OBJECTIVE To systematically analyze the population pharmacokinetics （PPK） studies of lacosamide and expound the influential factors of its pharmacokinetics in different populations. METHODS PPK studies of lacosamide were collected by searching the databases， such as Web of Science， PubMed， Embase， Metasearch， CNKI， Wanfang Data and VIP， both in Chinese and English. Relevant data were extracted， and the Prediction Model Risk of Bias Assessment Tool was used to evaluate the quality of the PPK models in the included studies. RESULTS Among 8 studies ultimately included， 6 were retrospective studies and 2 were prospective studies； 5 studies involved pediatric patients. Seven studies adopted a one-compartment model， while 1 study utilized a two-compartment model. Four studies had a model quality rating of grade A， two of grade B and two of grade C， respectively. Body weight， renal function， and hepatic enzyme inducers were significant covariates influencing PPK of lacosamide. CONCLUSIONS The existing PPK studies of lacosamide are predominantly conducted in pediatric populations. Pharmacokinetic variability is mainly influenced by body weight， renal function， and hepatic enzyme inducers. However， most PPK studies have not conducted external validation， and the generalizability of the models remains to be confirmed.

Objective To explore the epidemiological characteristics of gouty arthritis in Northwest China from 2023 to 2025, and to formulate preventive intervention measures. Methods By retrospectively analyzing the case data of medical institutions in Northwest China from January 2023 to June 2025 (a total of 8 139 cases), the incidence trend and population distribution characteristics of gouty arthritis in this area were analyzed. Multivariate logistic regression analysis was performed to identify risk factors. Results From 2023 to 2025, the prevalence rate of gouty arthritis in adult residents in Northwest China was 3.74% (304/8 139). Among the sites affected by gouty arthritis, the metatarsophalangeal joint accounted for the highest proportion (P<0.05). From the perspective of age distribution, the prevalence rate was the highest in 40-59 years old group (5.90%), followed by 66-80 years old group (4.21%) and >80 years old group (2.75%). The incidence rate in 40-65 years old group was higher than that in the other age groups (P<0.05). High blood uric acid and creatinine, alcohol drinking, obesity, high purine diet, concurrent chronic kidney disease and metabolic syndrome were risk factors affecting gouty arthritis in Northwest China (P<0.05). Conclusion High blood uric acid level, high creatinine level, alcohol drinking, obesity, high purine diet, concurrent chronic kidney disease and metabolic syndrome are risk factors influencing gouty arthritis in Northwest China. Based on the above factors, this study proposes comprehensive prevention strategies from the individual, community and public health levels to provide a scientific basis for reducing the incidence rate of gouty arthritis.

Immunoglobulin A nephropathy （IgAN） is the primary glomerulonephritis with the highest incidence rate in the world. It is also the main cause of end-stage renal disease （ESRD） in China， which has brought heavy economic burden to the society and patient families. Traditional Chinese medicine （TCM） has certain advantages in treating IgAN. In TCM， IgAN is classified into consumptive disease， hematuria， and edema categories， with the location in the kidney and involving the lung， liver， and spleen. Professor Ren Jixue， a master of TCM， believes that kidney deficiency and spleen deficiency are the root causes of IgAN， and the throat is the source of the disease. He proposed the theory of throat-kidney correlation and used the method of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat to treat IgAN， achieving significant therapeutic effects. Studies have shown that IgAN is closely related to mucosal immune defense. IgAN patients often experience recurrent and gradually worsening symptoms due to mucosal infections， and polymeric Ig receptor （PIgR） is an important component of mucosal defense function. The lack of PIgR leads to the accumulation of IgA molecules in the mucosal lamina propria， and the molecules enter the bloodstream in large quantities and ultimately deposit in the kidneys， causing kidney damage. Complement regulatory protein complement receptor type 1 （CR1） exists on red blood cells and glomeruli and has the function of inhibiting the activation and differentiation of B cells， clearing immune complexes， and inhibiting excessive activation of the complement system. Therefore， regulating the immune defense function through the mucosal-renal axis mediated by PIgR-CR1 will be an important target for preventing and treating IgAN. Based on the theory of throat-kidney correlation， this article explores the effects and molecular mechanisms of tonifying kidney and invigorating spleen as well as detoxifying and relieving sore-throat in preventing and treating IgAN by regulating the mucosal-kidney axis mediated by PIgR-CR1. It provides effective theoretical support and a scientific basis for TCM prevention and treatment of IgAN based on the theory of throat-kidney correlation.

