OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

ObjectiveTo analyze the research hotspots and development trends in the field of spinal cord stimulation (SCS) for spinal cord injury (SCI). MethodsLiterature about SCS for SCI was retrieve from the Web of Science (WOS) Core Collection database, with a time range from January, 1999 to July, 2025. VOSviewer 1.6.20 and CiteSpace 6.4.R2 were used to analyze the annual publication volume, countries, authors, institutions, journals and keywords. ResultsA total of 636 literatures were included. From 1999 to 2025, the overall publication trend in this field showed an upward trajectory, with recent years fluctuating but tending to stabilize. The country with the most publications was the United States (429 papers), followed by Russia (98 papers) and China (70 papers). The institution with the highest number of publications was the University of California, Los Angeles (76 papers), the author with the most publications was V. Reggie Edgerton (70 papers), and the journal with the most publications was Journal of Clinical Medicine (31 papers). The most frequently cited study focused on exploring the combination of epidural spinal cord stimulation with task-specific training to restore motor function in patients with complete SCI. Keyword analysis showed that the research hotspots in this field were mainly focused on neuroregulation mechanisms, recovery of motor and autonomic nervous dysfunction, artificial intelligence, closed-loop stimulation and brain-computer interface technology innovations. In recent years, the research focus gradually shifted from basic mechanisms to personalized and precise multifunctional rehabilitation strategies. ConclusionThe field of SCS for SCI has undergone phases of basic mechanism exploration and clinical application expansion. Current research hotspots and future trends focus primarily on the development of new stimulation paradigms and combined innovative technologies.

It is believed that patients with cirrhotic ascites exhibit a pathological mechanism characterized by the decline of healthy qi and the accumulation of pathogenic factors. Clinically， treatment should be based on the theory of tonification and purging， with a staged approach distinguishing between the active phase and the remission phase. The balance between tonification and purging should be adjusted according to the progression of pathogenic and healthy actors. In the acute phase， purging should take precedence over tonification， using purging as a means of tonification to facilitate the flow of water and qi through the triple energizer. The severity of water retention， dampness， blood stasis， and heat should be carefully assessed to ensure thorough elimination of pathogenic factors while avoiding harm to healthy qi. Medication adjustments should be made once the pathogenic factors are significantly weakened. In the remission phase， an integrated approach combining both tonification and purging should be adopted， incorporating purging within tonification to clear residual pathogens and prevent recurrence. Concurrently， proactive treatment of the underlying disease is essential to achieve complete recovery and prevent the recurrence of ascites.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Objective: To explore the longitudinal associations between dietary macronutrients and lung function in schoolaged children, so as to provide the nutritional research evidence for promoting children s lung health. Methods: In November 2021, two primary schools located in Chengdu, Sichuan Province were selected from the Southwest China Childhood Nutrition and Growth (SCCNG) cohort by a stratified cluster random sampling method, enrolling a total of 1 112 school aged children aged 8 to 13 years. At baseline, the dietary and sociodemographic characteristics of the children were assessed. One year later, the forced vital capacity (FVC) of the children was measured and converted into Z scores (FVC- Z ), while the vital capacity index (VCI) was also calculated. Generalized linear regression analysis was employed to examine the associations between dietary macronutrients and lung function, considering interactions with gender and age, followed by stratified analysis. Results: After adjusting for confounding factors, the analysis results of the generalized linear regression model showed that the carbohydrate energy ratio was negatively correlated with FVC- Z ( β =-0.02) and VCI ( β =-0.16), while the fat energy ratio showed a positive correlation with FVC- Z ( β =0.03) and VCI ( β =0.23) ( P <0.05). The protein energy ratio was positively correlated with FVC- Z ( β =0.09) and VCI ( β =0.60) specifically in girls ( P <0.05). Additionally, there was an interaction effect of age on the associations between macronutrients and lung function ( P <0.01); in children aged 8-9 and 10-11, the carbohydrate energy supply ratio was negatively correlated with FVC- Z ( β =-0.04, -0.03) and VCI ( β =-0.29, -0.21), and fat energy supply ratio was positively correlated with FVC- Z ( β =0.07, 0.05) and VCI ( β =0.46, 0.32) ( P <0.05). Conclusions There are age and sex differences in the association of dietary macronutrients with lung function, with a low carbohydrate, high fat diet promoting lung function in children. Additionally, protein intake appears to have a positive influence on the lung function of girls. The early school age period may represent a critical window for dietary interventions aimed at promoting lung health.

