury. This study was based on national adverse drug reaction monitoring center big data, integrating methodologies such as reporting odds ratio(ROR), network toxicology, and computational chemistry, so as to systematically research the risk signal identification and evaluation methods for TCM-related liver injury. The optimized ROR method was used to discover potential TCM with a risk of liver injury, and network toxicology and computational chemistry were used to identify potentially high-risk TCM. Additionally, typical clinical cases were analyzed for confirmation. An integrated strategy of "discovery via big data, identification via dry/wet method, confirmation via typical cases, and precise risk prevention and control" was developed to identify the risk of TCM-related liver injury. Corydalis Rhizoma was identified as a TCM with high risk, and its toxicity-related substances and potential toxicity mechanisms were analyzed. The results revealed that liver injury is associated with components such as tetrahydropalmatine and tetrahydroberberine, with potential mechanisms related to immune-inflammatory pathways such as the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and Th17 cell differentiation. This paper innovatively integrated real-world evidence and computational toxicology methods, offering insights and technical support for establishing a risk discovery and identification strategy for TCM-related liver injury based on real-world big data, providing innovative ideas and strategies for guiding the safe and rational use of medication in clinical practices.
Corydalis/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Chemical and Drug Induced Liver Injury/etiology* ; Medicine, Chinese Traditional/adverse effects* ; Rhizome/adverse effects* ; Male ; Female

Baihuasheshecao(Hedyotis diffusa) is a commonly used traditional Chinese medicine derived from the whole herb of H. diffusa and has been widely utilized in folk medicine. It possesses anti-tumor, antibacterial, and anti-inflammatory properties, making it one of the frequently used herbs in TCM clinical practice. However, Shuixiancao(H. corymbosa) and Xianhuaercao(H. tenelliflora), species of the same genus, are often used as substitutes for Baihuasheshecao. To substantiate the medicinal basis of Baihuasheshecao, this study systematically reviewed classical herbal texts and modern literature, examining its nomenclature, botanical origin, harvesting, processing, properties, meridian tropism, pharmacological effects, and clinical applications. The results indicate that Baihuasheshecao was initially recorded as "Shuixiancao" in Preface to the Indexes to the Great Chinese Botany(Zhi Wu Ming Shi Tu Kao). Based on its morphological characteristics and habitat description, it was identified as H. diffusa in the Rubiaceae family. Subsequent records predominantly refer to it as Baihuasheshecao as its official name. In most regions, Baihuasheshecao is recognized as the authentic medicinal material, distinct from Shuixiancao and Xianhuaercao. Baihuasheshecao is harvested in late summer and early autumn, and the dried whole plant, including its roots, is used medicinally. The standard processing method involves cutting. It is known for its effects in clearing heat, removing toxins, reducing swelling and pain, and promoting diuresis to resolve abscesses. Initially, it was mainly used for treating appendicitis, intestinal abscesses, and venomous snake bites, and later, it became a treatment for cancer. The excavation of its clinical value followed a process in which overseas Chinese introduced the herb from Chinese folk medicine to other countries. After its unique anti-cancer effects were recognized abroad, it was reintroduced to China and gradually became a crucial TCM for cancer treatment. The findings of this study help clarify the historical and contemporary uses of Baihuasheshecao, providing literature support and a scientific basis for its rational development and precise clinical application.
Humans ; China ; Drugs, Chinese Herbal/chemistry* ; Hedyotis/classification* ; Medicine, Chinese Traditional/history*