OBJECTIVE To identify and characterize the chemical ingredients of Anchang formulation,further screen the active ingredients of this formulation treating ulcerative colitis by network pharmacology,and explore the potential targets and pathways,provi-ding scientific basis for its mechanism research and clinical application.METHODS Chemical ingredients in Anchang formulation were acquired by Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technology and literature retrieval.The potential active ingredients and key targets for the treatment were obtained from Swiss Target Prediction,GeneCards,STRING,and then Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were analyzed in the DAVID database.The interactions between the active ingredients and the core targets were verified by using the AutoDock software.The RAW 264.7 murine-derived macrophage inflammation model was also established to val-idate the anti-inflammatory activity of the pre-screened chemical ingredients and further explore the related mechanisms.RESULTS In this study,108 chemical ingredients of Anchang formulation were characterized by UPLC-Q-TOF-MS technology,and expanded to 134 through literature search.The component-target network where 39 core active components were screened was further constructed,and 15 key therapeutic targets were screened by the protein-protein interaction network constructed.The enrichment analysis of KEGG pathway indicated that Anchang formulation can regulate TNF,PI3K-Akt,MAPK,cancer and other related signaling pathways and ex-ert a therapeutic effect.The results of cell experiments showed that Anchang formulation and its active ingredients could inhibit the re-lease of NO,TNF-α and IL-6 in the LPS-induced RAW 264.7 cell inflammation model.CONCLUSION Based on the concept of"ingredient-target-pathway",this study evaluates the anti-inflammatory effect of Anchang formulation and its active ingredients,pre-dicts the potential mechanism of treatment for UC,and provides a theoretical basis and research ideas for the quality control of the for-mulation and its treatment for UC.

Objective To investigate the association between early peripheral perfusion index (PPI) and acute kidney injury (AKI) in patients admitted to the intensive care unit (ICU) following major noncardiac surgery. Methods This retrospective cohort study was conducted at a single center. Adult patients consecutively enrolled were those admitted to the ICU after major noncardiac surgery. PPI measurements were collected within the first 6 hours post-surgery. The primary outcome assessed was the occurrence of AKI within 7 days after surgery. Multivariate logistic regression analysis was employed to adjust for confounding factors,while receiver operating characteristic (ROC) curve analysis determined the most predictive cutoff PPI. Results The study included a total of 444 patients who underwent noncardiac surgery. The incidences of postoperative AKI and severe AKI were 9.23％ and 1.13％,respectively. Early postoperative PPI levels exhibited a skewed distribution,with a median value of 3.02 (2.02,4.24). After adjusting for various perioperative variables,PPI was found to be indepen-dently correlated with the occurrence of postoperative AKI (OR=0.734,95％ CI:0.580～0.930,P=0.010),as indicated by an area under the ROC curve of 0.6802 (95％ CI:0.6022～0.7582,P<0.001). Using a cutoff value of ≤ 2 .04 for PPI,the sensitivity and specificity for predicting postoperative AKI were determined to be approximately at 53.7％ and 77.2％ respectively. Further analysis revealed that patients with PPI ≤ 2.04 had a higher incidence of severe postoperative complications as well as prolonged mechanical ventilation duration and hospital stay. Conclusions A prompt reduction in postoperative PPI usage was found to be linked with the inci-dence of AKI occurring within 7 days following major noncardiac surgery.

Objective:To explore the mechanism by which governance mechanisms within the county medical community affect organizational collaboration.Methods:Based on institutional logic theory,this study analyzes the bureaucratic logic,market logic,and community logic within the county medical community,clarifies the administrative mechanisms,competitive mechanisms,relational mechanisms,and other governance mechanisms arising from different logics,and constructs a framework for the role of governance mechanisms in organizational collaborative behavior.Using 235 township health centers within the county medical communities across the country as a sample,the study employs path analysis to empirically test the mechanism framework for county-township collaboration and township-village collaboration models.Results:In the county-township collaboration model,there are a total of 7 pathways.Administrative mechanism and competitive mechanism directly influence collaborative behavior,while organizational interests and need cognition play a partial mediating role;organizational cognition fully mediates between relational mechanism and collaborative behavior.In the town-village collaboration model,there are a total of 4 pathways.Administrative mechanism and competitive mechanism directly influence collaborative behavior,with organizational interest cognition partially mediating between competitive mechanism and collaborative behavior;organizational interest cognition fully mediates between relational mechanism and collaborative behavior.Conclusions:Administrative mechanism serve as the foundation for organizational collaborative behavior;competitive mechanism have a significant negative impact on organizational collaborative behavior;relational mechanism are an important safeguard for organizational collaboration;enhancing organizational interests can directly enhance collaborative behavior.