Atherosclerosis is a complex pathological condition resulting from lipid deposition， chronic inflammatory responses， and fibrosis， with a prolonged disease course and multifactorial etiology. Based on the traditional Chinese medicine （TCM） theory of accumulation syndrome， atherosclerosis can be classified under this category， with its pathogenesis involving phlegm， blood stasis， deficiency， and accumulation. This paper proposed a stage-based intervention strategy using the four therapeutic principles of "attacking， supplementing， dispersing， dissipating"， and divided into six stages based on the pathological progression， including the stage of accumulation before formation， the stage of accumulation already formed， the stage of nucleus accumulation， the stage of nucleus accumulation decay， the stage of nucleus accumulation consolidation， and the stage of severe stenosis of nucleus. At different stages， the intervention focuses on reinforcing healthy qi and consolidating the root， tonifying the kidneys and spleen， dispersing and removing turbidity， removing phlegm stagnation， promoting qi circulation， dispersing accumulations and removing stasis， attacking accumulation and expelling stasis， directing the turbid downward and dispersing accumulation， and treatment would be adjusted based on specific symptoms， which provides a theoretical framework for the prevention and treatment of atherosclerosis with TCM.

ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

The effects of different robust optimization parameters on the doses to organs-at-risk(OAR)and the clinical target volume(CTV)in proton therapy plans for localized prostate cancer are explored for identifying the optimal robust optimization parameters.A retrospective analysis is conducted on 10 cases in which proton plans with a total dose of 76 Gy delivered in 38 fractions are designed.In robust optimization,uncertainties of 3.5%in range and setup errors of 3,5 and 7 mm are considered.After being grouped by setup errors,3 groups of plans are obtained.The effects of setup errors on the doses to CTV and OAR are analyzed,and the robustness of the CTV dose is assessed,including the worst-case values of dosimetric parameters and the passing rates under different scenarios.The results show that as the setup error increased,the doses to OAR tended to rise.Compared with the 3 mm plan group,the 5 mm and 7 mm plan groups experience increases of 1.99%and 5.15%in rectal V70,3.71%and 10.01%in rectal V45,0.93%and 2.55%in bladder V70,and 1.71%and 5.27%in bladder V45,respectively;similar patterns are observed for the doses to sigmoid colon and bulbous urethra,and the differences are statistically significant(P<0.05).In robustness analysis,the CTV D99 in the 5 mm and 7 mm plan groups increases by 0.68 Gy and 0.95 Gy as compared with the 3 mm plan group,with passing rates improving by 7.2%and 9.6%,respectively(passing criterion:D95 receives at least 100%of the prescribed dose),with significant differences(P<0.05).Considering both OAR dose and CTV robustness,the setup error of 5 mm is found to be a reasonable choice for robust optimization in proton therapy plans for localized prostate cancer,as it can effectively balance the enhancement of CTV dose robustness with the control of dose escalation to OAR.

Peri-implant diseases have a relatively high incidence,and immune-inflammatory re-sponses are closely associated with peri-implant mucositis and peri-implantitis.The complement sys-tem is a vital component of the immune system.Its activation not only regulates the initiation and pro-gression of inflammatory responses but also plays a crucial role in bone remodeling.This review sum-marizes the roles of the core complement components C3 and C5 in various stages of bone remodeling after implant placement,as well as in peri-implant mucositis and peri-implantitis.The aim of the pa-per was to provide novel insights for the prevention and treatment of peri-implantitis through targeted regulation of complement protein levels.

Objective To investigate the causal relationship between gut microbiota and obstruc-tive sleep apnea syndrome(OSA)using a two-sample bidirectional Mendelian randomization(MR)approach.Methods Eligible single nucleotide polymorphisms(SNPs)were selected from genome-wide association study(GWAS)databases as instrumental variables.A bidirectional MR analysis was conducted to evaluate the causal effects between gut microbiota and OSA.Various statistical methods,including the inverse variance weighted(IVW)method,MR-Egger regression,the weighted model method,and the weighted median method,were employed for association assessment.The MR pleiot-ropy residual sum and outlier(MR-PRESSO)test,along with Cochran's Q test and the leave-one-out cross-validation method,were used to assess heterogeneity and pleiotropy.Results According to the IVW method analysis,an increased abundance of the genus Faecalibacterium(sp002397985)(OR=0.847,95％CI,0.719 to 0.997,P=0.046)was associated with a reduced risk of OSA.Conversely,increased abundances of the genera Bacteroides(OR=1.075,95％CI,1.016 to 1.138,P=0.012),Haemophilus(sp001679485)(OR=1.106,95％CI,1.016 to 1.203,P=0.021),Streptococcus(OR=1.168,95％CI,1.036 to 1.316,P=0.011),and Blautia(sp002159835)(OR=1.169,95％CI,1.035 to 1.319,P=0.012)were associated with an elevated risk of OSA.The reverse MR analysis revealed no significant association between the risk of OSA and the abundance of gut microbiota.The results of Cochran's Q test,MR-Egger test,and MR-PRESSO test indicated no het-erogeneity or horizontal pleiotropy(P＞0.05).Conclusion Causal relationships exist between the five genera(Faecalibacterium,Bacteroides,Haemophilus,Streptococcus,and Blautia)and the risk of OSA.