Objective:To construct a machine learning classification prediction model using planning-omics (planomics) features to predict the γ pass rate of intensity-modulated radiotherapy (IMRT) plan dose verification in fixed-field thoracic tumors, and evaluate the application of planomics in radiotherapy quality assurance.Methods:The fixed-field IMRT plans of 240 patients with chest tumors admitted to Department of Radiotherapy, Henan Cancer Hospital from August 2022 to March 2023 were retrospectively analyzed. All plans underwent dose verification using the electronic portal imaging system detector on the Varian accelerator to collect field dose data. The dose verification results were analyzed through Portal Dosimetry in the treatment planning system of Eclipse. The γ pass rate standard was set at 2%/2 mm with a 10% dose threshold. From the planning documents, 48 conventional planning features, 2476 planomics features, and the combination of the previous two feature sets were extracted. Subsequently, an auto-encoder classification model was constructed. To evaluate the classification efficacy of various feature sets, 20 random train-test divisions were conducted by calculating the area under the receiver operating characteristic curve (AUC) values along with the accuracy rates.Results:After the feature selection, 2 conventional features and 16 planomics features were finally selected. In the testing set, the AUC values for the model using combined features, planomics features, and conventional planned features were 0.802±0.030, 0.740±0.069, and 0.673±0.083, respectively. In contrast, in the training set, these AUC values were 0.844±0.074, 0.816±0.047, and 0.687±0.036, respectively. The accuracy rates were 0.752±0.083, 0.703±0.110, and 0.648±0.081 in the testing set, and 0.753±0.098, 0.751±0.075, and 0.624±0.054 in the training set for the combined, planomics, and conventional planning feature sets, respectively.Conclusions:For thoracic fixed-field adjusted radiotherapy planning, the machine learning method based on planomics features can be utilized to build a classification model for predicting the γ pass rate. Combining planomics features with conventional planned features can enhance the predictive performance of the classification models.

Objective:To evaluate the detection capability of the contrast-enhanced three-dimensional turbo spin-echo (CE-SPACE) sequence for brain metastases (BM), aiming to provide evidence for precise target delineation in stereotactic radiotherapy (SRT).Methods:A total of 123 BM patients who received radiotherapy at the Affiliated Cancer Hospital of Zhengzhou University from May to November 2024 were enrolled. All patients underwent contrast-enhanced (CE) MRI and CT scans in the same treatment position, with images rigidly registered in the Eclipse planning system. Two experienced radiation oncologists independently delineated BM lesions on CE-MPRAGE and CE-SPACE sequences in a blinded manner. Patients were divided into the delayed group (10 min, n=61) and a priority group (5 min, n=62) based on the time interval between gadolinium injection and CE-SPACE acquisition. The non-parametric Wilcoxon rank-sum test was used to compare the lesion counts and volume differences between the two imaging sequences. Point-biserial correlation analysis was performed to assess the correlation between the additional lesions identified by CE-SPACE and lesion volume. Results:The overall analysis demonstrated that CE-SPACE detected 421 BM lesions, achieving an 8.2% higher detection rate than CE-MPRAGE ( Z=3.78, P<0.001). In terms of lesion volume, the median BM lesions volume identified by CE-SPACE [0.30(0.07,1.53)cm 3] was 8.7% larger than that by CE-MPRAGE [0.23 (0.04, 1.34) cm 3] ( Z=12.88, P<0.001). CE-SPACE demonstrated superior sensitivity for lesions ≤ 0.06 cm3, with negative correlation between the number of additional lesions detected and lesion volume ( r=-0.104, P=0.034). Subgroup analysis revealed that in the delayed group, CE-SPACE detected significantly more lesions [median 2 (1, 3.5) vs. 2 (1, 3), P=0.002] and larger volumes [0.39 (0.08, 2.24) cm3 vs. 0.29 (0.05, 1.99) cm3, P<0.001] than CE-MPRAGE. In the priority group, CE-SPACE detected significantly larger lesion volumes [0.55 (0.09, 2.06) cm3 vs. 0.45 (0.08, 1.88) cm3, P<0.001], but no significant difference was observed in lesion counts between two sequences ( P=0.059). Conclusions:Three-dimensional CE-SPACE sequence offers superior detection sensitivity for small BM (≤ 0.06 cm3), providing crucial guidance for accurate target delineation in SRT.

ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.

ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.